Innovative Therapy Shows Promise for Rare ALS Treatment

Recent advancements in ALS research have highlighted the potential of an experimental drug that may offer hope for patients with a rare, aggressive form of the disease linked to specific genetic mutations. Dr. Neil Shneider, a neurologist at Columbia University Irving Medical Center, reports remarkable improvements in some patients treated with this novel therapy, ulefnersen, which was developed through his research efforts.

ALS, or amyotrophic lateral sclerosis, is a neurodegenerative disease that affects nerve cells responsible for muscle control. While most cases are sporadic, a small percentage, about 1-2%, are caused by mutations in the FUS gene. These mutations lead to the accumulation of toxic FUS proteins in motor neurons, rapidly progressing and often beginning in adolescence or young adulthood.

In a case series published in The Lancet, 12 patients with FUS-related ALS received ulefnersen. Two patients experienced extraordinary recoveries: a young woman who regained the ability to walk and breathe without assistance after years of decline, and a man in his mid-30s who remained symptom-free for three years despite being at high risk of developing symptoms. Overall, patients showed a significant reduction—up to 83%—in neurofilament light, a biomarker of nerve damage.

These results suggest that early intervention with targeted therapy can not only slow the progression but potentially reverse some functional losses in ALS patients. The treatment was well tolerated, with no serious side effects reported. Following these promising findings, a global clinical trial of ulefnersen is underway, with hopes of gaining regulatory approval.

The development of ulefnersen originated from efforts to help a single patient and evolved into a broader clinical approach. It employs antisense oligonucleotides—short DNA sequences designed to silence harmful gene expressions—targeting the FUS gene. This innovative approach aligns with precision medicine principles, aiming to tailor treatment based on individual genetic profiles.

Since its initial use in 2019 through expanded access programs, at least 25 patients worldwide have received ulefnersen. Researchers remain optimistic about its potential to alter the disease course and improve quality of life for those with this devastating condition.