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Tag: Autoimmune Diseases

  • Lifelong Drugs for Autoimmune Diseases Don’t Work Well. Now Scientists are Trying Something New

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    Scientists are trying a revolutionary new approach to treat rheumatoid arthritis, multiple sclerosis, lupus and other devastating autoimmune diseases — by reprogramming patients’ out-of-whack immune systems.

    When your body’s immune cells attack you instead of protecting you, today’s treatments tamp down the friendly fire but they don’t fix what’s causing it. Patients face a lifetime of pricey pills, shots or infusions with some serious side effects — and too often the drugs aren’t enough to keep their disease in check.

    “We’re entering a new era,” said Dr. Maximilian Konig, a rheumatologist at Johns Hopkins University who’s studying some of the possible new treatments. They offer “the chance to control disease in a way we’ve never seen before.”

    How? Researchers are altering dysfunctional immune systems, not just suppressing them, in a variety of ways that aim to be more potent and more precise than current therapies.

    They’re highly experimental and, because of potential side effects, so far largely restricted to patients who’ve exhausted today’s treatments. But people entering early-stage studies are grasping for hope.

    “What the heck is wrong with my body?” Mileydy Gonzalez, 35, of New York remembers crying, frustrated that nothing was helping her daily lupus pain.

    Diagnosed at 24, her disease was worsening, attacking her lungs and kidneys. Gonzalez had trouble breathing, needed help to stand and walk and couldn’t pick up her 3-year-old son when last July, her doctor at NYU Langone Health suggested the hospital’s study using a treatment adapted from cancer.

    Gonzalez had never heard of that CAR-T therapy but decided, “I’m going to trust you.” Over several months, she slowly regained energy and strength.

    “I can actually run, I can chase my kid,” said Gonzalez, who now is pain- and pill-free. “I had forgotten what it was to be me.”

    ‘Living drugs’ reset rogue immune systems

    CAR-T was developed to wipe out hard-to-treat blood cancers. But the cells that go bad in leukemias and lymphomas — immune cells called B cells — go awry in a different way in many autoimmune diseases.

    Some U.S. studies in mice suggested CAR-T therapy might help those diseases. Then in Germany, Dr. Georg Schett at the University of Erlangen-Nuremberg tried it with a severely ill young woman who had failed other lupus treatment. After one infusion, she’s been in remission — with no other medicine — since March 2021.

    Last month, Schett told a meeting of the American College of Rheumatology how his team gradually treated a few dozen more patients, with additional diseases such as myositis and scleroderma — and few relapses so far.

    Those early results were “shocking,” Hopkins’ Konig recalled.

    They led to an explosion of clinical trials testing CAR-T therapy in the U.S. and abroad for a growing list of autoimmune diseases.

    How it works: Immune soldiers called T cells are filtered out of a patient’s blood and sent to a lab, where they’re programmed to destroy their B cell relatives. After some chemotherapy to wipe out additional immune cells, millions of copies of those “living drugs” are infused back into the patient.

    While autoimmune drugs can target certain B cells, experts say they can’t get rid of those hidden deep in the body. CAR-T therapy targets both the problem B cells and healthy ones that might eventually run amok. Schett theorizes that the deep depletion reboots the immune system so when new B cells eventually form, they’re healthy.

    Other ways to reprogram rogue cells

    CAR-T is grueling, time consuming and costly, in part because it is customized. A CAR-T cancer treatment can cost $500,000. Now some companies are testing off-the-shelf versions, made in advance using cells from healthy donors.

    Another approach uses “peacekeeper” cells at the center of this year’s Nobel Prize. Regulatory T cells are a rare subset of T cells that tamp down inflammation and help hold back other cells that mistakenly attack healthy tissue. Some biotech companies are engineering cells from patients with rheumatoid arthritis and other diseases not to attack, like CAR-T does, but to calm autoimmune reactions.

    Scientists also are repurposing another cancer treatment, drugs called T cell engagers, that don’t require custom engineering. These lab-made antibodies act like a matchmaker. They redirect the body’s existing T cells to target antibody-producing B cells, said Erlangen’s Dr. Ricardo Grieshaber-Bouyer, who works with Schett and also studies possible alternatives to CAR-T.

    Last month, Grieshaber-Bouyer reported giving a course of one such drug, teclistamab, to 10 patients with a variety of diseases including Sjögren’s, myositis and systemic sclerosis. All but one improved significantly and six went into drug-free remission.

    Next-generation precision options

    Rather than wiping out swaths of the immune system, Hopkins’ Konig aims to get more precise, targeting “only that very small population of rogue cells that really causes the damage.”

    B cells have identifiers, like biological barcodes, showing they can produce faulty antibodies, Konig said. Researchers in his lab are trying to engineer T cell engagers that would only mark “bad” B cells for destruction, leaving healthy ones in place to fight infection.

    Nearby in another Hopkins lab, biomedical engineer Jordan Green is crafting a way for the immune system to reprogram itself with the help of instructions delivered by messenger RNA, or mRNA, the genetic code used in Covid-19 vaccines.

    In Green’s lab, a computer screen shines with brightly colored dots that resemble a galaxy. It’s a biological map that shows insulin-producing cells in the pancreas of a mouse. Red marks rogue T cells that destroy insulin production. Yellow indicates those peacemaker regulatory T cells — and they’re outnumbered.

    Green’s team aims to use that mRNA to instruct certain immune “generals” to curb the bad T cells and send in more peacemakers. They package the mRNA in biodegradable nanoparticles that can be injected like a drug. When the right immune cells get the messages, the hope is they’d “divide, divide, divide and make a whole army of healthy cells that then help treat the disease,” Green said.

    The researchers will know it’s working if that galaxy-like map shows less red and more yellow. Studies in people are still a few years away.

    Could you predict autoimmune diseases – and delay or prevent them?

    A drug for Type 1 diabetes “is forging the path,” said Dr. Kevin Deane at the University of Colorado Anschutz.

    Type 1 diabetes develops gradually, and blood tests can spot people who are brewing it. A course of the drug teplizumab is approved to delay the first symptoms, modulating rogue T cells and prolonging insulin production.

    Deane studies rheumatoid arthritis and hopes to find a similar way to block the joint-destroying disease.

    About 30 percent of people with a certain self-reactive antibody in their blood will eventually develop RA. A new study tracked some of those people for seven years, mapping immune changes leading to the disease long before joints become swollen or painful.

    Those changes are potential drug targets, Deane said. While researchers hunt possible compounds to test, he’s leading another study called StopRA: National to find and learn from more at-risk people.

    On all these fronts, there’s a tremendous amount of research left to do — and no guarantees. There are questions about CAR-T’s safety and how long its effects last, but it is furthest along in testing.

    Allie Rubin, 60, of Boca Raton, Florida, spent three decades battling lupus, including scary hospitalizations when it attacked her spinal cord. But she qualified for CAR-T when she also developed lymphoma — and while a serious side effect delayed her recovery, next month will mark two years without a sign of either cancer or lupus.

    “I just remember I woke up one day and thought, ‘Oh my god, I don’t feel sick anymore,’” she said.

    That kind of result has researchers optimistic.

    “We’ve never been closer to getting to — and we don’t like to say it — a potential cure,” said Hopkins’ Konig. “I think the next 10 years will dramatically change our field forever.”

    Copyright 2025. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

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    Associated Press

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  • 3 Nobel Prize Winners Discovered This Key Cause of Cancer

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    STOCKHOLM (AP) — Mary E. Brunkow, Fred Ramsdell and Dr. Shimon Sakaguchi won the Nobel Prize in medicine Monday for their discoveries concerning peripheral immune tolerance.

    Brunkow, 64, is a senior program manager at the Institute for Systems Biology in Seattle. Ramsdell, 64, is a scientific adviser for Sonoma Biotherapeutics in San Francisco. Sakaguchi, 74, is a distinguished professor at the Immunology Frontier Research Center at Osaka University in Japan.

    “Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases,” Olle Kämpe, chair of the Nobel Committee, said.

    The award, officially known as the Nobel Prize in Physiology or Medicine, is the first of the 2025 Nobel Prize announcements and was announced by a panel at the Karolinska Institute in Stockholm.

    The physics prize will be announced on Tuesday, chemistry on Wednesday and literature on Thursday. The Nobel Peace Prize will be announced Friday and the Nobel Memorial Prize in economics Oct. 13.

    The award ceremony will be Dec. 10, the anniversary of the death of Alfred Nobel, who founded the prizes. Nobel was a wealthy Swedish industrialist and the inventor of dynamite. He died in 1896.

    The trio will share prize money of 11 million Swedish kronor (nearly $1.2 million).

    The work that won the 2025 Nobel Prize in medicine

    The immune system has many overlapping systems to detect and fight bacteria, viruses and other intruders. Key immune warriors such as T cells get trained on how to spot bad actors. If some instead go awry in a way that might trigger autoimmune diseases, they’re supposed to be eliminated in the thymus — a process called central tolerance.

    The Nobel winners unraveled an additional way the body keeps the system in check.

    The Nobel Committee said it started with Sakaguchi’s discovery in 1995 of a previously unknown T cell subtype now known as regulatory T cells or T-regs.

    Then in 2001, Brunkow and Ramsdell discovered a culprit mutation in a gene named Foxp3, a gene that also plays a role in a rare human autoimmune disease.
    Brunkow said she and Ramsdell were working together at a biotech company, investigating why a particular strain of mice had an over-active immune system.

    They had to work with brand-new techniques to find the mouse gene behind the problem — but quickly realized it could be a major player in human health, too.
    “From a DNA level, it was a really small alteration that caused this massive change to how the immune system works,” she told AP.

    Two years later, Sakaguchi linked the discoveries to show that the Foxp3 gene controls the development of those T-regs — which in turn act as a security guard to find and curb other forms of T cells that overreact.

    Why this work matters

    The work opened a new field of immunology, said Karolinska Institute rheumatology professor Marie Wahren-Herlenius. Researchers around the world now are working to use regulatory T cells to develop treatments for autoimmune diseases and cancer.

