Steps in Translating Genetic Discoveries Into Effective Treatments for ALS: Matthew B. Harms, MD

WATCH TIME: 5 minutes

"Much of what we’ve learned is translating faster than ever if it’s a genetically identified target… The prospect for translating to the clinic is going faster than ever."

Over the past decade, genetic research has revolutionized the understanding and treatment of amyotrophic lateral sclerosis (ALS). Advances in gene sequencing technologies have allowed scientists to identify numerous genetic mutations associated with ALS, such as SOD1, C9orf72, FUS, TARDBP, and, more recently, SBTLC1 and SBTLC2. These discoveries have provided valuable insights into the underlying mechanisms of the disease, including protein misfolding, RNA metabolism, disruptions, and neuroinflammation.

In 2023, the FDA approved tofersen (Qalsody; Biogen), an antisense oligonucleotide, as the first and only treatment for patients with SOD1-ALS, one of the most common familial forms of the disease. Despite these recent achievements, challenges remain, particularly in translating genetic discoveries into accessible treatments. To get greater insights on how the clinical community can continue to bridge the genetic research realm with clinical care, NeurologyLive® sat down with Matthew B. Harms, MD, an associate professor of neurology at Columbia University Irving Medical Center, a Muscular Dystrophy Association (MDA) Care Center.

Harms, an ALS expert, is expected to give a talk at the upcoming MDA Clinical & Scientific Conference, held March 16-19, in Dallas, Texas, on the leveraging genetics for ALS therapeutics. Before the meeting, he gave an overview of the progress of clinical trials, such as those targeting SBTLC1 and SOD1 mutations, and noted the approval of tofersen as a milestone for genetic-based ALS therapies. However, he emphasized that sustained funding is critical to advancing basic science, preclinical studies, and clinical trials. Harms also discussed the improved comfort among ALS clinicians in offering genetic testing, with most clinics now providing comprehensive testing and counseling to identify patients eligible for emerging treatments. While significant strides have been made, he stressed the need for continued support to overcome funding and infrastructure barriers.

Registration for the 2025 MDA Conference is now open! The meeting is set to be held at the Hilton Anatole, Dallas, Texas, from March 16 to 19, 2025. To register and for more information, head to www.mdaconference.org