Some ALS patients miraculously recover almost entirely. Doctors may have figured out why

Imagine losing the ability to move your arms, to walk, to speak, and eventually even to breathe on your own. This is the grim reality faced by patients with amyotrophic lateral sclerosis (ALS), often known as Lou Gehrig’s disease. Incredibly, a handful of patients wind up defying this devastating prognosis. Now, in a study published in the journal Neurology, researchers have uncovered a genetic clue that may explain why these rare individuals experience a remarkable reversal of their ALS symptoms.

ALS, often referred to as Lou Gehrig’s disease, is a neurological condition that progressively destroys motor neurons, the nerve cells responsible for controlling voluntary muscle movement. As these neurons die, patients gradually lose control of their bodies. The disease is usually unforgiving, with most patients remaining trapped in their own skin before succumbing within 2-5 years of diagnosis.

However, in an intriguing twist that has puzzled researchers for at least 60 years, a handful of patients somehow survive and regain their lost faculties. These individuals, dubbed “ALS Reversals,” initially display all the hallmarks of the disease but then experience a substantial and sustained improvement in their condition. It’s as if their bodies have found a way to hit the pause button on ALS, or even rewind the clock.

“With other neurological diseases, there are now effective treatments,” says Dr. Richard Bedlack, the Stewart, Hughes, and Wendt Professor in the Department of Neurology at Duke University School of Medicine, in a statement.”But we still don’t have great options for these patients, and we desperately need to find things. This work provides a starting point to explore how biological reversals of ALS occur and how we might be able to harness that effect therapeutically.”

To unravel this medical mystery, researchers at Duke Health and St. Jude’s Research Hospital conducted a genome-wide association study (GWAS), comparing the genetic makeup of 22 ALS Reversal patients with that of typical ALS patients. The results were striking.

The team identified a specific genetic variant that was significantly more common in the Reversal group. This variant, known as a single nucleotide polymorphism (SNP), is associated with reduced levels of a protein that blocks the IGF-1 signaling pathway. In simpler terms, it’s like turning down the volume on a gene that might be contributing to the progression of ALS.

What makes this finding particularly exciting is its potential implications for treatment. IGF-1, or insulin-like growth factor 1, has long been a target of interest in ALS research due to its role in protecting motor neurons. Previous studies have shown that ALS patients with rapid disease progression tend to have lower levels of IGF-1 protein. However, clinical trials aimed at increasing IGF-1 levels have yielded disappointing results.

This new discovery suggests a fresh approach to targeting the IGF-1 pathway.

“While it may not be effective to simply give people IGF-1, our study indicates we might have a way to go about it differently by reducing the levels of this inhibiting protein,” says Dr. Jesse Crayle, co-lead author of the study. “It is also possible that the prior studies with IGF-1 were just not adequately dosed or need to be dosed in a different way.”

If confirmed by further research, the finding could open up new avenues for ALS treatment. Scientists might be able to develop therapies that mimic the effect of this genetic variant, potentially slowing down or even reversing the course of the disease in a broader population of patients.

While this research represents a significant step forward, the road to developing new treatments based on these findings is likely to be long and challenging. Nevertheless, for the ALS community, any glimmer of hope is welcome news in the fight against this terrible disease.