Gene Therapy Offers First Potential Disease-Modifying Treatment for Huntington’s Disease
Boston, MA – In a landmark achievement for neurological medicine, researchers have, for the first time, demonstrated a potential disease-modifying treatment for Huntington’s disease using gene therapy. Early results from a clinical trial indicate that uniQure’s experimental therapy considerably reduced levels of the faulty huntingtin protein in the brains of patients, offering a glimmer of hope for those living with the devastating genetic disorder.
Huntington’s disease is a progressive neurodegenerative condition typically manifesting between the ages of 35 and 55. Symptoms begin subtly – often with loss of coordination or forgetfulness - and escalate to involuntary movements, mood swings, and cognitive decline. The disease is caused by an excess of repeating DNA sequences in the huntingtin gene, leading to the production of a faulty protein that progressively damages the brain. currently, available treatments only manage symptoms, offering no way to halt or reverse the disease’s progression.
Previous attempts at treatment focused on antisense therapy, a gene-targeted approach aiming to reduce production of the defective huntingtin protein. While initially promising, a leading candidate failed in late-stage testing in 2021, with patients receiving the therapy actually appearing to fare worse than those given a placebo.
This setback spurred a shift towards gene therapy, a strategy designed for a one-time intervention to permanently silence or modify the problematic gene. uniQure’s approach utilizes a harmless virus to deliver instructions for creating a microRNA – a molecule recognized with a Nobel Prize in 2023 – directly into brain cells. This microRNA acts as a “muzzle,” blocking the molecular instructions (mRNA) that lead to the production of the faulty huntingtin protein.Once delivered,the viral instructions remain within the cells,enabling continued production of the therapeutic microRNA. Despite the promise of microRNA technology, it has yet to yield any approved medicines.
The treatment is administered through a complex surgical procedure involving precise placement of a cannula into the striatum – a brain region severely affected by Huntington’s disease - guided by magnetic resonance imaging. The therapy is then slowly infused into this area.
While these early findings represent a important step forward, further research and long-term monitoring are crucial to fully assess the therapy’s safety and efficacy. the results offer a renewed sense of optimism for the Huntington’s disease community, possibly paving the way for a future where the disease’s relentless progression can be halted or even reversed.
References:
1 https://www.nature.com/articles/s41587-020-0452-0
2 https://www.nature.com/articles/d41586-021-01177-7
