A one-time gene therapy may significantly slow the progression of Huntington’s disease, raising hopes for the first treatment capable of altering the course of this rare, inherited brain disorder.
In a small trial of 29 participants in the early stages of Huntington’s-related decline, those who received a high dose of the therapy directly into their brains experienced a 75% reduction in disease progression over three years compared with a control group. The data, released this week by the Amsterdam-based gene-therapy company uniQure, also showed decreased levels of the toxic huntingtin protein in the spinal fluid of treated participants.
“This gene therapy is obviously a big step forward,” says Sandra Kostyk, a neurologist at Ohio State University Wexner Medical Center who participated in the trial. “The data look quite good.” While the therapy is not a cure, slowing disease progression could translate into many additional years of independence for patients, she notes.
Huntington’s disease is caused by excessive DNA repeats in the huntingtin gene, producing a defective protein that gradually damages the brain. Symptoms typically emerge between ages 35 and 55 and include involuntary movements, cognitive decline, and mood disturbances. Current treatments only manage symptoms rather than addressing the underlying genetic cause.
Unlike earlier antisense therapies, which aimed to reduce the defective protein but saw setbacks in late-stage trials, uniQure’s therapy delivers a short RNA sequence known as a microRNA directly into the striatum, a brain region severely affected by Huntington’s. The microRNA “muzzles” the faulty gene by blocking its molecular instructions, preventing cells from producing the toxic protein. The therapy is delivered via a complex surgical procedure using MRI-guided cannulas.
Most participants tolerated the treatment well, though some experienced headaches and other surgical complications. A rival program developed by Spark Therapeutics, now part of Roche, is pursuing a similar gene-therapy strategy. Both therapies are expected to cost over US$1 million per patient, highlighting concerns about accessibility and health-system burden.
Despite these challenges, researchers are optimistic. “This feels like it could be a turning point,” says Andrew Duker, a neurologist at the University of Cincinnati. Kyle Fink, a neuroscientist at the University of California, Davis, adds that the results are “the first step in really demonstrating that Huntington’s disease can be slowed down” and pave the way for next-generation treatments, including potential gene-editing approaches such as CRISPR.
As reported by Nature, uniQure’s findings represent a landmark in Huntington’s research, offering a glimpse of a future in which a previously untreatable genetic disease might be substantially slowed, if not eventually cured.
