Collaboration Funds Experimental Therapy for Rare FUS-ALS

Eight patients will receive jacifusen, an experimental therapy for amyotrophic lateral sclerosis (ALS) caused by FUS gene mutations, under a joint effort from the ALS Association, Project ALS, and Columbia University’s Eleanor and Lou Gehrig ALS Center.

The new clinical research program, which will be supported by a two-year, $900,000 commitment from the ALS Association and Project ALS, aims to be the first step in developing a comprehensive strategy to treat rare forms of ALS.

“We want to develop simple pathways to treatments for all forms of genetic ALS, including rare types,” Neil Thakur, PhD, the ALS Association’s executive vice president of mission strategy, said in a press release.

Mutations in the FUS gene are present in about 5% of familial ALS and about 1% of sporadic ALS cases, and may lead to some of the most aggressive forms of ALS, including a type that begins during adolescence and young adulthood.

FUS mutations can result in the production of an abnormal FUS protein that is prone to form toxic aggregates, which can build up over time and lead to nerve cell damage.

Jacifusen is an experimental antisense oligonucleotide (ASO), or antisense therapy, for people with FUS-associated ALS. It consists of a small molecule designed to target the FUS mRNA — an intermediate molecule generated from DNA that works as a template for protein production — preventing the production of the FUS protein.

By lowering FUS protein levels, jacifusen — which is administered directly into the spinal fluid — may be able to slow disease progression.

Initially designed at Ionis Pharmaceuticals, jacifusen is being developed at Columbia’s Gehrig ALS Center under the leadership of its director, Neil Shneider, MD, Phd.

Jacifusen is named for Jaci Hermstad, a 26-year-old Iowa woman who was diagnosed with FUS-associated ALS in February 2019. Hermstad, who became the first patient treated with the experimental therapy, lost her identical twin sister to the same form of ALS in 2011.

“While it emerged from a tragedy, jacifusen represents teamwork at its best,” said Valerie Estess, director of research for Project ALS. “Doctors, drug companies, regulators, the Hermstad family, and Project ALS came together with the same goal,” allowing Jaci to receive the first dose of jacifusen less than four months after her diagnosis, Estess said.

To date, three ALS patients with FUS mutations have been treated with jacifusen under the U.S. Food and Drug Administration‘s (FDA) compassionate use protocol, supervised by Shneider.

“I am grateful to the ALS Association and Project ALS for providing the funding and infrastructure that allows our center to expand access to jacifusen humanely, responsibly, and rapidly,” said Shneider.

“This project is part of a larger strategy to resolve the scientific and regulatory impediments to making genetic therapies accessible and affordable for those who need them,” Thakur said. “We have been discussing this strategy with NINDS [National Institute of Neurological Disorders and Stroke] and FDA, and we look forward to carrying this work forward.”

“If we can provide the FDA with sufficient experience to streamline the approval of a genetic therapy to rare genetic forms of ALS, we will reduce the financial disincentives that prevent private investment in these treatments,” Thakur said in a blog post. “We will open up brand new avenues of treatment for genetic ALS — avenues that would have remained closed without our collaboration with Project ALS and Dr. Shneider.”

The clinical program will receive $650,000 from the ALS Association, in partnership with its Greater New York chapter, and $250,000 from Project ALS. Ionis Pharmaceuticals will provide additional support for ongoing pre-clinical studies of jacifusen and FUS-associated ALS, led by Shneider.