Groundbreaking gene therapy could treat a deadly seizure disorder

Groundbreaking gene therapy could treat a deadly seizure disorder

By Allison Parshall edited by Claire Cameron

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

Dravet syndrome is usually diagnosed in a child’s first or second year of life and results in 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 seizure medications and therapeutic diets to manage the seizures that characterize the condition. But these treatments are often ineffective. “It is very rare that (a patient becomes) seizure free,” says senior author Helen Cross of University College London. The results were published on Wednesday i New England Journal of Medicine.

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Instead of treating the symptoms, the new drug aims to treat the underlying cause of Dravet syndrome by targeting the gene that usually causes it—SCN1A. Researchers gave varying doses of zorevunersen to 81 patients aged two to 18 in the US and UK. The medicine significantly reduced the number of seizures patients experienced and improved their daily functioning and quality of life. During 20 months, the patients had between 59 per cent and 91 per cent fewer seizures than before they started the treatment. Most side effects were moderate or mild.

The studies were designed to test the safety and tolerability of the medication at varying doses. Another study, a phase 3 randomized control trial, is underway, and it will more rigorously test how well the drug treats Dravet syndrome’s core symptoms. But the data from the studies published 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, Chief Science Officer of the Dravet Syndrome Foundation. “This level of improvement is meaningful in so many aspects of daily life.”

The overwhelming majority of people with Dravet syndrome carry a mutation on the gene SCN1A, which makes an important protein that controls how brain cells fire. The mutation breaks down these proteins, and in turn disrupts the balance of electrical activity in the brain, which can cause seizures. The condition also typically causes developmental delays, intellectual disability, and problems with communication and movement.

Zorevunersen effectively prevents SCN1A mutation from breakdown of the important proteins. It’s a type of medicine called an antisense oligonucleotide – a short string of synthetic genetic information that modifies the instructions for protein building inside cells.

Existing treatments for Dravet syndrome do not treat the motor, behavioral and cognitive problems that the condition causes. But it could be the new medicine. The early results suggest that zorevunersen improved the patients’ communication, coping 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 impactful results are the improvements in intellectual function and quality of life in 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 NO 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 “can be life-changing,” she says.

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