The discovery by a team from La Jolla Institute for Immunology has implications for treatment of the fatal disease.

Scientists at La Jolla Institute for Immunology and Columbia University Irving Medical Center have found evidence that amyotrophic lateral sclerosis (ALS) may be an autoimmune disease.

The team further discovered that inflammatory immune cells called CD4+ T cells mistakenly target certain proteins that are part of the nervous system in people with ALS.

The findings, published recently in Nature, may lead to new therapies for ALS, which affects about 5,000 people in the US annually, is fatal and has no cure or known cause.

“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,” LJI professor Alessandro Sette, who co-led the study with Columbia University Irving Medical Center professor David Sulzer, PhD, said in a press release.

The researchers found that people with ALS produce high numbers of CD4+ T cells that target a specific protein (called C9orf72), a “self-attack” typical of autoimmune disease.

Identifying an autoimmune component to ALS means insight into why the disease progresses so rapidly, which may lead to novel treatments.

Although ALS is usually fatal within two to five years, about 10% of patients live with the disease for more than 10 years; the reason for this variation is unknown.

The new study suggests the immune system plays a big role in patient survival times. 

The researchers were surprised to find two distinct patient groups: one with shorter predicted survival times and inflammatory CD4+ T cells that were quick to release inflammatory mediators when they recognized C9orf72 proteins. 

The second patient group also had harmful inflammatory CD4+ T cells but additionally had higher numbers of anti-inflammatory CD4+ T cells and significantly longer projected survival times.

Anti-inflammatory CD4+ T cells work to regulate disease, preventing inflammatory T cells from damaging health tissue once a virus is cleared. 

The scientists were not expecting to observe this same process in ALS patients, positing that CD4+ T cells may reduce harmful autoimmune responses and slow the progression of ALS.

“This protective T-cell response is strongest in people with a longer predicted survival time,” said Emil Johansson, PhD, a visiting scientist in the Sette Lab.Future ALS therapies might boost protective CD4+ T cell responses to dial back harmful inflammation; this approach may also apply to disorders such as Parkinson’s, Huntington’s and Alzheimer’s.