A groundbreaking gene therapy has demonstrated the ability to significantly slow the progression of Huntington’s disease, potentially leading to the first effective treatment for this debilitating inherited brain disorder.
In a recent trial involving 29 participants in the early stages of Huntington’s-related decline, those who received a high dose of the novel therapy directly administered into their brains experienced a 75% reduction in disease progression over a three-year period compared to those in a control group.
The results were statistically significant across a range of clinical measurements, as shared by uniQure, the Amsterdam-based gene-therapy company behind the study. According to trial investigators, the participants receiving the treatment also showed a decrease in the levels of a toxic protein associated with neurodegeneration in their spinal fluid. Given these promising findings, uniQure executives announced plans to seek regulatory approval for the treatment next year.
Dr. Sandra Kostyk, a neurologist at the Ohio State University Wexner Medical Center and a trial participant, expressed optimism about the therapy’s potential impact. “This gene therapy is obviously a big step forward,” she stated. “The data look quite good.”
Dr. Kostyk emphasized that while slowing the disease’s progression could result in extended years of independence for individuals with Huntington’s, the treatment is not a cure. The small size of the trial necessitates caution in interpreting the results, which are still pending publication. “I think we need more time and more data,” Kostyk added.
Huntington’s disease typically manifests between ages 35 and 55, with symptoms escalating from subtle coordination loss to involuntary movements, erratic mood swings, and gradual cognitive decline. The condition is triggered by excessive DNA repeats in the huntingtin gene, leading to the production of a malfunctioning protein that gradually harms the brain. Currently, no therapies target this fundamental cause, leaving affected individuals with only symptomatic relief options.
Initial efforts to create treatments centered on antisense therapy, which utilized short strands of DNA or RNA to reduce the production of the defective huntingtin protein. While this strategy displayed promise in early clinical tests, optimism waned when a leading candidate failed in late-stage trials, with outcomes for recipients of the therapy being worse than those given a placebo.
This setback shifted focus toward gene therapy as an alternative approach, aimed at providing a single intervention that permanently silences or modifies the defective gene at its source.
uniQure’s gene therapy employs a harmless virus to deliver genetic instructions for creating a short RNA sequence known as microRNA into the affected brain cells. This microRNA is designed to ‘muzzle’ the faulty huntingtin gene by obstructing the molecular instructions encoded by its messenger RNA (mRNA), effectively halting the production of the defective protein. Notably, once inside the cells, the viral instructions remain, allowing the cells to continuously produce the therapeutic microRNA.
The discovery of microRNAs was honored with a Nobel Prize last year, although the technology has yet to translate into any approved medications.
The administration of this innovative therapy necessitates an intricate surgery, during which clinicians utilize magnetic resonance imaging to precisely insert a cannula through small openings in the skull. The treatment is then infused slowly into the striatum—a crucial area of the brain severely impacted by Huntington’s disease.
As researchers look ahead, the potential of this gene therapy to alter the trajectory of Huntington’s disease offers new hope for patients and their families.
image source from：nature
