ALS May Be Autoimmune Disease, Study Shows

Amyotrophic lateral sclerosis (ALS) appears to be an autoimmune disease, according to the results of a recent study published in Nature.

"This 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," Alessandro Sette, Dr.Biol.Sci., professor at the La Jolla Institute for Immunology, said in the news release. The study was co-led by Sette and David Sulzer, Ph.D., a professor at the Columbia University Irving Medical Center.

ALS, formerly known as Lou Gehrig’s disease, is a rare, progressive neurodegenerative disorder that causes motor neurons in the brain and spinal cord to die. This causes muscles to weaken and eventually atrophy, resulting in the loss of voluntary movements such as walking, talking, and eventually, breathing.

Reports suggest that less than 30,000 people in the United States are living with ALS. The average survival time after an ALS diagnosis is three years, but approximately 10% of patients live with the disease for more than 10 years. For example, physicist Stephen Hawking, Ph.D., lived for 55 years following his diagnosis.

While previous research has linked environmental and genetic factors with ALS disease variation, Sette and Sulzer’s research suggests that a patient’s immune system may play a broader role in patient survival rate.

"There is an autoimmune component to ALS, and this study gives us clues as to why the disease progresses so rapidly," Sulzer added, also in the news release. "This research also gives us a possible direction for disease treatment."

Sette, Sulzer and their team of researchers found that ALS patients produce high numbers of inflammatory immune cells called CD4+ T. These cells mistakenly target the C9orf72 protein found in healthy neurons, leading to cell damage. This “self-attack” of the immune system is a hallmark of autoimmune conditions.

When they analyzed the blood cells of 40 ALS patients and 28 patients without, they noticed there were two distinct groups within the ALS cohort—patients with longer survival times and patients with shorter survival times. Both had high levels of CD4+ T cells, but patients with longer survival times also had more anti-inflammatory CD4+ T cells, which can regulate disease.

For example, when the body releases inflammatory T cells to eliminate a viral infection, anti-inflammatory CD4+ T cells are released afterward to prevent the inflammatory T cells from damaging healthy cells. Current study results suggest that anti-inflammatory CD4+ T cells protect neurons and slow ALS disease progression.

C9orf72 protein levels are impacted by gene mutations, which are common in ALS. More than 25 gene mutations are associated with ALS, and 40% of familial ALS cases and 10% of sporadic cases are associated with a C9orf72 gene mutation.

Sette’s lab also recently published research demonstrating the connection between autoimmunity and Parkinson's disease.

“Neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease were classically not considered to have autoimmune features,” the co-authors write in the study. “However, multiple sclerosis (MS) is associated with high levels of brain infiltration of T cells suspected to react with epitopes derived from viral-related or myelin-related proteins.”

"Hopefully, now that we know the specific target for these immune cells, we can make more effective therapies for ALS," Tanner Michaelis, the study’s first author and La Jolla Institute research technician, concluded in the news release.