    Dr. Jonathan Schneck, a pathology professor at Johns Hopkins University, is among those who study T cells. He said that until the trio’s research published, immunologists didn’t understand the complexity of how the body differentiates foreign cells from its own and how it can tamp down an overreaction.

    The discoveries haven’t yet led to new therapies, Schneck cautioned. But “it’s incredibly important to emphasize, this work started back in 1995 and we’re reaping the benefits but yet have many more benefits we can reap” as scientists build on their work.

    How Mary E. Brunkow, Fred Ramsdell and Dr. Shimon Sakaguchi reacted

    Thomas Perlmann, secretary-general of the Nobel Committee, said he was only able to reach Sakaguchi by phone Monday morning.

    “I got hold of him at his lab and he sounded incredibly grateful, expressed that it was a fantastic honor. He was quite taken by the news,” Perlmann said. He added that he left voicemails for Brunkow and Ramsdell.

    At a news conference hours later, Sakaguchi called his win “a happy surprise.” He said he expected he’d have to wait a bit longer until the research makes more contributions in clinical science.

    In the beginning, he said the area of his research was not very popular and he had to struggle at times to earn research funding. But there were other scientists who were also interested in the same area of research and their cooperation led to the achievement, he said, thanking his fellow researchers.

    “There are many illnesses that need further research and treatment, and I hope there will be further progress in those areas so that findings will lead to prevention of diseases. That’s what our research is for,” he said.

    Sakaguchi’s news conference was interrupted by a call from Japanese Prime Minister Shigeru Ishiba, who congratulated the scientist and asked him about the time frame for the research to be clinically applied to, for example, cancer treatment.

    “Hopefully we can reach that stage in about 20 years, though I’m not sure if will still be around,” Sakaguchi told the prime minister. “But science will advance and by that time cancer will no longer be scary but treatable.”

    Brunkow, meanwhile, got the news of her prize from an AP photographer who came to her Seattle home in the early hours of the morning.

    She said she had ignored the earlier call from the Nobel Committee. “My phone rang and I saw a number from Sweden and thought: ‘That’s just, that’s spam of some sort.’”

    “When I told Mary she won, she said, ‘Don’t be ridiculous,’” said her husband, Ross Colquhoun.

    The AP could not immediately reach Ramsdell.

    Wasson reported from Seattle and Neergaard from Washington. Mari Yamaguchi in Tokyo and Stefanie Dazio and David Keyton in Berlin contributed.

    AP Nobel Prizes: https://apnews.com/hub/nobel-prizes

     Copyright 2025. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

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    Associated Press

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  • Trio Wins Nobel Prize in Medicine for Discoveries on Immune System

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    Immunologists Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi were awarded the Nobel Prize in Physiology or Medicine for discoveries that spurred the development of new treatments for cancer and autoimmune diseases and laid the foundation for a new field of research.

    The trio identified a core feature of how the immune system functions and keeps itself in-check: regulatory T-cells. They prevent other immune cells from attacking our own bodies and developing autoimmune conditions including Type 1 diabetes and rheumatoid arthritis. Based on this fundamental knowledge, clinical trials are ongoing to test therapies for autoimmune diseases, cancer and following organ transplantation.

    Copyright ©2025 Dow Jones & Company, Inc. All Rights Reserved. 87990cbe856818d5eddac44c7b1cdeb8

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    Brianna Abbott

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  • Treating Hashimoto’s Disease (Hypothyroidism) Naturally with Diet  | NutritionFacts.org

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    What were the results of a randomized, double-blind, placebo-controlled trial of a daily half teaspoon of powdered black cumin in Hashimoto’s patients?

    “Autoimmune thyroiditis, also known as Hashimoto’s thyroiditis, is an organ-specific autoimmune disorder,” where our body attacks our own thyroid gland, often leading to hypothyroidism due to destruction and scarring of the gland itself. We know there’s a genetic component, since identical twins are more likely to share the disease than fraternal twins. “However, even with identical twins, the concordance rate was only about 50%, emphasizing that important factors such as the environment play a role in disease pathogenesis.” Indeed, even if your identical twin, who has basically your exact same DNA, has the disease, there’s only like a flip of a coin’s chance you’ll get it. Genes load the gun, but the environment may pull the trigger.

    More than 90 synthetic chemicals were noted to show disruption of hormonal balance or thyroid dysfunction.” However, only a few such ‘pollutants show evidence that they contribute to autoimmune thyroid disease.” These include polyaromatic hydrocarbons. Smokers get a lot of them from cigarettes, but in nonsmokers, exposure comes almost entirely from food, as you can see below and at 1:18 in my video Diet for Hypothyroidism: A Natural Treatment for Hashimoto’s Disease. 

    Polycyclic aromatic hydrocarbons are primarily formed when muscle meats, such as beef, pork, fish, or chicken, are cooked using high-temperature methods, such as grilling. PBBs, polybrominated biphenols, are a type of flame-retardant chemical no longer manufactured in the United States, but are still found in the aquatic food chain. PCBs, polychlorinated biphenols, are used in a number of industrial processes and end up in people’s bodies, again, largely through the consumption of fish, but also eggs and other meats, as seen here and at 1:41 in my video.

    So, one might suspect those eating plant-based diets would have lower rates of hypothyroidism, and, indeed, despite their lower iodine intake, vegan diets tended to be protective. But they’ve never been put to the test in an interventional trial. A modification of the Paleolithic diet has been tried in Hashimoto’s patients, but it didn’t appear to improve thyroid function. What did, though, is Nigella Sativa. That name should sound familiar to anyone who’s read my book How Not to Diet or watched my live Evidence-Based Weight Loss presentation. Nigella Sativa is the scientific name for black cumin, which is just a simple spice that’s also used for a variety of medicinal purposes.

    In one study, Hashimoto’s patients received a half teaspoon of powdered black cumin every day for eight weeks in a randomized, double-blind, placebo-controlled trial. Not only was there a significant reduction in body weight, which is why I profiled it in my book, but the black cumin also significantly reduced the thyroid-stimulating hormone, a sign that thyroid function was improving. It even lowered the level of autoimmune anti-thyroid antibodies, as well as increased blood levels of thyroid hormone T3 in these Hashimoto’s patients. In addition, there was a significant drop in Interleukin 23, a proinflammatory cell signal thought to help promote the autoimmune inflammation of the thyroid, which “further confirms the anti-inflammatory nature of the plant.” And what were the side effects? There was a 17 percent drop in “bad” LDL cholesterol, as shown below and at 3:19 in my video.

    Given the fact that patients with Hashimoto’s may be at particularly high risk of developing heart disease, this is exactly the kind of side effects we’d want. “Considering these health-promoting effects of N. Sativa [black cumin], it can be considered as a therapeutic approach in the management of Hashimoto-related metabolic abnormalities.”

    A similar trial failed to find a benefit, though. Same dose, same time frame, but no significant changes in thyroid function. In contrast with the previous study, though, the study participants were not all Hashimoto’s patients, but rather hypothyroid for any reason, and that may have diluted the results. And it’s possible that telling patients to take the black cumin doses with their thyroid hormone replacement therapy may have interfered with its absorption, which is an issue similar to other foods and drugs, and why patients are normally told to take it on an empty stomach. Since there are no downsides—it’s just a simple spice—I figure, why not give it a try? The worst that can happen is you’ll have tastier food.

    Doctor’s Note:

    I get a lot of questions about thyroid function, and I am glad to have been able to do this series. If you missed any of the other videos, see the related posts below.

    For more on black cumin, see my book How Not to Diet and my presentation Evidence-Based Weight Loss. 

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    Michael Greger M.D. FACLM

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  • Eating with Hypothyroidism and Hyperthyroidism  | NutritionFacts.org

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    Is the apparent protection of plant-based diets for thyroid health due to the exclusion of animal foods, the benefits of plant foods, or both?

    Several autoimmune diseases affect the thyroid gland, and Graves’ disease and Hashimoto’s thyroiditis are the most common. Graves’ disease results in hyperthyroidism, an overactive thyroid gland. Though slaughter plants are supposed to remove animals’ thyroid glands as they “shall not be used for human food,” should some neck meat slip in, you can suffer a similar syndrome called Hamburger thyrotoxicosis. That isn’t from your body making too much thyroid hormone, though. Rather, it’s from your body eating too much thyroid hormone. Graves’ disease is much more common, and meat-free diets may be able to help with both diseases, as plant-based diets may be associated with a low prevalence of autoimmune disease in general, as observed, for example, in rural sub-Saharan Africa. Maybe it’s because plants are packed with “high amounts of antioxidants, possible protective factors against autoimmune disease,” or because they’re packed with anti-inflammatory compounds. After all, “consuming whole, plant-based foods is synonymous with an anti-inflammatory diet.” But you don’t know until you put it to the test.

    It turns out that the “exclusion of all animal foods was associated with half the prevalence of hyperthyroidism compared with omnivorous diets. Lacto-ovo [dairy-and-egg] and pesco [fish] vegetarian diets were associated with intermediate protection.” But, for those eating strictly plant-based, there is a 52 percent lower odds of hyperthyroidism.

    As I discuss in my video The Best Diet for Hypothyroidism and Hyperthyroidism, this apparent protection “may be due to the exclusion of animal foods, the [beneficial] effects of plant foods, or both. Animal foods like meat, eggs, and dairy products may contain high oestrogen concentrations, which have been linked to autoimmunity in cell and animal studies.” Or it could be because the decrease in animal protein by excluding animal foods may downregulate IGF-1, which is not just a cancer-promoting growth hormone, but may play a role in autoimmune diseases. The protection could also come from the goodness in plants that may “protect cells against autoimmune processes,” like the polyphenol phytochemicals, such as flavonoids found in plant foods. Maybe it’s because environmental toxins build up in the food chain. For example, fish contaminated with industrial pollutants, like PCBs, are associated with an increased frequency of thyroid disorders.

    But what about the other autoimmune thyroid disease, Hashimoto’s thyroiditis, which, assuming you’re getting enough iodine, is the primary cause of hypothyroidism, an underactive thyroid gland? Graves’ disease wasn’t the only autoimmune disorder that was rare or virtually unknown among those living in rural sub-Saharan Africa, eating near-vegan diets. They also appeared to have less Hashimoto’s.

