Breakthrough in Treating Huntington's Disease with Gene Therapy
A single application of gene therapy has shown remarkable progress in delaying the advancement of Huntington's disease. This development could potentially mark the beginning of the first-ever treatment that can change the trajectory of this inherited, uncommon brain disorder.
In a preliminary trial involving 29 individuals in the early stages of the disease, those who received a high dosage of the treatment directly in their brains experienced a 75% deceleration of the disease over three years. This result was compared to a control group who did not receive the treatment.
Gene Therapy Offering New Possibilities for Incurable Brain Diseases
The trial was significantly successful according to various clinical metrics. A drop in the levels of a harmful protein associated with neurodegeneration was also observed in the spinal fluid of the individuals who underwent the therapy. Encouraged by these findings, the executives of the gene-therapy company responsible for the trial are planning to apply for treatment approval next year.
"This gene therapy is clearly a significant breakthrough," states Sandra Kostyk, a neurologist involved in the trial. She further adds that slowing down the progression of the disease could mean several additional years of self-reliance for Huntington's patients, although it is not a complete cure. With such a small number of participants, the results need to be considered as preliminary. More time and data are required for a definitive conclusion.
Huntington's Disease: A Progressing Threat
Those diagnosed with Huntington's disease generally witness the symptoms gradually worsening, typically starting between the ages of 35 and 55. It often starts with minor loss of coordination or memory, then escalates to involuntary movements, severe mood swings, and a gradual deterioration of memory and cognition.
The disease is triggered by an excess of DNA repeats in a gene called huntingtin, resulting in the production of a defective protein that slowly damages the brain. Unfortunately, there are no current therapies that address this root cause, and those who inherit the mutation can only rely on medication that alleviates symptoms.
Shifting Approach from Antisense Therapy to Gene Therapy
Earlier attempts at a cure centered on antisense therapy, a gene-focused strategy that utilizes short DNA or RNA strands to reduce the production of the defective huntingtin protein. Despite showing promise in early clinical development, the optimism faded when a promising candidate failed in advanced testing. This failure prompted a shift in focus towards gene therapy, aiming for a one-time intervention that permanently silences or modifies the faulty gene at its source.
The Power of Molecular Silencing
The gene therapy in question employs a harmless virus to bring the template for creating a short RNA sequence, known as a microRNA, directly into the cells in the affected brain regions. This microRNA is designed to suppress the defective huntingtin gene, thereby preventing the cells from producing the faulty protein. This process is achieved by blocking the molecular instructions encoded by the gene.
Administering the treatment involves a complex surgical procedure where clinicians use magnetic resonance imaging to accurately position a cannula through small holes in the skull. The therapy is then slowly infused into the striatum, a part of the brain particularly affected by Huntington's disease.