This experimental drug could help young people with a rare and aggressive form of ALS

Independent

22-05-2025

An experimental drug could help young people with a rare form of ALS, researchers at New York's Columbia University Irving Medical Center announced on Thursday.
Known as 'ulefnersen,' the therapy showed promise in treating patients with FUS-ALS, which is caused by a genetic mutation in a gene called FUS. The gene provides instructions for making a protein and plays a crucial role in cellular processes. While the mutations are only responsible for between one and two percent of ALS cases, they cause some of the most aggressive forms of ALS that begin in adolescents and young adults.
Fewer than 30,000 people in the U.S. are living with ALS, which is also known as amyotrophic lateral sclerosis or Lou Gehrig's disease, while 5,000 people are diagnosed each year. The nervous system disease affects nerve cells in the brain and spinal cord, leading to a loss of muscle control that gets progressively worse. The exact cause of the disease remains unknown, but a small number of cases are genetic. There is no cure and it is, eventually, fatal.
'When testing new drugs for ALS, we do not expect to see clinical improvement,' neurologist and scientist Neil Shneider said in a statement. '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.'
Shneider, who developed the drug in collaboration with the biotech company Ionis Pharmaceuticals, published his findings in the peer-reviewed journal The Lancet.
Starting as an effort to help a single patient, the case series was small, including just 12 patients who were treated with the drug.
Two of the patients showed a remarkable response to the drug. A young woman who had received injections of ulefnersen since late 2020 regained the ability to walk unaided and to breathe without the use of a ventilator, both previously lost to ALS. The medical center said she has lived longer with this disease than any other known patient with this juvenile-onset form of FUS ALS.
A man in his mid-thirties was asymptomatic when he began treatment, but tests of electrical activity in his muscles indicated that symptoms would likely emerge imminently. However, after three years of treatment, he has yet to develop FUS-ALS symptoms and the abnormal electrical activity in his muscles has improved.
Lastly, the researchers found patients experienced an up to 83 percent decrease in a protein called neurofilament light — a biomarker of nerve damage — following six months on the drug.
'These responses show that if we intervene early enough and go after the right target at the right time in the course of disease, it's possible to not only slow disease progression, but actually reverse some of the functional losses,' said Shneider. 'It's also a wonderful example of precision medicine and therapeutic development based on science and an understanding of the biology of disease.'
While most of the other symptomatic patients did not survive their disease, Shneider said that 'several apparently benefited from the treatment. The progression of their disease slowed, and they lived a longer life as a consequence.'
There were no serious adverse events related to the drug and a global clinical trial is now in progress. At least 25 patients have been treated with the drug around the world, including the dozen in Shneider's case studies. It was first tested six years ago in an Iowa patient named Jaci Hermstad. The drug was originally named for her.
'Now we are eagerly awaiting those results, which we hope will lead to the approval of ulefnersen,' Shneider said.