    There is evidence that those with Hashimoto’s have compromised antioxidant status, but we don’t know if it’s cause or effect. But if you look at the dietary factors associated with blood levels of autoimmune anti-thyroid antibodies, animal fats seem to be associated with higher levels, whereas vegetables and other plant foods are associated with lower levels. So, again, anti-inflammatory diets may be useful. It’s no surprise, as Hashimoto’s is an inflammatory disease—that’s what thyroiditis means: inflammation of the thyroid gland.

    Another possibility is the reduction in intake of methionine, an amino acid concentrated in animal protein, thought to be one reason why “regular consumption of whole-food vegan diets is likely to have a favourable influence on longevity through decreasing the risk of cancer, coronary [heart] disease, and diabetes.” Methionine restriction improves thyroid function in mice, but it has yet to be put to the test for Hashimoto’s in humans.

    If you compare the poop of patients with Hashimoto’s to controls, the condition appears to be related to a clear reduction in the concentration of Prevotella species. Prevotella are good fiber-eating bugs known to enhance anti-inflammatory activities. Decreased Prevotella levels are also something you see in other autoimmune conditions, such as multiple sclerosis and type 1 diabetes. How do you get more Prevotella? Eat more plants. If a vegetarian goes on a diet of meat, eggs, and dairy, within as few as four days, their levels can drop. So, one would expect those eating plant-based diets to have less Hashimoto’s, but in a previous video, I expressed concern about insufficient iodine intake, which could also lead to hypothyroidism. So, which is it? Let’s find out.

    “In conclusion, a vegan diet tended to be associated with lower, not higher, risk of hypothyroid disease.” Why “tended”? The associated protection against hypothyroidism incidence and prevalence studies did not reach statistical significance. It wasn’t just because they were slimmer either. The lower risk existed even after controlling for body weight. So, researchers think it might be because animal products may induce inflammation. The question I have is: If someone who already has Hashimoto’s, what happens if they change their diet? That’s exactly what I’ll explore next.

    This is the third in a four-video series on thyroid function. The first two were Are Vegans at Risk for Iodine Deficiency? and Friday Favorites: The Healthiest Natural Source of Iodine.

    Stay tuned for the final video: Diet for Hypothyroidism: A Natural Treatment for Hashimoto’s Disease. 

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    Michael Greger M.D. FACLM

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  • Treat Type 1 Diabetes with a Plant-Based Diet?  | NutritionFacts.org

    Treat Type 1 Diabetes with a Plant-Based Diet?  | NutritionFacts.org

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    Is it possible to reverse type 1 diabetes if caught early enough?

    The International Journal of Disease Reversal and Prevention has already had its share of miraculous disease reversals with a plant-based diet. For instance, one patient began following a whole food, plant-based diet after having two heart attacks in two months. Within months, he experienced no more chest pain, controlled his cholesterol, blood pressure, and blood sugars, and also lost 50 pounds as a nice bonus. Yet, the numbers “do not capture the patient’s transformation from feeling like a ‘dead man walking’ to being in command of his health with a new future and life.” 

    I’ve previously discussed cases of reversing the autoimmune inflammatory disease psoriasis and also talked about lupus nephritis (kidney inflammation). What about type 1 diabetes, an autoimmune disease we didn’t think we could do anything about? In contrast to type 2 diabetes, which is a lifestyle disease that can be prevented and reversed with a healthy enough diet and lifestyle, type 1 diabetes is an autoimmune disease in which our body attacks our pancreas, killing off our insulin-producing cells and condemning us to a life of insulin injections—unless, perhaps, it’s caught early enough. If a healthy enough diet is started early enough, might we be able to reverse the course of type 1 diabetes by blunting that autoimmune inflammation?

    As I discuss in my video Type 1 Diabetes Treatment: A Plant-Based Diet, we know that patients with type 1 diabetes “may be able to reduce insulin requirements and achieve better glycemic [blood sugar] control” with healthier diets. For example, children and teens were randomized to a nutritional intervention in which they increased the whole plant food density of their diet—meaning they ate more whole grains, whole fruits, vegetables, legumes (beans, split peas, chickpeas, and lentils), nuts, and seeds. Researchers found that the more whole plant foods, the better the blood sugar control.

    The fact that more whole fruits were associated “with better glycemic [blood sugar] control has important clinical implications for nutrition education” in those with type 1 diabetes. We should be “educating them on the benefits of fruit intake, and allaying erroneous concerns that fruit may adversely affect blood sugar.”

    The case series in the IJDRP, however, went beyond proposing better control of just their high blood sugars, the symptom of diabetes, but better control of the disease itself, suggesting the anti-inflammatory effects of whole healthy plant foods “may slow or prevent further destruction of the beta cells”—the insulin-producing cells of the pancreas—“if dietary intervention is initiated early enough.” Where did this concept come from?

    A young patient. Immediately following diagnosis of type 1 diabetes at age three, a patient began a vegetable-rich diet and, three years later, “has not yet required insulin therapy…and has experienced a steady decline in autoantibody levels,” which are markers of insulin cell destruction. Another child, who also started eating a healthier diet, but not until several months after diagnosis, maintains a low dose of insulin with good control. And, even if their insulin-producing cells have been utterly destroyed, individuals with type 1 diabetes can still enjoy “dramatically reduced insulin requirements,” reduced inflammation, and reduced cardiovascular risk, which is their number one cause of death over the age of 30. People with type 1 diabetes have 11 to 14 times the risk of death from cardiovascular disease compared to the general population, and it’s already the top killer among the public, so it’s closer to 11 to 14 times more important for those with type 1 diabetes to be on the only diet and lifestyle program ever proven to reverse heart disease in the majority of patients—one centered around whole plant foods. The fact it may also help control the disease itself is just sugar-free icing on the cake.

    All this exciting new research was presented in the first issue of The International Journal of Disease Reversal and Prevention. As a bonus, there’s a companion publication called the Disease Reversal and Prevention Digest. These are for the lay public and are developed with the belief I wholeheartedly share that “everyone has a right to understand the science that could impact their health.” You can go behind the scenes and hear directly from the author of the lupus series, read interviews from luminaries like Dean Ornish, see practical tips from dietitians on making the transition towards a healthier diet, and enjoy recipes. 

    The second issue includes more practical tips, such as how to eat plant-based on a budget, and gives updates on what Dr. Klaper is doing to educate medical students, what Audrey Sanchez from Balanced is doing to help change school lunches, and how Dr. Ostfeld got healthy foods served in a hospital. (What a concept!) And what magazine would be complete without an article to improve your sex life? 

    The journal is free, downloadable at IJDRP.org, and its companion digest, available at diseasereversaldigest.com, carries a subscription fee. I am a proud subscriber.

    Want to learn more about preventing type 1 diabetes in the first place? See the related posts below.

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    Michael Greger M.D. FACLM

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  • Eating an Anti-Inflammatory Diet for Lupus  | NutritionFacts.org

    Eating an Anti-Inflammatory Diet for Lupus  | NutritionFacts.org

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    Green smoothies are put to the test for the autoimmune disease lupus.

    There are dozens and dozens of journals I try to stay on top of every month, and one I always anticipate is The International Journal of Disease Reversal and Prevention, a peer-reviewed medical “journal created to document the science of nutrition and lifestyle to prevent, suspend and reverse disease,” with an editor-in-chief no less prestigious than Dr. Kim Williams, past president of the American College of Cardiology. I was honored to join its editorial advisory board, along with so many of my heroes. The best part? It’s free. Go to IJDRP.org and put in your email to subscribe at no cost, and you’ll be alerted when new issues are out, which you can download in full in PDF form. (Did I mention it’s free?)

    When it comes to chronic lifestyle diseases, wrote Dr. Williams, “Instead of preventing chronic lifestyle diseases, we [doctors] manage. Never cure, just mitigate. Why? Because of finance, culture, habit, and tradition.” There are many of us, though, who “envision a world where trillions of dollars are not spent on medical care that should never have been necessary, but rather on infrastructure, environment, education, and advancing science. For this reason, comes The International Journal of Disease Reversal and Prevention (IJDRP).” After all, wrote the journal’s co-founder, “Without data, you’re just another person with an opinion.”

    To give you a taste of the journal: How about pitting plants against one of the most inflammatory diseases out there—lupus, an autoimmune disease in which your body can start attacking your DNA? Kidney inflammation is a common consequence, and even with our armamentarium of immunosuppressant drugs and steroids, lupus-induced kidney inflammation can lead to end-stage renal disease, which means dialysis, and even death. That is, unless you pack your diet with some of the most anti-inflammatory foods out there and your kidney function improves so much you no longer need dialysis or a kidney transplant. Another similar case was presented with a resolution in symptoms and normal kidney function, unless the patient deviated from the diet and his symptoms then reappeared.

    As I discuss in my video Anti-Inflammatory Diet for Lupus, even just cutting out animal products can make a difference. Researchers randomized people to remove meat, eggs, and dairy from their diets without significantly increasing fruit and vegetable intake and found that doing just that can lower C-reactive protein levels by nearly a third within eight weeks, as you can see below and at 2:21 in my video. (Our C-reactive protein level is a sensitive indicator of whole-body inflammation.)

    But with lupus, the researchers didn’t mess around. Each day, the study subjects were to eat a pound of leafy greens and cruciferous vegetables like kale, fruits like berries, and lots of chia or flax, and drink a gallon of water. We’re talking about a green smoothie diet to extinguish lupus flares. (Note, though, that if your kidneys are already compromised, this should be done under physician supervision so they can monitor your electrolytes like potassium and make sure you don’t get overloaded with fluid.) Bottom line? With such remarkable improvements due to dietary changes alone, the hope is that researchers will take up the mantle and formally put it to the test. 

    Reversals of autoimmune inflammatory skin disease can be particularly striking visually. A woman with a 35-year history of psoriasis that had been unsuccessfully managed for 19 years with drugs suffered from other autoimmune conditions, including Sjogren’s syndrome. She was put on an extraordinarily healthy diet packed with greens and other vegetables, fruits, nuts, seeds, avocados, and some whole grains, and boom! Within one year, she went from 40 percent of her entire body surface area inflamed and affected down to 0 percent, completely clear, and, as a bonus, her Sjogren’s symptoms resolved, too, while helping to normalize her weight and cholesterol. You can see before and after photos below and at 3:39 in my video. 

