Breakthrough in ALS: RNA Therapy Opens New Avenue for Treatment

A groundbreaking international study led by Prof. Eran Perlson — a member of Tel Aviv University’s Sagol Center for Regenerative Medicine (SCRM) — has uncovered a molecular mechanism that may finally pave the way for effective treatment of Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disease long considered incurable.

Illustration showing the gene therapy’s protective effect on motor neurons, preventing the “fire-like” degeneration characteristic of ALS.

The research, conducted in Perlson’s lab at the Gray Faculty of Medical & Health Sciences and the Sagol School of Neuroscience, reveals how a specific RNA molecule can prevent and even reverse nerve degeneration. When the team added microRNA-126 to human cell cultures and animal models of ALS, motor neurons stopped degenerating and even began to regenerate .

The research team (Left to right): Dr. Ariel Ionescu, Prof. Eran Perlson & Tal Pery Gradus

The work builds on Perlson’s earlier discovery that toxic aggregates of the protein TDP-43 accumulate at the neuromuscular junction — where nerves connect to muscles — in ALS. The new study explains why: in healthy muscle, cells produce microRNA-126 and send it to nerve endings to suppress unnecessary TDP-43 production. In ALS, this protective signal is reduced, allowing TDP-43 to accumulate, damage mitochondria, and ultimately destroy motor neurons .

Importantly, restoring microRNA-126 reversed this process. Increasing its levels in tissue from ALS patients and in ALS-model mice reduced toxic TDP-43 buildup, preserved neuromuscular junctions, and supported nerve regeneration. These results point toward a future gene-therapy strategy centered on microRNA-126 supplementation, offering real hope to millions of patients worldwide .

Published in Nature Neuroscience, the study involved collaborators from Sheba Medical Center, the Weizmann Institute of Science, Ben-Gurion University, and partners across Europe, underscoring the global effort behind this scientific breakthrough.

The research was also highlighted in a recent article by the Jerusalem Post.