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Future ALS therapies might boost protective CD4+ T cell responses and dial back harmful inflammation. Credit: Neuroscience News<\/p>\nSummary: A groundbreaking study has shown that ALS may actually be an autoimmune disease. Researchers discovered that CD4+ T cells attack neuron-associated proteins, driving rapid disease progression.<\/p>\n
Crucially, patients with more anti-inflammatory T cells survived significantly longer, revealing a protective immune response. These findings not only reframe ALS but also point to new treatment strategies targeting the immune system.<\/p>\n
Key Facts<\/p>\n
Autoimmune Link: ALS patients show CD4+ T cells attacking neuron proteins, a hallmark of autoimmunity.Two Patient Groups: Some patients had more protective T cells, correlating with longer survival.Therapeutic Potential: Modulating T cell balance could slow disease progression and inspire new treatments.<\/p>\n
Source: La Jolla Institute<\/p>\n
Around 5,000 Americans are diagnosed with amyotrophic lateral sclerosis (ALS) each year. About half of patients die within 14 to 18 months of being diagnosed, usually due to breathing failure. The exact cause of ALS has long been unknown.<\/p>\n
Now, scientists at La Jolla Institute for Immunology (LJI) and Columbia University Irving Medical Center have uncovered evidence that ALS may be an autoimmune disease. The researchers discovered that inflammatory immune cells, called CD4+ T cells, mistakenly target certain proteins that are part of the nervous system in people with ALS.<\/p>\n
Future ALS therapies might boost protective CD4+ T cell responses and dial back harmful inflammation. Credit: Neuroscience News<\/p>\n
\u201cThis is the first study to clearly demonstrate that in people with ALS, there is an autoimmune reaction that targets specific proteins associated with the disease,\u201d says LJI Professor\u00a0Alessandro Sette, Dr.Biol.Sci., who co-led the study with Professor\u00a0David Sulzer, Ph.D., of the Columbia University Irving Medical Center.<\/p>\n
The researchers found that people with ALS produce high numbers of CD4+ T cells that target a specific protein (called C9orf72), which is expressed in neurons. This kind of \u201cself-attack\u201d is the defining feature of autoimmune disease.<\/p>\n
\u201cThere is an autoimmune component to ALS, and this study gives us clues as to why the disease progresses so rapidly,\u201d says Sulzer. \u201cThis research also gives us a possible direction for disease treatment.\u201d<\/p>\n
The new study was published recently in\u00a0Nature.<\/p>\n
Scientists discover two patient groups\u2014with different survival times<\/p>\n
Although ALS usually progresses quickly, around ten percent of patients live with the disease for ten years or longer. Baseball player Lou Gehrig passed away just two years after his ALS diagnosis. In contrast, physicist Stephen Hawking, Ph.D., lived for 55 years following his diagnosis.<\/p>\n
Scientists aren\u2019t sure what accounts for this variation. Researchers have linked certain genetic and environmental factors to different ALS \u201csubtypes,\u201d but we don\u2019t have a broad explanation to account for different survival times in the majority of patients.<\/p>\n
The new study suggests the immune system plays a big role in patient survival times.\u00a0<\/p>\n
By examining T cell responses in ALS patients, the researchers were surprised to find two distinct patient groups. One group had shorter predicted survival times. Their inflammatory CD4+ T cells were quick to release inflammatory mediators when they recognized C9orf72 proteins.\u00a0<\/p>\n
The second patient group also had harmful inflammatory CD4+ T cells, but they also had higher numbers of different T cells, anti-inflammatory CD4+ T cells. This second group also had significantly longer projected survival times.<\/p>\n
Anti-inflammatory CD4+ T cells are important because they can regulate disease. When the immune system fights a viral infection, for example, it churns out inflammatory T cells to eliminate the infected cells. Once the immune system clears the virus, anti-inflammatory CD4+ T cells step in to prevent overzealous T cells from damaging healthy tissues.<\/p>\n
The scientists weren\u2019t expecting to observe this same process in ALS patients. The new research suggests that CD4+ T cells may reduce harmful autoimmune responses and slow the progression of ALS.<\/p>\n
\u201cThis protective T-cell response is strongest in people with a longer predicted survival time,\u201d says Emil Johansson, Ph.D., a Visiting Scientist in the Sette Lab.<\/p>\n
Next steps in ALS research<\/p>\n
Future ALS therapies might boost protective CD4+ T cell responses and dial back harmful inflammation, says LJI Research Technician Tanner Michaelis, who served as the study\u2019s first author.\u00a0<\/p>\n
\u201cHopefully, now that we know the specific target for these immune cells, we can make more effective therapies for ALS,\u201d says Michaelis.<\/p>\n
\u201cThis approach may be applicable for additional disorders such as Parkinson\u2019s, Huntington\u2019s, and Alzheimer\u2019s,\u201d adds Sette.<\/p>\n
In fact, the new research is just the latest breakthrough in the growing field of neuroimmunology.\u00a0Recent findings<\/a>\u00a0from the Sette Lab have also shown connections between autoimmunity and Parkinson\u2019s disease, another disease marked by the death of neurons.<\/p>\n \u201cThere are several neurodegenerative diseases where we now have clear evidence of immune cell involvement,\u201d says Sette. \u201cThis is turning out to be more of a rule of neurodegenerative diseases\u2014rather than an exception.\u201d<\/p>\n Additional authors of the study, \u201cAutoimmune response to C9orf72 protein in amyotrophic lateral sclerosis,\u201d include Cecilia S. Lindestam Arlehamn, April Frazier, James D. Berry, Merit Cudkowicz, Namita Goyal, Christina Fournier, Allison Snyder, Justin Y. Kwan, Jody Crook, Elizabeth J. Phillips, Simon A. Mallal, John Ravits, Karen S. Marder, and John Sidney.<\/p>\n Funding: The study was supported by LJI & Kyowa Kirin, Inc. (KKNA- Kyowa Kirin North America); the Swedish Research Council (grant2024-00175); the Freedom Together Foundation; and in part by the Intramural Research Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health.<\/p>\n Key Questions Answered:Q: What new discovery did researchers make about ALS?<\/p>\n A: Scientists found that ALS involves an autoimmune reaction, where CD4+ T cells mistakenly attack proteins in neurons, suggesting ALS is partly an autoimmune disease.<\/p>\n Q: How does the immune system affect survival times in ALS?<\/p>\n A: Patients fell into two groups\u2014one with highly inflammatory T cells and shorter survival, and another with more protective anti-inflammatory T cells and longer survival.<\/p>\n Q: What do these findings mean for future treatment for ALS?<\/p>\n A: Boosting protective T cell responses and reducing harmful ones may slow ALS progression, opening new therapeutic possibilities.<\/p>\n About this ALS and neurology research news<\/p>\n Author: Madeline McCurry-Schmidt<\/a>
Source: La Jolla Institute<\/a>
Contact: Madeline McCurry-Schmidt \u2013 La Jolla Institute
Image: The image is credited to Neuroscience News<\/p>\n