Israeli Scientists Develop Breakthrough RNA Gene Therapy to Halt ALS Progression

TEL AVIV (VINnews) — In a potential game-changer for one of medicine’s most devastating diseases, researchers at Tel Aviv University have pioneered an RNA-based gene therapy that halts and even reverses nerve degeneration in models of amyotrophic lateral sclerosis, or ALS, offering fresh hope to millions worldwide battling the incurable neurodegenerative condition.

The findings, published this week in the peer-reviewed journal Nature Neuroscience, mark what scientists are calling a world first: the identification of a previously unknown molecular trigger for ALS progression and a targeted therapy to neutralize it. Led by Prof. Eran Perlson of TAU’s Gray Faculty of Medical and Health Sciences and Sagol School of Neuroscience, the international team uncovered how a drop in microRNA-126 — a tiny RNA molecule shuttled from muscles to nerves — sparks the buildup of toxic TDP-43 protein clumps that ravage motor neurons, leading to the muscle paralysis and respiratory failure that define ALS.

In preclinical tests using genetically modified mice engineered to mimic ALS, the therapy restored microRNA-126 levels, not only stopping the “fire-like” degeneration of nerves but also promoting regeneration of damaged cells. “We wanted to get to the root of what causes ALS to enable effective drugs for this incurable disease,” Perlson told The Times of Israel. “Our findings provide a clear path toward a therapy that could bring hope to millions of patients and their families.”

ALS, also known as Lou Gehrig’s disease, strikes about 2 in every 100,000 people annually, with no known cure. It progressively destroys motor neurons, leaving patients unable to move, speak or breathe; most succumb within three to five years of diagnosis. Current treatments, like the drug Riluzole, offer modest extensions of life but fail to address the underlying pathology.

The study, spearheaded in Perlson’s lab by postdoctoral researchers Dr. Ariel Ionescu and Dr. Lior Ankol, built on collaborations with Dr. Amir Dori, head of the Neuromuscular Disease Unit at Sheba Medical Center, as well as experts from Israel’s Weizmann Institute of Science, Ben-Gurion University of the Negev, and institutions in France, Turkey and Italy. By engineering an RNA delivery system to replenish microRNA-126, the team disrupted the toxic protein aggregation at ALS’s early stages — a mechanism that could also inform therapies for related disorders like Alzheimer’s, where similar protein buildups occur.

“This is a critical step forward,” Dori said in a statement from Sheba. “For the first time, we’ve shown we can intervene at the molecular level to protect neurons before irreversible damage sets in.”

While human trials are years away, the breakthrough has electrified the global ALS community. The ALS Association hailed it as “a beacon of innovation from Israel,” noting that the country’s robust biotech ecosystem — bolstered by institutions like TAU — continues to punch above its weight in medical research.c8cb0a Perlson emphasized the therapy’s potential scalability: “Adding microRNA-126 via gene therapy could be delivered non-invasively, targeting affected muscles to safeguard nerves system-wide.”

As researchers refine the approach for clinical translation, the discovery highlights Israel’s enduring contributions to global health. For ALS patients and families.