Researchers Discover Potential Treatment for FUS-ALS Through Antisense Oligonucleotide jacifusen

Researchers at Columbia University Irving Medical Center have made a breakthrough in the treatment of FUS-ALS, a debilitating neurodegenerative disease, using an antisense oligonucleotide called jacifusen. The study, published in The Lancet, involved an expanded access program where 12 participants received serial intrathecal injections of jacifusen over a period of 2.8-33.9 months. The results showed a significant reduction in the concentration of neurofilament light chain in cerebrospinal fluid, a biomarker of axonal injury and neurodegeneration, with up to 82.8% reduction after 6 months of treatment. While some participants experienced continued functional decline, two showed unprecedented objective functional recovery and another remained asymptomatic with documented improvement in electromyographic abnormalities.

Key Takeaways:

• The researchers used an antisense oligonucleotide called jacifusen to treat 12 participants with FUS-ALS in an expanded access program.
• The participants received serial intrathecal injections of jacifusen over a period of 2.8-33.9 months.
• The results showed a significant reduction in the concentration of neurofilament light chain in cerebrospinal fluid, a biomarker of axonal injury and neurodegeneration.
• Up to 82.8% reduction in NfL concentration was observed after 6 months of treatment.
• Two participants showed unprecedented objective functional recovery and another remained asymptomatic with documented improvement in electromyographic abnormalities.
• The study was conducted through a series of single-patient investigational new drug applications at five sites, four hospitals in the USA and one in Switzerland.
• The researchers assessed safety using the Common Terminology Criteria for Adverse Events version 4.0 and standard cerebrospinal fluid metrics.
• Biochemical analysis and immunohistochemical staining were performed on post-mortem CNS tissues to quantify FUS protein expression and assess the burden of FUS pathology.

Statistics:

• 12 participants were enrolled in the expanded access program.
• 50% of participants experienced transient elevations in cell counts or total protein concentration in cerebrospinal fluid.
• The most common adverse events were back pain (50%), headache (33%), nausea (25%), and post-lumbar puncture headache (25%).
• 2 participants deaths were recorded during the program, both thought to be unrelated to the investigational drug.
• Up to 82.8% reduction in NfL concentration was observed after 6 months of treatment.
• 58% of participants were female and 42% were male, with a median age of 26 years (range 16-45).

Sources:

• Antisense oligonucleotide jacifusen for FUS-ALS: an investigator-initiated, multicentre, open-label case series. Lancet, 2025;405(10494):2075-2086.
• Lancet can be contacted at: Elsevier Science Inc, Ste 800, 230 Park Ave, New York, NY 10169, USA.