Experimental drug shows promise of treatment for young patients with rare form of ALS

Hans India

23-05-2025

Treatment with an experimental drug has shown significant improvements in young patients with a rare form of Amyotrophic Lateral Sclerosis (ALS) -- a progressive neurodegenerative disorder, said a team of US researchers on Friday.
ALS, also known as Lou Gehrig's disease, is a rare disorder that affects nerve cells in the brain and spinal cord, leading to the loss of motor neurons causing difficulty with movement, balance, coordination, and potentially even breathing.
While experimental therapies have so far slowed down the disease or halted its progression, the new treatment using ulefnersen (previously known as jacifusen) -- showed that functional losses in young patients can be reversed.
"When testing new drugs for ALS, we do not expect to see clinical improvement," said neurologist and scientist Neil Shneider at Columbia University.
But, "what we've seen in one patient is really unprecedented functional recovery. It's surprising and deeply motivating for us, the ALS research community, but also the community of ALS patients," he added.
Data from 12 patients -- all treated with the novel therapy for a rare form of ALS caused by a genetic mutation in a gene called FUS -- were presented in a case series published by Shneider online in The Lancet.
Though these gene mutations are responsible for only 1-2 per cent of ALS cases, they cause some of the most aggressive forms of ALS that begin in adolescents and young adults.
In patients with these mutations, toxic FUS proteins accumulate in the motor neurons that control the patient's muscles, eventually killing the neurons.
Two of the patients in the published case series showed a remarkable response to the experimental therapy, ulefnersen developed by Shneider in collaboration with California-based Ionis Pharmaceuticals.
One young woman, who has received injections of the therapy since late 2020, recovered the ability to walk unaided and to breathe without the use of a ventilator, both previously lost to ALS. She has lived longer with this disease than any other known patient with this juvenile-onset form of FUS ALS.
The second patient, a man in his mid-30s, was asymptomatic when he began treatment, but tests of electrical activity in his muscles indicated that symptoms would likely emerge soon. In three years of continuous treatment with the experimental drug, the man has yet to develop any symptoms of FUS-ALS and the abnormal electrical activity in his muscles has improved.
Overall, after six months of treatment, patients in the series experienced up to an 83 per cent decrease in a protein called neurofilament light, a biomarker of nerve damage.
"These responses show that if we intervene early enough and go after the right target at the right time in the course of the disease, it's possible to not only slow disease progression but actually reverse some of the functional losses," Shneider said.
Though most of the other symptomatic patients in the series did not survive their aggressive disease, Shneider said "Several apparently benefited from the treatment. The progression of their disease slowed, and they lived a longer life as a consequence."
The case series also showed that the drug is safe and well tolerated, with no serious adverse events related to the drug.
Following the results from the first of these patients, a global clinical trial of the drug is now in progress.
"Now we are eagerly awaiting those results, which we hope will lead to the approval of ulefnersen," Shneider said.