In a recent development, researchers have demonstrated that a one-time gene therapy can significantly slow down the progression of Huntington’s disease, offering the clearest evidence yet that the disease’s course can be altered.
Huntington’s disease is a rare genetic neurodegenerative disorder that annually affects one in 7000 Canadians, characterized by the breakdown of nerve cells in the brain, and has been believed to be untreatable.
Huntington’s disease is caused by a mutation in the HTT gene that codes for a protein called huntingtin. Since it’s an autosomal condition, meaning it affects chromosomes that aren’t sex chromosomes, there’s a 50 per cent chance that a child of an affected parent will develop Huntington’s disease later in life. In Canada, symptoms for Huntington’s disease begin appearing between the ages of 35 and 55, and life expectancy after diagnosis is limited to 10 to 25 years.
However, a recent clinical trial conducted by uniQure, a biotechnology company, and University College London’s Huntington’s Disease Centre claims to slow the progression of Huntington’s disease by 75 per cent, according to the company’s press release on Sept. 24.
The trial involves insertion of the harmless viral vector, a modified version of a virus genetically engineered to safely deliver genetic material such as a therapeutic gene into cells, AMT-130, directly into brain tissue through minimally invasive neurosurgery.
This kind of one-time gene therapy is unparalleled by the current standard of care for those affected by Huntington’s disease. AMT-130 gene therapy that targets the HTT gene is disease-modifying, targeting the underlying cause of Huntington’s disease, whereas the current disease management options for Huntington’s are symptomatic, addressing only the symptoms of the condition, not its root cause.
Current care options treat the triad of Huntington’s disease symptoms–chorea, irregular, random movements, dementia, decline in memory and cognition; and psychiatric disorders–with oral medication such as tetrabenazine, which treats chorea, as well as antipsychotics.
In an interview with the Journal, Neurology Assistant Professor from the Department of Medicine at Queen’s, and Neurologist and Movement Disorder Specialist at Kingston Health Sciences Centre, Dr. Nicholas Cothros shared his thoughts about the trial and its results.
“The study authors [Tabrizi, S., et al.] revealed early signals in their data that are very encouraging.” Dr. Cothros adds that the early results in the study, though promising, are preliminary. He mentions that the claim of the 75 per cent disease progression reduction after 36 months of the therapy is a composite measure that comes from aggregated data and dependent variables.
Dr. Cothros warned against the potential risks of gene therapy. Since the therapy uses the viral vector AMT-130, it can trigger immune responses, which can result in inflammation of the brain tissue and edema, buildup of fluid in the brain, which can be fatal.
The surgery required to deliver the gene therapy carries its own set of risks. “This study involves intra-striatal injections, a stereotactic neurosurgical procedure to deliver therapy to a vulnerable part of the brain in Huntington’s disease. Unlike an orally administered therapy, this carries a separate set of risks related to neurosurgery,” Dr. Cothros noted.
If this form of gene therapy becomes the future standard care for Huntington’s disease, Dr. Cothros suggested that the Canadian healthcare system would need to bridge accessibility gaps in order to ensure equitable treatment delivery to its patients.
“Neurologists are concentrated in urban centers, particularly with teaching hospitals and academic affiliations.” Dr. Cothros also spoke to the infrastructure required to support Huntington’s disease care. “The standard of care already requires a multidisciplinary team: not just neurologists, but also psychiatrists, neuropsychiatrists, and allied healthcare professionals.”
While further studies are required to understand the full scope of the treatment and its long-term effects and how feasible it is as a standard of care across Canada, the preliminary results offer a beacon of hope for those affected by this debilitating condition.
As research progresses, the prospect of a cure for Huntington’s disease moves closer to reality.
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cure, disease, Huntington's disease, treatments
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