New Experimental Therapy Shows Promise for Rare ALS Variant

An innovative treatment under investigation may provide significant benefits for patients suffering from a rare genetic form of Amyotrophic Lateral Sclerosis (ALS), according to research conducted by neurologists at Columbia University. The drug, known as ulefnersen, is designed to target a specific mutation in the FUS gene, responsible for only 1-2% of ALS cases but linked to severe forms of the disease that typically manifest in younger patients.

During a recent study, data from twelve participants who received ulefnersen revealed some unexpected positive outcomes. While standard expectations for ALS clinical trials often focus on merely slowing disease progression, a few patients exhibited substantial improvements in their physical abilities.

One notable success involved a young female patient who began treatment in late 2020. Remarkably, she regained the ability to walk independently and breathe without mechanical assistance--functions she had lost due to ALS. Her experience marks her as the longest-surviving individual diagnosed with this particular juvenile-onset variant of FUS ALS.

Another participant, a male in his mid-30s who started treatment while asymptomatic, has remained free of any ALS symptoms after three years of therapy. Additionally, assessments of his muscle electrical activity have shown improvement, suggesting the therapy's potential to halt disease onset.

Overall, the study indicated that participants experienced a notable reduction in levels of neurofilament light, a biomarker associated with nerve damage, with some patients reporting decreases of up to 83% after six months of treatment.

These findings have sparked optimism within the ALS research community, highlighting the potential for early intervention and targeted therapies to not only slow but possibly reverse functional losses in patients. Although many participants in this study faced aggressive disease progression, several others appeared to benefit from ulefnersen, demonstrating slower disease advancement and increased longevity.

Importantly, the treatment has been well tolerated, with no serious adverse effects reported from the participants. Following the encouraging results from the initial patient cohort, a global clinical trial has been initiated to further assess the efficacy and safety of ulefnersen.

The origins of ulefnersen date back six years when a neurologist sought to aid a specific patient, Jaci Hermstad, whose twin had succumbed to ALS. Inspired by previous research indicating that FUS mutations lead to the production of toxic proteins detrimental to motor neurons, the team collaborated with Ionis Pharmaceuticals to develop a treatment that could potentially mitigate these harmful effects.

This novel therapy employs antisense oligonucleotides, which are specialized short DNA fragments designed to inhibit the expression of the FUS gene, thereby reducing the production of both toxic and normal FUS proteins. The initial success in Jaci's case paved the way for expanded access programs, allowing over 25 patients globally to receive this promising treatment.

As the global clinical trial progresses, researchers remain hopeful that ulefnersen will be approved for broader use, providing a new avenue of hope for individuals battling this challenging form of ALS.