    I think I only have one other video on lupus: Fighting Lupus with Turmeric: Good as Gold. It’s not for lack of trying, though. There just hasn’t been much research out there.

    I talk about another autoimmune disease, type 1 diabetes, in Type 1 Diabetes Treatment: A Plant-Based Diet.

    To read and subscribe—for free—to The International Journal of Disease Reversal and Prevention, visit www.IJDRP.org.

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    Michael Greger M.D. FACLM

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  • The Largest Study on Fasting in the World  | NutritionFacts.org

    The Largest Study on Fasting in the World  | NutritionFacts.org

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    The Buchinger-modified fasting program is put to the test.

    A century ago, fasting—“starvation, as a therapeutic measure”—was described as “the ideal measure for the human hog…” (Fat shaming is not a new invention in the medical literature.) I’ve covered fasting for weight loss extensively in a nine-video series, but what about all the other purported benefits? I also have a video series on fasting for hypertension, but what about psoriasis, eczema, type 2 diabetes, lupus, metabolic disorder, rheumatoid arthritis, other autoimmune disorders, depression, and anxiety? Why hasn’t it been tested more?

    One difficulty with fasting research is: What do you mean by fasting? When I think of fasting, I think of water-only fasting, but, in Europe, they tend to practice “modified therapeutic fasting,” also known as Buchinger fasting, which is more like a very low-calorie juice fasting with some vegetable broth. Some forms of fasting may not even cut calories at all. As you can see below and at 1:09 in my video The World’s Largest Fasting Study, Ramadan fasting, for example, is when devout Muslims abstain from food and drink from sunrise to sunset, yet, interestingly, they end up eating the same amount—or even more food—overall.

    The largest study on fasting to date was published in 2019. More than a thousand individuals were put through a modified fast, cutting daily intake down to about ten cups of water, a cup of fruit juice, and a cup of vegetable soup. They reported very few side effects. In contrast, the latest water-only fasting data from a study that involved half as many people reported nearly 6,000 adverse effects. Now, the modified fasting study did seem to try to undercount adverse effects by only counting reported symptoms if they were repeated three times. However, adverse effects like nausea, feeling faint, upset stomach, vomiting, or palpitations were “observed only in single cases,” whereas the water-only fasting study reported about 100 to 200 of each, as you can see below and at 2:05 in my video. What about the benefits though?

    In the modified fasting study, participants self-reported improvements in physical and emotional well-being, along with a surprising lack of hunger. What’s more, the vast majority of those who came in with a pre-existing health complaint reported feeling better, with less than 10 percent stating that their condition worsened, as you can see in the graph below and at 2:24 in my video. 

    However, the study participants didn’t just fast; they also engaged in a lifestyle program, which included being on a plant-based diet before and after the modified fast. If only the researchers had had some study participants follow the healthier, plant-based diet without the fast to tease out fasting’s effects. Oh, but they did! About a thousand individuals fasted for a week on the same juice and vegetable soup regimen and others followed a normocaloric (normal calorie) vegetarian diet.

    As you can see below and at 2:54 in my video, both groups experienced significant increases in both physical and mental quality of life, and, interestingly, there was no significant difference between the groups.

    In terms of their major health complaints—including rheumatoid arthritis; chronic pain syndromes, like osteoarthritis, fibromyalgia, and back pain; inflammatory and irritable bowel disease; chronic pulmonary diseases; and migraine and chronic tension-type headaches—the fasting group appeared to have an edge, but both groups did well, with about 80 percent reporting improvements in their condition and only about 4 percent reporting feeling worse, as you can see below and at 3:25 in my video. 

    Now, this was not a randomized study; people chose which treatment they wanted to follow. So, maybe, for example, those choosing fasting were sicker or something. Also, the improvements in quality of life and disease status were all subjective self-reporting, which is ripe for placebo effects. There was no do-nothing control group, and the response rates to the follow-up quality of life surveys were only about 60 to 70 percent, which also could have biased the results. But extended benefits are certainly possible, given they all tended to improve their diets, as you can see below and at 4:00 in my video.

    They ate more fruits and vegetables, and less meats and sweets, and therein may lie the secret. “Principally, the experience of fasting may support motivation for lifestyle change. Most fasters experience clarity of mind and feel a ‘letting go’ of past actions and experiences and thus may develop a more positive attitude toward the future.”

    As a consensus panel of fasting experts concluded, “Nutritional therapy (theory and practice) is a vital and integral component of fasting. After the fasting therapy and refeeding period, nutrition should follow the recommendations/concepts of a…plant-based whole-food diet…”

    If you missed the previous video, check out The Benefits of Fasting for Healing.

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    Michael Greger M.D. FACLM

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  • Is Our Life Expectancy Extended by Intermittent Fasting?  | NutritionFacts.org

    Is Our Life Expectancy Extended by Intermittent Fasting?  | NutritionFacts.org

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    Alternate-day modified fasting is put to the test for lifespan extension. 

    Is it true that alternate-day calorie restriction prolongs life? Doctors have anecdotally attributed improvements in a variety of disease states to alternate-day fasting, including asthma; seasonal allergies; autoimmune diseases, such as rheumatoid arthritis and osteoarthritis; infectious diseases, such as toenail fungus, periodontal disease, and viral upper respiratory tract infections; neurological conditions, such as Tourette’s syndrome and Meniere’s disease; atrial fibrillation; and menopause-related hot flashes. The actual effect on chronic disease, however, remains unclear, as I discuss in my video Does Intermittent Fasting Increase Human Life Expectancy?. 
     
    Alternate-day fasting has been put to the test for asthma in overweight adults, and researchers found that asthma-related symptoms and control significantly improved, as did the patients’ quality of life, including objective measurements of lung function and inflammation. As you can see in the graphs below and at 0:56 in my video, there were significant improvements in peak airflow, mood, and energy. Their weight also improved—about a 19-pound drop in eight weeks—so it’s hard to tease out the effects specific to the fasting beyond the benefits we might expect from weight loss by any means. 

    For the most remarkable study on alternate-day fasting, you have to go back more than a half-century. Though the 2017 cholesterol findings were the most concerning data I could find on alternate-day fasting, the most enticing was published in Spain in 1956. The title of the study translates as “The Hunger Diet on Alternate Days in the Nutrition of the Aged.” Inspired by the data being published on life extension with caloric restriction on lab rats, researchers split 120 residents of a nursing home in Madrid into two groups. Sixty residents continued to eat their regular diet, and the other half were put on an alternate-day modified fast. On the odd days of the month, they ate a regular 2,300-calorie diet; on the even days, they were given only a pound of fresh fruits and a liter of milk, estimated to add up to about 900 calories. This continued for three years. So, what happened? 
     
    As you can see below and at 2:16 in my video, throughout the study, 13 participants died in the control group, compared to only 6 in the intermittent fasting group, but those numbers were too small to be statistically significant. 

    What was highly significant, though, was the number of days spent hospitalized: Residents in the control group spent a total of 219 days in the infirmary, whereas the alternate-day fasting group only chalked up 123 days, as you can see below and at 2:38 in my video. 


    This is held up as solid evidence that alternate-day fasting may improve one’s healthspan and potentially even one’s lifespan, but a few caveats must be considered. It’s not clear how the residents were allocated to their respective groups. If, instead of being randomized, healthier individuals were inadvertently placed in the intermittent fasting group, that could skew the results in their favor. As well, it appears the director of the study was also in charge of medical decisions at the nursing home. In that role, he could have unconsciously been biased toward hospitalizing more folks in the control group. Given the progress that has been made in regulating human experimentation, it’s hard to imagine such a trial being run today, so we may never know if such impressive findings can be replicated. 

    Well, that was interesting! I had never even heard of that study until I started digging into the topic.  

    Check out my fasting series and popular videos on the subject here.  

    For more on longevity, see related videos below.



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    Michael Greger M.D. FACLM

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  • Experts call for urgent mental health support for people living with long term autoimmune diseases

    Experts call for urgent mental health support for people living with long term autoimmune diseases

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    Newswise — More than half of patients with auto-immune conditions experience mental health conditions such as depression or anxiety, yet the majority are rarely or never asked in clinic about mental health symptoms, according to new research from the University of Cambridge and King’s College London.

    In a study published today in Rheumatology, researchers found that over half of the patients had rarely or never reported their mental health symptoms to a clinician, and that the range of possible mental health and neurological symptoms is much wider than has been previously reported.

    The team surveyed neurological and psychiatric symptoms amongst 1,853 patients with systemic auto-immune rheumatic diseases (SARDs) such as lupus and rheumatoid arthritis. The researchers also surveyed 289 clinicians, mostly rheumatologists, psychiatrists and neurologists, and conducted 113 interviews with patients and clinicians. 

    The 30 symptoms that the team asked about included fatigue, hallucinations, anxiety and depression. Among the patients in the study, experience of most of these symptoms was very widespread. 

    55% of SARD patients were experiencing depression, 57% experiencing anxiety, 89% had experienced severe fatigue and 70% had experienced cognitive dysfunction, for example. The overall prevalence of symptoms was significantly higher than previously thought, and much higher than in a control group of healthy volunteers.

    The mental health symptoms described by patients contrasted strongly with clinician estimates. For example, three times as many lupus patients reported experiencing suicidal thoughts compared to the estimate by clinicians (47% versus 15%). Clinicians were often surprised and concerned by the frequency and wide range of symptoms that patients reported to the researchers. 

    Some clinicians were much more focused on joint symptoms over mental health symptoms as they held the opinion that SARDs do not commonly affect the brain.

    However, other clinicians felt that these symptoms were under-estimated because patients were rarely asked about them in clinic. One rheumatology nurse interviewed said: “Doctors don’t go looking for it [hallucinations], so if we don’t ask we don’t think it exists much.”

