New Evidence Suggests ALS May Be an Autoimmune Disease Driven by Immune Cells Attacking Nervous System Proteins

Amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, affects approximately 5,000 Americans each year. Traditionally considered a disease with largely unknown causes, recent research has shed light on its potential autoimmune nature. Studies conducted by scientists at La Jolla Institute for Immunology (LJI) and Columbia University Irving Medical Center have revealed that immune system dysregulation plays a significant role in ALS progression.

The researchers discovered that inflammatory immune cells, specifically CD4+ T cells, mistakenly target key proteins within the nervous system—most notably a protein called C9orf72, which is expressed in neurons. This misguided attack resembles the autoimmune response seen in diseases like multiple sclerosis, where the body's immune system turns against its own tissues. The presence of these autoreactive T cells suggests that ALS might be driven by an autoimmune mechanism.

Professor Alessandro Sette from LJI explained, "This is the first clear evidence that in people with ALS, the immune system erroneously targets proteins associated with the disease." Meanwhile, Professor David Sulzer from Columbia added, "The autoimmune component we have identified helps explain the disease's rapid progression and opens new avenues for treatment development."

Remarkably, the study identified two distinct patient groups based on their immune response. One group exhibited quick inflammatory responses from CD4+ T cells recognizing C9orf72, correlating with shorter survival times. The second group, however, had higher levels of anti-inflammatory T cells, which appeared to regulate harmful immune responses and were associated with longer expected survival. This finding highlights the immune system's dual role in disease progression and potential for therapeutic intervention.

Looking ahead, scientists suggest that future ALS treatments could focus on enhancing protective T cell responses while suppressing harmful inflammation. Such strategies might slow disease progression and improve patient outcomes. This research not only advances our understanding of ALS but also aligns with a growing field of neuroimmunology, where immune system involvement in neurodegenerative diseases is increasingly recognized.

Recent discoveries from the Sette Lab have also linked autoimmunity to Parkinson's disease, indicating that immune dysregulation may be a common feature across neurodegenerative disorders. As Professor Sette notes, "Immune cell involvement in neurodegeneration is becoming the norm rather than the exception." The findings from this study were published in the journal Nature and could pave the way for innovative immune-targeted therapies for ALS and other neurological diseases.