Tel Aviv [Israel], November 14 (HBTV): A team of international scientists has reported a breakthrough that could lead to an effective treatment for amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease long regarded as incurable, according to Tel Aviv University.
The findings, published this week in the peer-reviewed journal Nature Neuroscience, identify a previously unknown molecular mechanism that drives ALS and demonstrate a potential RNA-based gene therapy capable of stopping nerve degeneration and regenerating damaged nerve cells.
ALS is a progressive disease in which motor neurons gradually deteriorate, causing muscle weakness, paralysis, and ultimately respiratory failure. While the exact cause remains unclear, a combination of genetic mutations, environmental factors, and cellular malfunctions is believed to contribute. Current treatments focus on slowing disease progression, managing symptoms, and improving quality of life through medication and various therapeutic interventions.
The study was led by Ariel Ionescu and Lior Ankol in the laboratory of Prof. Eran Perlson at Tel Aviv University’s Grey Faculty of Medical and Health Sciences and Sagol School of Neuroscience. It was conducted in collaboration with Amir Dori, senior neurologist and head of the Neuromuscular Disease Unit at Sheba Medical Centre, along with researchers from the Weizmann Institute of Science, Ben-Gurion University of the Negev, and institutions in France, Turkey, and Italy.
Perlson told The Press Service of Israel that the findings provide a new understanding of how ALS begins and progresses, adding that the results open the door to a potential treatment strategy involving the restoration of a lost RNA signal to protect motor neurons.
The research focused on toxic aggregates of the protein TDP-43, which accumulate at nerve endings where they connect to muscles. The team discovered that healthy muscle cells release microRNA-126, a small RNA molecule that travels to nerve endings and prevents excessive TDP-43 from forming toxic clusters. In ALS patients, however, muscle cells produce less microRNA-126, enabling TDP-43 buildup, mitochondrial damage, and eventual motor neuron death.
Perlson told TPS-IL that this mechanism reveals a previously unknown process regulating the connection between nerves and muscles. He said the neuromuscular junction is believed to be one of the earliest sites of deterioration in ALS, leading to paralysis and death.
The study showed that reducing microRNA-126 in healthy nerve cells caused ALS-like degeneration, while increasing microRNA-126 in tissues derived from ALS patients and in model mice reduced TDP-43 levels, halted neuron degeneration, and even supported nerve regeneration. Perlson said adding microRNA-126 ‘rescues neurons damaged by ALS and prevents degeneration of the neuromuscular junction’.
Researchers are now working to translate the discovery into human treatment. Perlson said the goal is to develop a safe and effective method to deliver miR-126 throughout the body, potentially through viral vectors such as AAV, which are already approved for clinical use in the United States. He noted that the challenges will include ensuring efficient delivery to the neuromuscular junction, maintaining safety, and scaling up production for human application.
He added that the findings may also have implications for treating other diseases involving nerve-muscle connection damage, including neuromuscular junction disorders, injuries, and additional neurodegenerative conditions.
The discovery could also help doctors diagnose ALS earlier and aid the development of drugs or biologics that boost microRNA-126 levels or replicate its effects. Understanding how muscle-to-nerve RNA signalling influences protein aggregation may also guide treatments for other conditions involving toxic protein accumulation, such as Alzheimer’s disease.
Perlson said the findings offer ‘a clear path toward developing a therapy that could bring hope to millions of patients and their families worldwide’.
(ANI/TPS)