Pioneering gene therapy may treat a deadly seizure disorder

Pioneering gene therapy could treat deadly seizure disorder

By Allison Parshall edited by Claire Cameron

A pioneering gene therapy could help treat a rare seizure disorder called Dravet syndrome, according to the results of new clinical trials. The drug, called zorevunersen, shows promise, particularly for people with the condition who do not respond to existing treatments such as anti-epileptic drugs.

Dravet syndrome is usually diagnosed during a child’s first or second year of life and causes frequent seizures and intellectual disability. It can often be fatal: about 15 to 20 percent of children with the syndrome die before reaching adulthood.

Doctors currently prescribe antiepileptic medications and treatment regimens to manage the seizures that characterize the condition. But these treatments are often ineffective. “It is very rare that [a patient becomes] without seizures,” says lead author Helen Cross of University College London. The findings were published Wednesday in the New England Journal of Medicine.

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Instead of treating symptoms, the new drug aims to treat the underlying cause of Dravet syndrome by targeting the gene that usually causes it:SCN1A. Researchers gave zorevunersen at different doses to 81 patients aged 2 to 18 years in the United States and the United Kingdom. The drug significantly reduced the number of seizures patients experienced and improved their daily functioning and quality of life. Over a 20-month period, patients had between 59 percent and 91 percent fewer seizures than before starting treatment. Most side effects were moderate or mild.

The studies were designed to test the safety and tolerability of the drug at different doses. Another study, a phase 3 randomized controlled trial, is underway and will more rigorously test the drug’s effectiveness in treating the core symptoms of Dravet syndrome. But data from studies released today suggest that zorevunersen treats the underlying cause of the disease.

“These results are incredibly promising and the levels of improvement are unprecedented in this disease state,” says Veronica Hood, scientific director of the Dravet Syndrome Foundation. “This level of improvement is significant in many aspects of daily life. »

The overwhelming majority of people with Dravet syndrome carry a gene mutation SCN1A, which is an important protein that governs the functioning of brain cells. The mutation degrades these proteins, in turn disrupting the balance of electrical activity in the brain, which can cause seizures. This condition also typically causes developmental delays, intellectual disability, and problems with communication and movement.

Zorevunersen effectively prevents SCN1A mutation to degrade these important proteins. It’s a type of drug called an antisense oligonucleotide, a short string of synthetic genetic information that changes the instructions for building proteins inside cells.

Existing treatments for Dravet syndrome do not address the motor, behavioral, and cognitive problems caused by the disease. But the new drug might do it. Initial results suggest that zorevunersen improved patients’ communication, coping skills and motor skills, as well as other markers of quality of life. Videos accompanying the study showed apparent improvements in patients, including children, who took the drug.

“For me, the most striking results are the improvement in intellectual function and quality of life of these children. I cried when I first saw these videos,” says Lori Isom of the University of Michigan, who helped develop the drug but was not involved in the drug’s development. NEJM studies.

The drug “has the potential to completely change the long-term outcome of this disease,” says Ingrid Scheffer, a pediatric neurologist at the University of Melbourne who treats and studies Dravet syndrome and was also not involved in the new work. It “could change my life,” she said.

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