NIH Grant Funds n-Lorem Treatments for Multiple Patients with Ultra-Rare form of ALS

Rare Daily Staff

The nonprofit antisense oligonucleotide developer n-Lorem said that it treated nine patients with an ultra-rare form of amyotrophic lateral sclerosis during the first year of a three-year, $15 million grant from the National Institutes of Health.

The Ultra-Rare Gene-based Therapy (URGenT) program of the National Institute of Neurological Diseases and Stroke, provides funding to three patient programs a year. One of the first Silence ALS programs initiated by n-Lorem and Columbia University focused on a rare form of familial ALS caused by mutations in the CHCHD10 gene, which makes a protein that helps maintain mitochondria’s stability, structure, and function.

ALS is a fatal neurological disorder caused by the degeneration of motor neurons in the brain and spinal cord. People with ALS rapidly lose muscle strength and eventually, their ability to move, swallow, and breathe. In at least 10 to 15 percent of ALS cases, the disease is caused by a mutation in one of a large and growing number of ALS-associated genes. Silence ALS targets those ultra-rare ALS patients who have a genetic mutation found in only 1 to 30 affected individuals worldwide.

The work has been conducted as part of Silence ALS, a collaborative initiative established by Columbia University and n-Lorem that has developed an infrastructure to enable ASO discovery and development for carriers of ultra-rare ALS gene mutations.

“The goal of Silence ALS is to design and develop individualized ASOs for patients with ultra-rare genetic forms of ALS for whom commercial access to this powerful technology is not available,” said Neil Shneider, director of the Eleanor and Lou Gehrig ALS Center at Columbia University Irving Medical Center and the principal investigator of the URGenT-funded Silence ALS program. “ALS is a rapidly progressive disorder, and we aim to treat patients as early in their disease course as possible, ideally before symptoms develop. We know that the earlier we can establish and begin a treatment, the better the outcome will be.”

Mutant CHCHD10 protein is thought to be toxic to neurons, leading to ALS and related disorders like frontotemporal dementia. As a therapeutic approach, n-Lorem developed an ASO, nL-CHCHD-001, to reduce total levels of CHCHD10.

To date, the U.S. Food and Drug Administration has approved more than 20 n-Lorem applications for clinical trials of experimental medicines to treat patients with ultra-rare mutations, including three for nL-CHCHD10.

Nine of eleven CHCHD10-ALS patients enrolled in Silence ALS have been treated with nL-CHCHD-001 – one at the Mayo Clinic, Florida, and eight at Columbia University since March of 2024. At least four additional patients are expected to be treated in mid-2025.

n-Lorem said while it is too early to evaluate how the ASO is impacting the disease, the treatment appears to be safe and well-tolerated.

Under the current URGenT grant, n-Lorem plans to file additional Silence ALS INDs in 2025 for ALS patients with ultra-rare mutations in CHCHD10 and other ALS genes including TARDBP, a major focus of the Silence ALS Initiative.

“The NIH URGenT grant infused Silence ALS with the funding to rapidly discover, develop and provide ASO therapies that could have a profound change on patient’s lives,” said Stanley Crooke, chairman, founder and CEO of n-Lorem. “That we have been able to dose nine patients in the first year of the funding is evidence of the importance of this grant and the benefit it can bring to patients who had little to no therapeutic options. There is a substantial need for treatment, as we estimate that there are hundreds to thousands of nano-rare patients with ALS who lack any treatment options.”

Photo: Stanley Crooke, chairman, founder and CEO of n-Lorem