    The study found disagreements between clinicians specialising in different aspects of care, but very few hospitals had effective systems where rheumatologists, neurologists and psychiatrists worked together.

    Dr Tom Pollak from the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, said the study highlights the importance of all clinicians asking their patients about mental health: “We have known for some time that having a systemic autoimmune disease can negatively affect one’s mental health, but this study paints a startling picture of the breadth and impact of these symptoms. Everyone working in healthcare with these patients should routinely ask about mental wellbeing, and patients should be supported to speak up without fear of judgement. No patient should suffer in silence.” 

    The study showed that patients were often reticent to report to clinicians mental health problems they might be having, sometimes feeling that they might be stigmatised. Patients frequently said that even when they did share their mental health symptoms with clinicians, they were often not commented on or not documented accurately or at all. 

    One patient expressed how this felt: “Feel guilty and useless as well as depressed and very unwell. I don’t really feel supported, understood, listened to, hopeful at all. It is awful living like this…. All just feels hopeless.” 

    Dr Melanie Sloan from the Department of Public Health and Primary Care at the University of Cambridge said: “The low level of reporting we identified is a major concern as problems with mental health, fatigue and cognition can be life-changing, and sometimes life-threatening. It’s only by fully engaging patients in their healthcare and by asking them for their views that we will be able to determine the extent of these often hidden symptoms, and help patients get the understanding, support and treatment they need.”

    The research team suggests that though they found neurological and psychiatric symptoms to be under-elicited in clinic, under-identified in research and under-represented in clinical guidelines, they described almost all clinicians as highly motivated to improve care. Rapidly evolving knowledge – including the behavioural and cognitive impacts of chronic inflammation and a widening range of potential biomarkers – means that there is grounds for optimism. 

    Sarah Campbell, Chief Executive of the British Society for Rheumatology, commented: “This study highlights the urgent need for improvements in the access patients have to integrated mental health support. Given what the study finds on the prevalence of this issue and the deep impact neurological and psychiatric symptoms have on patients, it should be of grave concern to policymakers that only 8% of rheumatology departments in England and Wales have a psychologist embedded in their team. We fully support the study team’s conclusion that more inter-disciplinary and patient-clinician collaboration is needed to ensure equity in the care of patients’ mental and physical health.”

    The Rt Hon the Lord Blunkett said: “It’s both surprising and deeply concerning that almost half of lupus patients have experienced suicidal thoughts, and that clinicians greatly under-estimate the mental health burden of these chronic diseases. This highlights the importance of extra funding for the NHS and the holistic care that is urgently needed for these patients. I echo the British Society of Rheumatologists’ concerns about the poor current provision of mental health support. Now is the time for the Government to act to give them the support they desperately need.”

    The research was funded by The Lupus Trust and LUPUS UK 

    Reference

    Sloan, M et al. Prevalence and identification of neuropsychiatric symptoms in systemic autoimmune rheumatic diseases: an international mixed methods study. Rheumatology; 26 Jul 2023; DOI: 10.1093/rhe/kead369

    ENDS 

    Once the embargo has lifted, the study will be live at: https://academic.oup.com/rheumatology/article-lookup/doi/10.1093/rhe/kead369

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    University of Cambridge

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  • CHOP Researchers Show that IgA Fine Tunes the Body’s Interactions with Microbes

    CHOP Researchers Show that IgA Fine Tunes the Body’s Interactions with Microbes

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    Newswise — Philadelphia, May 26, 2023—IgA deficiency is the most common primary immune deficiency worldwide, but its presentation has puzzled physicians and researchers. Some with the disorder present with symptoms like recurrent infections, autoimmune disease, or allergies, whereas others have no symptoms at all and only become aware of their IgA-deficient status through an incidental finding on a blood test. This variability has raised the question among researchers: Why aren’t many of those with IgA deficiency sicker? 

    A new study by researchers at Children’s Hospital of Philadelphia (CHOP) has begun to answer that question, demonstrating that IgA acts as a “tuner” that regulates the number of microbes the body sees every day, restraining the systemic immune response to these commensal microbes and limiting the development of systemic immune dysregulation.

    “Right now, if we identify IgA deficiency in a patient through a blood test, we have no way of knowing whether the patient will become symptomatic if they aren’t already, and we don’t know whether or when they might go on to develop a more serious immune deficiency,” said Sarah E. Henrickson, MD, PhD, an assistant professor and attending physician in the Division of Allergy and Immunology at CHOP and co-senior author of the paper, which was published today in Science Immunology. “Our paper lays the groundwork for being able to answer these critically important questions by providing a lens into how IgA and the microbiome interact and how an imbalance in that interaction could lead to symptomatic disease.”

    IgA (short for Immunoglobulin A) is an antibody protein that is part of the immune system and plays a role in fighting disease. It is found mainly in the respiratory and digestive tracts, but it can also be found in blood, saliva, tears, and breastmilk. To be diagnosed with IgA deficiency, patients must be over 4 years of age and have no IgA as determined through a blood test, as well as normal serum levels of IgG and IgM, without other known causes of immune deficiency. 

    Some researchers have suggested that perhaps IgM provides a “backup” role in some patients with IgA deficiency, explaining why some patients are asymptomatic. However, how secretory IgA and IgM work together in the mucosal system and whether their roles were redundant or distinct remained unclear.

    To investigate this further, the researchers analyzed samples from 19 pediatric patients with IgA deficiency and 13 pediatric control patients, from 15 families, and they then complemented that analysis with studies of IgA deficient mice. They sought to answer two questions: how mucosal antibodies like IgA and IgM and system antibodies like IgG interact with mucosal microbes, and how IgA deficiency affects equilibrium of the immune system. 

    Analyzing both blood and fecal samples, the researchers measured antibody levels; identified the microbial targets of IgA, IgM, and IgG antibodies; and performed immune profiling to gauge the activation of the immune system. In doing so, they showed that although IgA, IgM and IgG target overlapping sets of microbes, the role of IgA is distinct from IgM in restraining commensal microbes in the gut, and IgM only modestly compensates for the absence of intestinal IgA.

    They also determined that 26% of patients who were IgA deficient via blood tests had normal levels of IgA in their feces. Intriguingly, the patients with normal fecal IgA were less likely to develop immune dysregulation and clinical disease, as demonstrated through immune analysis of cytokine levels, whereas those deficient in both blood and fecal IgA were more likely to have elevated inflammatory cytokines and exhibit clinical symptoms.

    To validate their findings, the researchers studied knockout mice who lacked IgA. Mirroring the findings in human patients, these mice exhibited elevated cytokines and immune dysregulation. The researchers also found live microbes in fat tissue of the knockout mice, which was not found in healthy control mice, providing further evidence for a role for IgA in modulating systemic microbial exposure.

    “Based on these results, we propose that IgA supports the intestinal barrier to keep the proper balance of commensal microbes interacting with the immune system, acting as a tuner to keep the immune system in check,” said co-senior author Michael Silverman, MD, PhD, an Assistant Professor and attending physician in the Division of Infectious Diseases at CHOP. “Without IgA protecting the gut, commensal bacteria can get through, increasing a patient’s systemic exposure to these microbes and creating an inflammatory environment. Future studies with larger patient populations should investigate IgA levels in other target tissues and determine if these findings can be used to predict disease course and outcomes.” 

    Conrey et al. “IgA deficiency destabilizes immune homeostasis towards intestinal microbiota and increases the risk of systemic immune dysregulation,” Science Immunology, May 26, 2023, DOI: 10.1126/sciimmunol.ade2335

    #

    About Children’s Hospital of Philadelphia: A non-profit, charitable organization, Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the 595-bed hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as an inpatient hospital with a dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children’s Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit https://www.chop.edu. 

     

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    Children’s Hospital of Philadelphia

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  • In 2050, over 800 million people globally estimated to be living with back pain

    In 2050, over 800 million people globally estimated to be living with back pain

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    EMBARGOED: 08:30 hrs Australian Eastern Standard Time (AEST) Tuesday 23 May 2023 / 23:30 hrs UK (UK) Monday 22nd May

     

    Study estimates there will be over 800 million cases of low back pain in 2050, a 36 percent increase from 2020. With an ageing population, researchers say we must ‘put the brakes’ on low back pain cases before the burden becomes too great for our healthcare system.  

    Analysis of over 30 years of the GBD data has shown the number of cases of low back pain is growing, with modelling suggesting by 2050, 843 million people will be affected by the condition largely due to population increases and ageing of populations.

    The continued lack of a consistent approach on back pain treatment, and limited treatment options have researchers concerned that this will lead to a healthcare crisis, as low back pain is the leading cause of disability in the world. 

    In Australia, there will be a nearly 50 percent increase in cases by 2050. The landscape of back pain cases is set to shift, with the biggest increases in back pain cases to be in Asia and Africa.  

    The findings are published in Lancet Rheumatology today. 

    “Our analysis paints a picture of growing low back pain cases globally, putting enormous pressure on our healthcare system. We need to establish a national, consistent approach to managing low back pain that is informed by research,” says lead author, Professor Manuela Ferreira from Sydney Musculoskeletal Health, an initiative of the University of Sydney, Sydney Local Health District and Northern Sydney Local Health District.

    “Currently, how we have been responding to back pain has been reactive. Australia is a global leader in back pain research; we can be proactive and lead by example on back pain prevention”, said Professor Ferreira who is based at Sydney’s Kolling Institute.

    The study reveals several milestones in back pain cases. Since 2017, the number of low back pain cases has ticked over to more than half a billion people. 

    In 2020, there were approximately 619 million cases of back pain.

    At least one third of the disability burden associated with backpain was attributable to occupational factors, smoking and being overweight.

    A widespread misconception is that low back pain mostly affects adults of working age. But researchers say this study has confirmed that low back pain is more common among older people. Low back pain cases were also higher among females compared to males.

    This is the most comprehensive and up-to-date available data that includes for the first time global projections and the contribution of GBD risk factors to low back pain. The work was made possible by the joint efforts of The University of Sydney, the Institute for Health Metrics and Evaluation (IHME) at the University of Washington’s School of Medicine (healthdata.org), IHME’s international collaborators, and the Global Alliance for Musculoskeletal Health (gmusc.com).

