Multi-year Grant from National Institutes of Health URGenT Network Funds Treatment of Patients with Ultra-Rare CHCHD10-ALS

n-Lorem, a nonprofit foundation, today announced that nine patients with an ultra-rare type of amyotrophic lateral sclerosis (ALS) have been treated during the first year of a multi-year grant from the National Institutes of Health (NIH). The work has been conducted as part of Silence ALS, an initiative that aligns Columbia University and n-Lorem on the joint mission to develop personalized experimental antisense oligonucleotide (ASO) medicines to treat ALS patients with ultra-rare, pathogenic gene mutations.

The grant, awarded in 2024 under the Ultra-rare Gene-based Therapy (URGenT) program of the National Institute of Neurological Diseases and Stroke, provides $15 million over three years to fund three patient programs a year. One of the first Silence ALS programs initiated by n-Lorem and Columbia University has focused on a rare form of familial ALS caused by mutations in the CHCHD10 gene, which makes a protein that helps maintain the stability, structure, and function of mitochondria. 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, n-Lorem has filed and received approval for more than 20 investigational new drug (IND) applications from the U.S. Food and Drug Administration for patients with nano-rare mutations, including three INDs for nL-CHCHD10. Beginning in March 2024, 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. At least four additional patients are expected to be treated in mid 2025. While it is too early to evaluate how the ASO is impacting the disease, the treatment appears to be been 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.

“Funding for Silence ALS and all of our programs is highly important for us to fulfill our mission and bring optimized ASO medicines to nano-rare patients in need,” said Stanley Crooke, M.D., Ph.D., Chairman, Founder and CEO of n-Lorem. “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. 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.”

“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. 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,” said Neil Shneider M.D. Ph.D., director of the Eleanor and Lou Gehrig ALS Center, the Claire Tow Associate Professor of Motor Neuron Disorders in the Department of Neurology at Columbia University Vagelos College of Physicians and Surgeons and the principal investigator of the URGenT-funded Silence ALS program. “Silence ALS builds on n-Lorem’s ASO technology and infrastructure, which is unparalleled in its efficiency and scale and designed for just such a challenge.”

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 10-15% 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 “nano-rare” ALS patients who have a genetic mutation found in only 1 to 30 affected individuals worldwide.

The support reported in this release is through a grant from the NIH Ultra-rare Gene-based Therapy (URGenT) program (NS134684-01). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

About Silence ALS

Silence ALS is 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. Silence ALS also focuses on the comprehensive clinical and scientific evaluation of pre-symptomatic ALS individuals, with the goal of identifying and eventually treating ALS patients in advance of symptom onset or very early in the course of disease. Through the use of n-Lorem’s ASO technology, personalized experimental ASO medicines can be designed to target the underlying genetic cause of disease.

About n-Lorem

n-Lorem Foundation is a non-profit organization established to apply the efficiency, versatility and specificity of antisense technology to charitably provide experimental antisense oligonucleotide (ASO) medicines to treat nano-rare patients diagnosed with diseases that are the result of a single genetic defect unique to only one or very few individuals. Nano-rare patients describe a very small group of patients (1-30 worldwide) who, because of their small numbers, have few if any treatment options. n-Lorem Foundation was created to provide hope to these nano-rare patients by developing individualized ASO medicines, which are short strands of modified DNA that can specifically target the transcripts of a defective gene to correct the abnormality. The advantage of experimental ASO medicines is that they can be developed rapidly, inexpensively and are highly specific. To date, n-Lorem received over 300 applications for treatment with more than 140 nano-rare patients approved. n-Lorem was founded by Stanley T. Crooke, M.D., Ph.D., former chairman and CEO of Ionis Pharmaceuticals, who founded Ionis Pharmaceuticals in 1989 and, through his vision and leadership, established the company as the leader in RNA-targeted therapeutics. Follow us on Twitter, Facebook, LinkedIn and YouTube.

To learn more about n-Lorem’s mission at www.nlorem.org, and please consider giving to n-Lorem to bring hope, possibility and treatment options to these patients and families in need.

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