Neurologists at Indiana University School of Medicine are among the first clinicians in the nation to administer a groundbreaking gene-based therapy for patients living with a rare form of amyotrophic lateral sclerosis (ALS).
The Food and Drug Administration approved tofersen, also called Qalsody, under its accelerated approval pathway in April, making the drug the first gene-based therapy available for patients with ALS—commonly called Lou Gehrig’s disease—who have a mutation in the superoxide dismutase 1 (SOD1) gene.
ALS is a progressive degenerative condition that affects nerve cells in the brain and spinal cord. These cells—motor neurons—carry signals to a person’s voluntary muscles, such as in the arms and legs. ALS mainly impacts a person’s physical control of their muscles.
Adam Comer, MD, assistant professor of clinical neurology in the Department of Neurology at IU School of Medicine, administered the therapy to the first patient at IU Health in October 2023. The treatment is delivered through a spinal injection—like a lumbar puncture— into an area of the spine that surrounds the brain and spinal cord. This results in the medicine flowing directly into the central nervous system to have the best effect.
“The benefit is long-term,” Comer said. “So far it appears to slow down the disease progression.”
Patients receive three initial doses at two-week intervals followed by doses every month.
Of the more than 31,000 patients in the United States living with ALS, according to the Centers for Disease Control and Prevention, this mutation affects about 1-2% of patients. Comer said past medicines approved for ALS haven’t targeted specific gene variants of the disease.
“This is actually trying to fix the problem at the genetic level,” Comer said.
Cynthia Bodkin, MD, associate professor of clinical neurology, said she had already started the process to fast-track the drug for implementation at IU Health, so that once it received FDA approval patients could receive the therapy as soon as possible.
“We knew we would find patients who would benefit from a treatment like this and potentially change the course of their disease,” Bodkin said.
A patient of Bodkin’s received the therapy during the clinical trial phase at another institution. Once he started the trial and returned to Indianapolis, Bodkin was amazed at the lack of decline.
“When I saw him back and saw how well he was doing, I cried,” Bodkin said. “He historically should not have been still alive. To see that he was still here was very emotional.”
Comer said neurologists at IU treat ALS patients with multiple genetic forms of the neurodegenerative disease. For the past five years, a genetic counselor in the ALS clinic, located at the IU Health Neuroscience Center in downtown Indianapolis, tests nearly all ALS patients for genetic variants. Recently released national guidelines stated that genetic tests should be offered to all ALS patients, Comer added.
“We’ve been ahead of the game. We’ve been counseling our patients and doing genetic testing for patients with ALS for many years so people already know they have this genetic variant,” Comer said.
IU School of Medicine neurologists treat about 200 ALS patients at any given time. Recently, they created an ALS repository for clinical research, called NEURO-LinQ, that collects ALS patient blood samples, medication information and other clinical data to study, Bodkin said.
Gene therapies targeting neuromuscular disorders is relatively new for neurologists to have available in the clinic. Historically, there has not been treatment for neurological genetic disorders that could change the progression of the disease, Bodkin said.
Also in October, a kindergartner from northern Indiana was the first patient in the state to receive a new gene therapy that could stop the debilitating and deadly effects of Duchenne muscular dystrophy. The patient was given this therapy, also the first of its kind, at Riley Children’s Health under the direction of Laurence E. Walsh, MD, associate professor of clinical neurology. DMD is a serious genetic muscle disease that often results in patients—typically boys in preschool to school-age years—losing the ability to walk by the age of 10 to 12.
“It’s amazing that we’re giving gene therapy for patients with neuromuscular disorders that we haven’t had any treatment available for during our careers as neurologists,” Bodkin said.