    “We also know that most available data come from high-income countries, making it sometimes hard to interpret these results for low to mid-income countries. We urgently need more population-based back pain and musculoskeletal data from countries of low to mid-income,” said senior author Professor Lyn March from Sydney Musculoskeletal Health and the Kolling Institute.

    The study analysed GBD data from 1990 to 2020 from over 204 countries and territories to map the landscape of back pain cases over time. The GBD is the most comprehensive picture of mortality and disability across countries, time, age, and sex. 

    It is also the first study to be used for modelling the future prevalence of back pain cases. 

    “Health systems need to respond to this enormous and rising burden of low back pain that is affecting people globally.  Much more needs to be done to prevent low back pain and ensure timely access to care, as there are effective ways of helping people in pain” said Prof Anthony Woolf, co-chair of the Global Alliance for Musculoskeletal Health which is calling for priority to be given to addressing the growing burden of musculoskeletal conditions.

    “Ministries of health cannot continue ignoring the high prevalence of musculoskeletal conditions including low back pain. These conditions have important social and economic consequences, especially considering the cost of care. Now is the time to learn about effective strategies to address the high burden and to act” said Dr Alarcos Cieza, Unit Head, World Health Organization, Headquarters, Geneva

     

    National guidelines will form basis of back pain prevention

    In 2018, experts (independent to this study) voiced their concerns in The Lancet and gave recommendations, especially regarding exercise and education, about the need for a change in global policy on the best way to prevent and manage low back pain to stop the rise of inappropriate treatments.

    However, since then, there has been little change. Common treatments recommended for low back pain have been found to have unknown effectiveness or to be ineffective – this includes some surgeries and opioids. 

    Professor Ferreira says there is a lack of consistency in how health professionals manage back pain cases and how the healthcare system needs to adapt. 

    “It may come as a surprise to some that current clinical guidelines for back pain treatment and management do not provide specific recommendations for older people.” 

    “Older people have more complex medical histories and are more likely to be prescribed strong medication, including opioids for back pain management, compared to younger adults. But this is not ideal and can have a negative impact on their function and quality of life, especially as these analgesics may interfere with their other existing medications. This is just one example of why we need to update clinical guidelines to support our health professionals.”

    Co-author Dr Katie de Luca, from CQUniversity, said if the right action is not taken, low back pain can become a precursor to chronic health conditions such as diabetes, cardiovascular disease and mental health conditions, invasive medical procedures, and significant disability.

    “Low back pain continues to be the greatest cause of disability burden worldwide. There are substantial socio-economic consequences of this condition, and the physical and personal impact directly threatens healthy ageing.”

    -ENDS-

    Declaration: The authors declare no conflicts of interest.

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    University of Sydney

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  • Too Much Insulin Can Be as Dangerous as Too Little

    Too Much Insulin Can Be as Dangerous as Too Little

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    Newswise — Just over a century has passed since the discovery of insulin, a time period during which the therapeutic powers of the hormone have broadened and refined. Insulin is an essential treatment for type 1 diabetes and often for type 2 diabetes, as well. Roughly 8.4 million Americans use insulin, according to the American Diabetes Association.

    One hundred years of research have greatly advanced medical and biochemical understanding of how insulin works and what happens when it is lacking, but the reverse, how potentially fatal insulin hyper-responsiveness is prevented, has remained a persistent mystery.

    In a new study, published in the April 20, 2023 online edition of Cell Metabolism, a team of scientists at the University of California San Diego School of Medicine, with colleagues elsewhere, describe a key player in the defense mechanism that safeguards us against excessive insulin in the body.

    “Although insulin is one of the most essential hormones, whose insufficiency can result in death, too much insulin can also be deadly,” said senior study author Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology at UC San Diego School of Medicine.

    “While our body finely tunes insulin production, patients who are treated with insulin or drugs that stimulate insulin secretion often experience hypoglycemia, a condition that if gone unrecognized and untreated can result in seizures, coma and even death, which collectively define a condition called insulin shock.”

    Hypoglycemia (low blood sugar) is a significant cause of death among persons with diabetes.

    In the new study, Karin, first author Li Gu, PhD, a postdoctoral scholar in Karin’s lab, and colleagues describe “the body’s natural defense or safety valve” that reduces the risk of insulin shock.

    That valve is a metabolic enzyme called fructose-1,6-bisphosphate phosphatase or FBP1, which acts to control gluconeogenesis, a process in which the liver synthesizes glucose (the primary source of energy used by cells and tissues) during sleep and secretes it to maintain steady supply of glucose in the bloodstream.

    Some antidiabetic drugs, such as metformin, inhibit gluconeogenesis but without apparent ill effect. Children born with a rare, genetic disorder in which they do not produce sufficient FBP1 can also remain healthy and live long lives.

    But in other cases, when the body is starved for glucose or carbohydrates, an FBP1 deficiency can result in severe hypoglycemia. Without a glucose infusion, convulsions, coma and possibly death can ensue.

    Compounding and confounding the problem, FPB1 deficiency combined with glucose starvation produces adverse effects unrelated to gluconeogenesis, such as an enlarged, fatty liver, mild liver damage and elevated blood lipids or fats.

    To better understand the roles of FBP1, researchers created a mouse model with liver specific FBP1 deficiency, accurately mimicking the human condition. Like FBP1-deficient children, the mice appeared normal and healthy until fasted, which quickly resulted in the severe hypoglycemia and the liver abnormalities and hyperlipidemia described above.

    Gu and her colleagues discovered that FBP1 had multiple roles. Beyond playing a part in the conversion of fructose to glucose, FBP1 had a second non-enzymatic but critical function: It inhibited the protein kinase AKT, which is the primary conduit of insulin activity.

    “Basically, FBP1 keeps AKT in check and guards against insulin hyper-responsiveness, hypoglycemic shock and acute fatty liver disease,” said first author Gu.

    Working with Yahui Zhu, a vising scientist from Chongqing University in China and second author of the study, Gu developed a peptide (a string of amino acids) derived from FBP1 that disrupted the association of FBP1 with AKT and another protein that inactivates AKT.

    “This peptide works like an insulin mimetic, activating AKT,” said Karin. “When injected into mice that have been rendered insulin resistant, a highly common pre-diabetic condition, due to prolonged consumption of high-fat diet, the peptide (nicknamed E7) can reverse insulin resistance and restore normal glycemic control.”

    Karin said the researchers would like to further develop E7 as a clinically useful alternative to insulin “because we have every reason to believe that it is unlikely to cause insulin shock.”

    Co-authors include: Kosuke Watari, Maiya Lee, Junlai Liu, Sofia Perez, Melinda Thai, Joshua E. Mayfield, Bichen Zhang, Karina Cunha e Rocha, Alexander C. Jones, Igor H. Wierzbicki, Xiao Liu, Alexandra C. Newton, Tatiana Kisseleva, Wei Ying, David J. Gonzalez and Alan R. Saltiel, all at UC San Diego; Fuming Li, University of Pennsylvania and Fudan University, China; Laura C. Kim and M. Celeste Simon, University of Pennsylvania; Jun Hee Lee, University of Michigan.

    Funding for this research came, in part, from the National Institutes of Health (grants R01DK120714, R01CA234128, R01DK133448, P01CA104838, R35CA197602, R01DK117551, R01DK125820, R01DK76906, P30DK063491, R21HD107516, R00DK115998, R01DK125560 AND R35GM122523), the UC San Diego Graduate Training Program in Cellular and Molecular Pharmacology (GM007752) and the National Science Foundation Graduate Research Fellowship (#DGE-1650112).

    # # #

    Disclosure: Michael Karin and Alan Saltiel are founders and stockholders in Elgia Pharmaceuticals. Karin has received research support from Merck and Janssen Pharmaceuticals.

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    University of California San Diego

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  • Antibiotic resistance is an increasing problem. Learn all about it in the Drug Resistance channel.

    Antibiotic resistance is an increasing problem. Learn all about it in the Drug Resistance channel.

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    Staphylococcus aureus, Clostridioides difficile, Candida auris, Drug-resistant Shigella. These bacteria not only have difficult names to pronounce, but they are also difficult to fight off.  These bacteria may infect humans and animals, and the infections they cause are harder to treat than those caused by non-resistant bacteria. Antimicrobial resistance is an urgent global public health threat. According to the World Health Organization, antibiotic resistance leads to higher medical costs, prolonged hospital stays, and increased mortality. It kills at least 1.27 million people worldwide and they are associated with nearly 5 million deaths in 2019, according to the CDC. In the U.S., more than 2.8 million antimicrobial-resistant infections occur each year. Careful prescribing of antibiotics will minimize the development of more antibiotic-resistant strains of bacteria. Staying informed is another way to fight these dangerous “superbugs.” Below are some of the latest news updates on the topic of Drug Resistance.

    Scientists make critical progress toward preventing C. diff infections (embargoed until 26-Mar-2023 5:00 PM EDT)

    Resistant bacteria are a global problem. Now researchers may have found the solution

    Potential Treatment Target for Drug-Resistant Epilepsy Identified

    Brazilian researchers investigate diversity of E. coli bacteria in hospitalized patients

    A Quick New Way to Screen Virus Proteins for Antibiotic Properties

    New Class of Drugs Could Prevent Resistant COVID-19 Variants

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  • A common metabolite may help treat autoimmune diseases

    A common metabolite may help treat autoimmune diseases

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    Newswise — Researchers have revealed the modulatory effect of the anti-inflammatory metabolite itaconate on T helper and T regulatory cells, which may lead to new therapeutic approaches to treating some autoimmune diseases.

    Autoimmune diseases occur when the immune system attacks its own body. There are more than eighty known types of autoimmune diseases. In many cases, autoimmune diseases can be treated by suppressing the immune system; however, a side effect of such treatment is that the patient has an increased risk of severe infectious diseases, which is a leading cause of death. Hence there is a need to establish novel therapies for autoimmune diseases to reduce the risk of infectious diseases. 

