FDA Grants Orphan Drug Status to UC San Diego-Developed Gene Therapy for ALS

The popular Ice Bucket Challenge, in which people douse themselves with cold water to raise funds for charity, has significantly boosted research funding for the ALS Association and other groups. Photo credit: ALS Association

The U.S. Food and Drug Administration has granted orphan drug status to an experimental gene therapy for amyotrophic lateral sclerosis (ALS) developed and patented by Brian P. Head, PhD, adjunct professor in the Department of Anesthesiology at UC San Diego School of Medicine and a research health scientist at the VA San Diego Healthcare System.

Orphan drug status is given to certain drugs that show promise in the treatment, prevention or diagnosis of orphan diseases or conditions that affect fewer than 200,000 people in the United States. Though ALS (also called Lou Gehrig’s Disease) is well known (it is the subject of the widely popular Ice Bucket Challenge), it is considered a rare disorder that affects fewer than 30,000 people in the U.S., with an estimated 5,000 new cases diagnosed each year.

Orphan drug status provides the drugmaker Eikonklastes, which has licensed the therapy, with certain financial benefits to pursue development of the drug ET-101, also known as SynCav1, including first-in-human clinical trials.

In 2022, Head and colleagues reported that injecting a mouse model of ALS with SynCav1 protected and preserved spinal cord motor neurons and extended the longevity of the animals. ALS characteristically results in progressive damage and destruction of nerve cells in the brain and spinal cord, resulting in loss of motor control. Mean survival time after an ALS diagnosis in humans is two to five years.

Study treatment involved injecting a harmless adeno-associated viral vector carrying copies of the Caveolin-1 gene into the model mice, which provided instructions for producing a protein with the same name critical to cell-to-cell communications. By increasing production of the caveolin-1 protein, the gene therapy is believed to be neuroprotective and compensate for ALS-related nerve cell loss.

Head has also investigated whether SynCav1 might offer therapeutic promise for people with Alzheimer’s disease. In 2021, he and colleagues published a study suggesting the gene therapy helped prevent learning and memory loss in a mouse model.

— Scott LaFee