A groundbreaking gene therapy has demonstrated the ability to significantly slow the progression of Huntington’s disease, potentially heralding the first effective treatment aimed at altering the course of this rare, inherited brain disorder. In a recent small-scale clinical trial involving 29 participants at early stages of Huntington’s-related decline, those receiving a high dose of the therapy directly into their brains exhibited a remarkable 75% reduction in disease progression over three years compared to a control group.
Data released this week by uniQure, a gene-therapy company based in Amsterdam, highlighted the statistically significant benefits of this innovative treatment across multiple clinical measures. Investigators also noted a decrease in the levels of a toxic protein associated with neurodegeneration in the spinal fluid of participants who received the therapy. Following these promising results, uniQure plans to pursue regulatory approval for the treatment next year.
According to Sandra Kostyk, a neurologist at the Ohio State University Wexner Medical Center in Columbus, and a participant in the trial, “This gene therapy is obviously a big step forward. The data look quite good.” Kostyk emphasizes that slowing the disease's progression could lead to several additional years of independence for individuals with Huntington’s, although she cautions that it is not a cure. With the trial involving a limited number of participants, she advises that the results should be considered preliminary until further data is available, stating, “I think we need more time and more data.”
Individuals diagnosed with Huntington’s disease typically experience a gradual worsening of symptoms over the years, with onset generally occurring between the ages of 35 and 55. Initial symptoms may include subtle coordination issues or memory lapses, which can evolve into profound involuntary movements, extreme mood swings, and a gradual decline in cognitive functions.
The disease is caused by excessive DNA repeats in a gene known as huntingtin, leading to the production of a defective protein that progressively damages brain cells. Currently, there are no therapies that tackle the underlying genetic issue, leaving those with the mutation reliant on medications that only alleviate symptoms.
Early attempts to create a treatment focused on antisense therapy, a gene-targeted strategy involving short strands of DNA or RNA designed to reduce the production of the faulty huntingtin protein. Initial clinical trials showed promise; however, excitement waned in 2021 after a leading candidate failed during late-stage testing, indicating that patients receiving the therapy fared worse than those on a placebo. This setback prompted researchers to pivot towards a different approach: gene therapy.
uniQure’s gene therapy utilizes a harmless virus to deliver instructions for producing a short RNA sequence, known as a microRNA, directly into the cells of the affected brain regions. This microRNA is engineered to "muzzle" the defective huntingtin gene, effectively preventing the production of the harmful protein by blocking the molecular signals encoded by the gene's mRNA.
Once administered, the viral instructions remain within the cells, continuously generating the therapeutic microRNA. The discovery of microRNAs was recognized with a Nobel Prize last year, although the technology has not yet resulted in any approved treatments for neurological conditions.
Delivering this innovative therapy necessitates a complex surgical procedure. Clinicians employ magnetic resonance imaging (MRI) to accurately place a cannula through small openings in the skull. The therapy is then infused gradually into the striatum, a brain region that is among the first adversely affected by Huntington’s disease.
In conclusion, the recent advancements in gene therapy for Huntington’s disease represent a significant leap forward in the quest for effective treatments. As research progresses, there is growing hope for individuals affected by this debilitating condition.