    A research team led by Professor Tatsuya Atsumi, Assistant Professor Michihito Kono and graduate student Kuniyuki Aso at Hokkaido University, along with Senior Lecturer Masatoshi Kanda at Sapporo Medical University, has studied the effect of the molecule itaconate on the immune system. Their findings, which have implications for treating autoimmune disorders, were published in the journal Nature Communications.

    “Multiple sclerosis (MS) and systemic lupus erythematosus are two of the many autoimmune diseases caused by a dysregulation of T cells,” Kono explained. “We were interested in two types of T cells: T helper 17 (Th17) and regulatory T (Treg) cells. These cells have the same origin but have opposite functions in autoimmune diseases, and cell metabolites modulate their action. The metabolite we focused on was itaconate (ITA), as it has been shown to have anti-inflammatory, antiviral, and antimicrobial effects.”

    The researchers showed that, in cell cultures, ITA inhibited the differentiation of Th17 cells which have the potential to elaborate autoimmune diseases, and promoted that of Treg cells, which can ameliorate them. Further, in mice models with experimental autoimmune encephalomyelitis, ITA reduced the disease symptoms. Further tests were conducted to confirm that this effect was due to its effect on T cells.

    Investigations into the mechanism of action of ITA revealed that it inhibits essential metabolic pathways, glycolysis, oxidative phosphorylation, and methionine metabolism in Th17 and Treg cells. “ITA inhibits these pathways by directly inhibiting the enzymes methionine adenosyltransferase and isocitrate dehydrogenase, resulting in change of S-adenosyl-L-methionine/S-adenosylhomocysteine ratio and 2-hydroxyglutarate levels,” Kono elaborated. “The altered cell metabolites also indirectly affect the chromatin accessibility of essential transcription factors and the synthesis of proteins required for the differentiation of Th17 and Treg cells.”

    “Our results explain the mechanisms that underlie the modulation of T cell differentiation,” he concluded. “This could eventually lead to simple therapeutic approaches which regulate T cell differentiation, thereby treating T cell-mediated autoimmune diseases.”

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    Hokkaido University

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  • Immune cells have a backup mechanism

    Immune cells have a backup mechanism

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    Newswise — The enzyme TBK1 is an important component of the innate immune system that plays a critical role in the defense against viruses. Upon mutation-induced loss of TBK1 function, patients show an increased susceptibility to viral infections. Strikingly, if TBK1 is not expressed at all, this clinical effect is not seen. The mechanism behind this supposed discrepancy has now been elucidated by researchers led by Prof. Martin Schlee from the University Hospital Bonn and the Cluster of Excellence ImmunoSensation2 at the University of Bonn. The study was published in the journal Frontiers in Immunology.

    In the human body, viral particles are recognized by so called pattern recognition receptors (PRRs) situated within the cell or on the cell surface. Upon activation, a signaling cascade is initialized which ultimately results in the production and release of signaling molecules such as interferons and cytokines. These messenger molecules alert neighboring immune cells and point out the viral infection, inducing an immune reaction.

    Part of this signaling cascade is the TANK Binding Kinase 1 (TBK1). If viral particles are detected by PRRs, TBK1 is activated. TBK1 in turn activates two transcription factors which travel into the nucleus where they induce the transcription of interferon and cytokine genes.

    Susceptibility to viral infections

    Point-mutations in the TBK1 gene may induce a loss of function of TBK1. In humans, this manifests itself in clinical susceptibility to viral infections. Strikingly, this effect is not to be observed if TBK1 is not expressed and entirely lacking in the cell. “Surprisingly, a complete absence of TBK1 expression in humans is not associated with a reduced antiviral response,” says Prof. Martin Schlee of the Institute of Clinical Chemistry and Clinical Pharmacology at the University Hospital Bonn. Until now, it was unclear why a complete loss of TBK1 expression is better tolerated in terms of immunocompetence than a mutation of TBK1 affecting the kinase function.

    The Bonn researchers have now been able to provide an explanation for these previously unexplained observations. “A second enzyme that is very similar to TBK1 plays an important role in this: the IkB kinase epsilon, or IKKepsilon for short,” explains Dr. Julia Wegner, first author of the study. Just like TBK1, IKKepsilon acts downstream of PRRs and controls the expression of interferons. The two proteins are also very similar in structure, with more than 60 percent sequence homology. A novel finding is that TBK1 has a direct effect on IKKepsilon. “In myeloid cells, we could show that TBK1 regulates the expression of the related kinase IKKepsilon,” adds Dr. Wegner.

    No half measures

    TBK1 reduces the stability of IKKepsilon. This process is independent of the protein’s enzymatic function. “Accordingly, TBK1 that is nonfunctional due to point mutation is still able to destabilize IKKepsilon,” explains Prof. Gunther Hartmann, director of the Institute of Clinical Chemistry and Clinical Pharmacology and spokesperson of the ImmunoSensation2 Cluster of Excellence. “This leads to a continuous degradation of the kinase IKKepsilon in human immune cells.”

    Therefore, loss of TBK1 expression leads to an increased abundance of IKKepsilon. This mechanism ensures that an antiviral immune response can occur despite the absence of TBK1. Loss of function of TBK1 induced by point mutations, on the other hand, does not prevent destabilization and degradation of IKKepsilon, so that ultimately both factors are not available for viral defense. Increased susceptibility to viral infections is the result.

    Weapons of a virus

    In a healthy organism, increased amounts of IKKepsilon can thus compensate for the loss of TBK1. This becomes particularly important when viruses specifically seek to eliminate the body’s own defenses. Herpes simplex virus 1 (HSV-1), human immunodeficiency virus (HIV) but also severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are able to specifically induce TBK1 degradation. Also, several bacterial species are capable of causing the degradation of TBK1. “Our data clearly show that human immune cells have an important backup mechanism,” explains Dr. Wegner. “They are able to maintain an effective antiviral response even when pathogen-induced degradation of TBK1 occurs. Furthermore, the mechanism also takes effect in the case of genetic loss of TBK1.”

    Publication: Wegner Julia, Hunkler Charlotte, Ciupka Katrin, Hartmann Gunther, Schlee Martin (2023); Increased IKKepsilon protein stability ensures efficient type I interferon responses in conditions of TBK1 deficiency; Frontiers in Immunology , Vol. 14; DOI: 10.3389/fimmu.2023.1073608

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  • Family’s participation key to advancing diabetes research

    Family’s participation key to advancing diabetes research

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    Newswise — Individuals with Type 1 diabetes have a smaller pancreas than people without diabetes. This is surprising because insulin-producing beta cells account for just a small fraction of the pancreas, so the loss of beta cells in Type 1 diabetes would not be expected to reduce pancreas size.

    Now, a study of one family from Alabama has led Vanderbilt University Medical Center researchers to discover that insulin deficiency, independent of the autoimmunity associated with Type 1 diabetes, is the principal factor leading to a markedly smaller pancreas.

    Four members of this family of eight have monogenic diabetes from a rare mutation in the insulin gene, leading to insulin deficiency without autoimmunity. Magnetic resonance imaging (MRI) of the pancreas showed a reduced size and altered shape in the individuals with diabetes. This was similar to what had previously been observed in individuals with Type 1 diabetes. These new findings are published in Diabetes Care, a journal of the American Diabetes Association.

    “This is a wonderful story about the power of a single family to inform us about the process of a disease that affects millions of people,” said Daniel Moore, MD, PhD, associate professor of Pediatrics in the Ian Burr Division of Pediatric Endocrinology and Diabetes. “There are not many families, especially not large families, who are known to have exactly this form of diabetes, who could come forward to help us answer this question. But they responded to the call, and they’ve provided a really clear answer to a fundamental biologic question.”

    About two decades ago, David Pursell and his wife, Ellen, agreed that he and three of their six children who were diagnosed with diabetes would participate in research with the hope more could be learned about the disease. It was as simple as giving a little blood.

    They were surprised years later when a researcher from the University of Chicago’s Kovler Diabetes Center called to tell them that advances in science had revealed that the four actually had monogenic diabetes due to a mutation in the insulin gene instead of Type 1 diabetes.

    Last year, the Pursells were contacted by VUMC researchers who were collaborating with Siri Greeley, MD, PhD, and colleagues at the Kovler Diabetes Center’s Monogenic Diabetes Registry. The Vanderbilt research team asked if the family could travel to Nashville to have precise measurements of their pancreas taken at the Medical Center.

    The VUMC research team, which includes Moore, Jordan Wright, MD, PhD, Jon Williams, PhD, Melissa Hilmes, MD, and Alvin C. Powers, MD, along with colleague Jack Virostko, PhD, at The University of Texas at Austin, had previously found the reduction in pancreas size was present at the time of Type 1 diabetes diagnosis. The Vanderbilt investigators had also organized an international team, the Multicenter Assessment of the Pancreas in Type 1 Diabetes (MAP-T1D), to develop a standardized MRI imaging protocol to assess pancreas volume and microarchitecture.

    “We know the pancreas is much smaller in individuals with Type 1 diabetes, but there haven’t been good models to understand exactly what’s going on,” said Wright, an instructor in the Division of Diabetes, Endocrinology and Metabolism and first author on the manuscript. “This is the first time we can actually demonstrate in humans that insulin is a major factor in determining pancreas size and the loss of it leads to a much smaller pancreas.”

    David and Ellen and their now adult children, Peggy Rice, Vaughan Spanjer, Chrissy Adolf, Ramsey Nuss, and twin sons Parker and Martin Pursell, each had their pancreas size measured using the standardized Vanderbilt MRI protocol. David, Chrissy, Parker and Martin have monogenic diabetes.

    “When we talked to the doctors at Kovler, they asked if we’d be interested in participating in some trials or research and we said, ‘Of course, anything we can do,’” said David Pursell. “When we learned our diabetes was not caused by an immune response due to our islet cells being attacked by antibodies, then we thought maybe we’ve got the chance of getting an islet cell transplant.

    “But also, we’re obviously all in this together. If, by virtue of our family volunteering for this research we can help anyone else, we felt like it would be worth it.”

