Identified a New Potential Therapy for ALS Linked to C9orf72 Gene Mutations

An important international study coordinated by the National Institute on Aging (NIH) and published in Cell Genomics, which involved several Italian research centers—particularly in Milan—has identified a promising therapeutic approach for patients with Amyotrophic Lateral Sclerosis (ALS) caused by mutations in the C9orf72 gene, the most common genetic form of the disease.

The study identified acamprosate, a drug already approved for the treatment of alcohol dependence, as a potential therapy to slow disease progression in patients with C9orf72 gene mutations. Experiments conducted on motor neuron cells derived from patients showed that acamprosate indeed has a neuroprotective effect comparable to or greater than riluzole, the current standard of care for ALS.

Researchers from the “Centro Dino Ferrari” of the University of Milan and the Fondazione IRCCS Istituto Auxologico Italiano – including Dr. Silvia Peverelli, Dr. Cinzia Tiloca, Prof. Nicola Ticozzi, Dr. Federico Verde, Prof. Antonia Ratti, and Prof. Vincenzo Silani – as well as from the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico – including Prof. Daniela Galimberti, Dr. Maria Serpente, Dr. Chiara Fenoglio, Prof. Elio Scarpini, Prof. Giacomo P. Comi, Prof. Stefania Corti, and Dr. Roberto Del Bo – contributed to this important study, which analyzed genomic data from over 41,000 individuals affected by ALS. The Italian group is part of the SLAGEN Consortium, established years ago to promote genetic research on ALS. Co-senior author of the work is Dr. Isabella Fogh, who spent extended periods in the UK with support from Centro Dino Ferrari, which has always generously supported researchers.

The researchers also discovered that genetic factors influencing the risk of developing sporadic ALS can modify the age of onset in patients with C9orf72 mutations, providing new insights into the variable clinical expression of the disease.

“The originality of the approach lies in initially focusing the research on gene variants influencing the age of onset in patients with C9orf72 mutations,” comments Prof. Nicola Ticozzi, “and then using this strategy to identify therapeutically effective molecules.”

“This study represents an important advance in understanding the mechanisms underlying C9orf72-related ALS and in identifying new therapies,” comments Prof.ssa Stefania Corti. “The innovative approach based on genomic data analysis also allowed the identification of an already available drug that could be rapidly tested in clinical trials.”

“The completeness of the study lies in confirming efficacy using in vitro models,” explains Prof.ssa Antonia Ratti, “obtained from induced pluripotent stem cells (iPSCs) differentiated into human motor neurons, providing a biologically valuable model to test clinically relevant molecules.”

“These results open new prospects for developing personalized therapies for ALS patients,” adds **Prof. Giacomo P. Comi. “The possibility of using an already approved drug could significantly accelerate the development of new treatments.”

“The availability of a close-knit consortium like SLAGEN and the decade-long collaboration between the two Centro Dino Ferrari sites,” concludes Prof. Vincenzo Silani, “represents a guarantee for scientific progress in a poorly treatable disease like ALS and a reference point for the growth of future generations of researchers.”

For more information:
Pierangelo Garzia
Head of Press Office
Auxologico IRCCS
garzia@auxologico.it
Tel. 0261911.2896

Researcher contacts:
Prof. Nicola Ticozzi: nicola.ticozzi@unimi.it
Prof.ssa Stefania Corti: stefania.corti@unimi.it
Prof.ssa Antonia Ratti: antonia.ratti@unimi.it
Prof.ssa Daniela Galimberti: daniela.galimberti@unimi.it
Prof. Giacomo P. Comi: giacomo.comi@unimi.it
Prof. Vincenzo Silani: vincenzo.silani@unimi.it