Hope Emerges for Aggressive Amyotrophic Lateral Sclerosis (ALS)

A study published in The Lancet reports that a new experimental drug has shown encouraging results in treating a rare, inherited form of Amyotrophic lateral sclerosis( ALS). While experimental drugs in clinical trials are often aimed at slowing or halting disease progression, this study delivered an unexpected outcome — patients demonstrated remarkable functional recovery (1^✔ ✔Trusted Source
Experimental drug may benefit some patients with rare form of ALS

Go to source). Dr. Neil Shneider, lead scientist and neurologist at Columbia University, stated, “When testing new drugs for ALS, we do not expect to see clinical improvement. What we've seen in one patient is unprecedented functional recovery. It's surprising and deeply motivating for us, the ALS research community, but also the community of ALS patients.”

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive neurological disorder that affects motor neurons in the brain and spinal cord. These neurons control voluntary muscle actions. When damaged, ALS leads to muscle weakness, atrophy, and, in advanced stages, can impair functions like chewing and breathing.

Targeting a Rare and Aggressive Genetic Mutation

While most ALS cases are sporadic, around 10% are inherited. Of these, 1–2% are linked to mutations in the FUS (fused in sarcoma) gene. This subtype typically affects younger individuals and tends to progress aggressively (2^✔ ✔Trusted Source
Experimental Drug Shows Promise Of Treatment For Young Patients With Rare Form Of ALS

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The Lancet study involved 12 patients with FUS-ALS, who were treated with an experimental antisense oligonucleotide drug called Ulefnersen (formerly known as jacifusen). Two patients showed particularly striking responses.

One young female patient, treated since late 2020, regained her ability to walk and breathe unassisted — both critical functions typically lost in ALS.

Another young male patient began treatment while still asymptomatic, though tests showed early signs of motor neuron damage. After three years of continuous therapy with ulefnersen, he remains symptom-free, and his abnormal muscle activity has improved.

Functional Recovery and Early Intervention

The case series noted that within six months of treatment, there was an 83% decline in neurofilament light, a protein biomarker for nerve damage. This suggests that early intervention with Ulefnersen may not only slow disease progression but also potentially reverse functional loss.

Importantly, the drug was well tolerated, with no serious side effects reported among the trial participants.

Although many symptomatic patients with advanced ALS in the study did not survive due to the disease’s aggressive nature, Dr. Shneider noted that “several apparently benefited from the treatment. The progression of their disease slowed, and they lived a longer life as a consequence.”

From a Single Patient to Global Trials

Ulefnersen was initially developed by Dr. Shneider and Ionis Pharmaceuticals for a single patient, Jaci Hermstad from Iowa, whose identical twin had previously died from the same condition. What began as a one-off treatment has now evolved into a full-fledged clinical trial, offering new hope to others with this rare ALS variant.

The drug belongs to a promising class of treatments known as antisense oligonucleotides (ASOs). These molecules work by silencing the FUS gene, thereby reducing production of the toxic protein that damages motor neurons.

Ulefnersen received FDA approval for investigational use in 2019, and to date, 25 patients have received the treatment. Encouraged by the results of this case series, a global clinical trial is now underway.

“Now we are eagerly awaiting those results, which we hope will lead to the approval of ulefnersen,” said Dr. Shneider.

With the global clinical trial underway, the ALS community watches with cautious optimism. If the promising results hold, ulefnersen could become the first targeted treatment for this rare and aggressive form of ALS — potentially changing the future for young patients worldwide.

References:

1. Experimental drug may benefit some patients with rare form of ALS - (https://medicalxpress.com/news/2025-05-experimental-drug-benefit-patients-rare.html)
2. Experimental Drug Shows Promise Of Treatment For Young Patients With Rare Form Of ALS - (https://www.bizzbuzz.news/industry/healthcare/experimental-drug-shows-promise-of-treatment-for-young-patients-with-rare-form-of-als-1362760)

Source-Medindia