    This research was performed with assistance from the Vanderbilt University Institute of Imaging Sciences (National Institutes of Health [NIH] project 1S10OD021771-01), the Vanderbilt Institute for Clinical and Translational Research (UL1-TR000445) and the Institute for Translational Medicine (UL1-TR000430) and with the support of the Leona M. and Harry B. Helmsley Charitable Trust, the Juvenile Diabetes Research Foundation, the Doris Duke Charitable Foundation, the NIH (DK104942, DK129979) and the Vanderbilt and Chicago Diabetes Research and Training Centers (DK20593, DK20595).

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  • Putting out “the fire in the brain”

    Putting out “the fire in the brain”

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    Newswise — In autoimmune encephalitis, a rare but serious and sometimes life-threatening inflammation of the central nervous system, the body’s own defences are directed against the central nervous system. This disease was first identified in 2007, and the most common type is Anti-NMDA receptor encephalitis. In this autoimmune disease, a protein that plays an important role in signal transmission in the brain is disrupted: the NMDA-type glutamate receptor, or NMDA receptor for short. Researchers from Braunschweig, Jena, Leipzig and Berlin have developed a new potential treatment for this disease.

    In anti-NMDA receptor encephalitis, antibodies interfere with signal transmission in the brain. The receptors which the neurotransmitters glutamate and glycine bind to are internalised by the cells through antibody binding. This causes reduced signal transmission to neurons in the central nervous system. Those affected experience a wide variety of symptoms from epileptic seizures and psychoses such as hallucinations to loss of consciousness and coma. Patients describe the disease symptoms to be like a “fire in the brain” that they can’t control. The interdisciplinary DFG research unit SYNABS, consisting of researchers from several locations, is dedicated to the study of this disease.

    “It is our goal to better understand the disease mechanisms and to develop new and target-specific therapeutic approaches using modern biotechnology,” said the group’s spokesperson, Professor Christian Geis from Jena University Hospital. With their translational research approach, the group has been able to discover a potential therapeutic agent. The molecule consists of a part of an NMDA receptor and a fragment of a human antibody. The pathogenic antibodies then bind to this fusion construct rather than to the NMDA receptors.

    “To investigate whether the newly developed molecule can neutralise the antibodies, we used biochemical and microscopic methods on cultured nerve cells from mice and humans,” said Toni Kirmann, a doctoral researcher who is part of the SYNABS consortium in the Faculty of Medicine at Leipzig University. “We plan to try to apply this therapeutic approach to other forms of autoimmune encephalitis. In the long term, we hope that basic neuroscience research will help improve treatment options in neurology and psychiatry,” said Professor Stefan Hallermann of the Carl Ludwig Institute of Physiology in the Faculty of Medicine at Leipzig University.

    In this project, the TU Braunschweig developed the fusion construct and analysed it biochemically. The partners at Jena University Hospital and the Faculty of Medicine at Leipzig University initiated the DFG research unit and have analysed neurons and conducted in vivo studies. The partners at Charité and Freie Universität in Berlin have identified the affected autoimmune antibodies in patients.

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    Universitat Leipzig

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  • ‘Natural killer’ immune cells can modify tissue inflammation: study

    ‘Natural killer’ immune cells can modify tissue inflammation: study

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    Newswise — Melbourne researchers have improved our understanding of how the immune system is regulated to prevent disease, identifying a previously unknown role of ‘natural killer’ (NK) immune cells. 

    The Monash University-led study identified a new group of immune cells, known as tissue-resident memory natural killer (NKRM) cells. NKRM cells limited immune responses in tissues and prevented autoimmunity, which is when the immune system makes a mistake and attacks the body’s own tissues or organs.

    While additional research is required, the discovery may ultimately be used to treat autoimmune diseases like Sjogren’s Syndrome and possibly chronic inflammatory conditions.

    Published in Immunity, the preclinical research is led by senior author Professor Mariapia Degli-Esposti  and first author Dr Iona Schuster from the Monash Biomedicine Discovery Institute (BDI), in close ongoing collaboration with the Lions Eye Institute.

    Originally, NK cells were thought to be short lived cells that circulate in the blood with the sole function of identifying and quickly killing virally infected or damaged cells.

    The team’s previous research established that NK cells’ role is far more complex, and the latest study demonstrates for the first time that a subset of NK cells, NKRM, are critical in regulating immune responses in tissues.

    “This is key to preserving tissue function and preventing autoimmunity from developing,” Dr Schuster said. “While long-lived tissue resident memory T cells (TRM) have been described, the primary known function of these cells is to protect the host against reinfection.

    “Our discovery of tissue-resident memory natural killer (NKRM) cells establishes that the function of some memory cells that live in tissues is to protect from excessive inflammation rather than protect against recurring infection.”

    Professor Degli-Esposti, BDI Head of Experimental and Viral Immunology, said the findings significantly improved our fundamental understanding of how the immune system is regulated to prevent disease. 

    “One of the main obstacles in cancer immunotherapy … is the development of immune related adverse events, which include the development or flare-up of autoimmune complications,” she said.
    “These events are due to ‘super’ or ‘uncontrolled’ activation of the immune system as a result of the brakes being removed by the therapeutic strategy.

    “Furthermore, many therapies cause collateral damage to tissues where tumours are localised. Thus, NKRM may be an adjunct or follow-up therapy to restore immune balance and bring back tissue health.”

    Read the full paper in Immunity: Infection induces tissue resident memory NK cells that safeguard tissue health. https://www.cell.com/immunity/fulltext/S1074-7613(23)00026-2

    Key findings

    1. Following infection with a common virus, cytomegalovirus, ‘natural killer’ (NK) cells were recruited from the circulation into inflamed tissues where they were retained and developed into a long-lived population of cells that researchers called tissue-resident memory natural killer (NKRM) cells.
    2.  Unlike NK cells, NKRM did not participate in virus control.
    3. In the absence of NKRM, infection led to tissue damage and the development of autoimmunity which presented as Sjogren’s Syndrome, one of the most common autoimmune diseases.
    Therefore, researchers identified a new population of cells that specifically localise to tissues to modulate immune responses to prevent immune pathology and autoimmunity.

    About the immune system

    Dysregulated immune or inflammatory processes contribute to many diseases. While the immune system protects against infection, a dysregulated immune response can lead to chronic inflammation, and in some instances cause tissue damage. Viral infections can trigger these processes, as the Covid pandemic has highlighted.

    About autoimmune diseases

    Autoimmune diseases arise when immune responses are misdirected and the immune system attacks host tissues and organs. Appropriate regulation of immune responses is therefore critical. As an example, Sjogren’s Syndrome is one of the most common autoimmune diseases and severely affects vision as patients are not able to produce tears. In most cases this leads to severe discomfort, but complications can lead to corneal damage and compromise vision. There is no cure for Sjogren’s Syndrome or its ocular complications.

    About the Monash Biomedicine Discovery Institute
    Committed to making the discoveries that will relieve the future burden of disease, the Monash Biomedicine Discovery Institute (BDI) at Monash University brings together more than 120 internationally-renowned research teams. Spanning seven discovery programs across Cancer, Cardiovascular Disease, Development and Stem Cells, Infection, Immunity, Metabolism, Diabetes and Obesity, and Neuroscience, Monash BDI is one of the largest biomedical research institutes in Australia. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.

    About the Lions Eye Institute
    At the Lions Eye Institute, we make a difference to people’s lives through excellent patient care and by pushing the frontiers of science to discover new treatments and cures for eye disease. As a not for profit organisation, the Lions Eye Institute spans the dual complementary pathways of research and clinical care. We bring together a globally recognised team of researchers and clinicians who continually build on each other’s discoveries, knowledge and expertise to deliver sight-saving treatment and care around the world. The quest for knowledge and its life-changing applications for patients is what drives our work.
    For more Lions Eye Institute media stories, visit our news site.

    For more Monash media stories, visit our news and events site. 

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    Monash University

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  • A New Assay Screening Method Shows Therapeutic Promise for Treating Auto-Immune Disease

    A New Assay Screening Method Shows Therapeutic Promise for Treating Auto-Immune Disease

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    Newswise — Oak Brook, IL (January 27, 2022) – The January 2023 issue of SLAS Discovery contains a collection of four full-length articles and one technical brief covering cancer research, high-throughput screening (HTS) assay development and other drug discovery exploration.

    This month’s featured article, “A high-throughput MALDI-TOF MS biochemical screen for small molecule inhibitors of the antigen aminopeptidase ERAP1,” by Müller, et al, presents a newly developed matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) drug discovery assay for the endoplasmic reticulum aminopeptidase 1 (ERAP1). The dysregulation of ERAP1 has been associated with various auto-immune and auto-inflammatory diseases, making ERAP1 a high-profile target in drug discovery.

    The research team behind this study utilized an existing ERAP1 RapidFire MS (RF MS) assay on which to base their MALDI-TOF assay, producing greater assay stability, reproducibility and robustness for the MALDI-TOF platform. When results were compared between the pre-established RF MS and the MALDI-TOF platforms, shorter sample cycle times, reduced reagent consumption and a lower tight-binding limit were all advantages of the MALDI-TOF platform.

    Read this original research article to learn how the MALDI-TOF platform may detect other difficult targets, along with more research articles in the January issue of SLAS Discovery.

    The January issue of SLAS Discovery includes these additional articles:

    Access to the January issue of SLAS Discovery is available at https://www.slas-technology.org/issue/S2472-6303(22)X0007-1

    *****

    SLAS Discovery reports how scientists develop and use novel technologies and/or approaches to provide and characterize chemical and biological tools to understand and treat human disease. The journal focuses on drug discovery sciences with a strong record of scientific rigor and impact, reporting on research that:

    • Enables and improves target validation
    • Evaluates current drug discovery technologies
    • Provides novel research tools
    • Incorporates research approaches that enhance depth of knowledge and drug discovery success

    SLAS (Society for Laboratory Automation and Screening) is an international professional society of academic, industry and government life sciences researchers and the developers and providers of laboratory automation technology. The SLAS mission is to bring together researchers in academia, industry and government to advance life sciences discovery and technology via education, knowledge exchange and global community building.

    SLAS Discovery: Advancing the Science of Drug Discovery, 2021 Impact Factor 3.341. Editor-in-Chief Robert M. Campbell, Ph.D., Redona Therapeutics, Watertown, MA (USA).

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