Experimental drug may benefit some patients with rare form of ALS

So it was a big surprise when some of the patients treated with an experimental drug -- a therapy that emerged from Shneider's research efforts -- showed improvements.

"When testing new drugs for ALS, we do not expect to see clinical improvement," Shneider says. "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."

Remarkable success stories

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% to 2% 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 (previously known as jacifusen), developed by Shneider in collaboration with 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 83% 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 disease, it's possible to not only slow disease progression, but actually reverse some of the functional losses," Shneider says. "It's also a wonderful example of precision medicine and therapeutic development based on science and an understanding of the biology of disease."

Though most of the other symptomatic patients in the series did not survive their aggressive disease, Shneider says "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.

After seeing results from the first of these patients, Ionis Pharmaceuticals committed to sponsoring a global clinical trial of the drug, led by Shneider, which is now in progress.

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