Gene Therapy for Huntington’s Disease: Latest Advances
- Researchers have reported positive early results from a clinical trial testing a novel gene therapy for Huntington's disease.
- Huntington's disease is a progressive brain disorder caused by a defective gene.
- The gene therapy, known as WVE-128, utilizes a technology called GalNAC to deliver small interfering RNA (siRNA) to the brain.
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Gene Therapy Shows Promise in Early Huntington’s Disease Trial
What happened?
Researchers have reported positive early results from a clinical trial testing a novel gene therapy for Huntington’s disease. The therapy, developed by Wave Life Sciences, aims to reduce the production of the mutant huntingtin protein that causes the debilitating neurodegenerative disorder. Initial data indicates the treatment was well-tolerated and showed a dose-dependent reduction in mutant huntingtin protein levels in cerebrospinal fluid.
Understanding Huntington’s Disease
Huntington’s disease is a progressive brain disorder caused by a defective gene. This gene leads to the production of an abnormal protein that damages nerve cells in the brain. symptoms typically appear between ages 30 and 50 and include movement disorders, cognitive decline, and psychiatric problems. The disease is inherited, meaning a child of a parent with Huntington’s has a 50% chance of inheriting the gene and developing the disease.
Key Symptoms
- Movement Disorders: Involuntary jerking or writhing movements (chorea), rigidity, slow or abnormal eye movements, impaired gait and posture.
- Cognitive Impairment: Difficulty organizing, prioritizing, and focusing on tasks; lack of flexibility; difficulty learning new facts.
- Psychiatric disorders: Depression, anxiety, irritability, obsessive-compulsive behavior, and, in certain specific cases, psychosis.
How the Gene Therapy Works
The gene therapy, known as WVE-128, utilizes a technology called GalNAC to deliver small interfering RNA (siRNA) to the brain. This siRNA specifically targets and degrades the messenger RNA (mRNA) that carries the instructions for making the mutant huntingtin protein. By reducing the amount of mutant protein, the therapy aims to slow or halt the progression of the disease. Unlike some gene therapies, WVE-128 dose *not* alter the patient’s DNA; it temporarily silences the problematic gene.
Trial Results and Data
The Phase 1/2 trial involved 46 participants with early-stage Huntington’s disease. Researchers observed a statistically important and dose-dependent reduction in mutant huntingtin protein levels in the cerebrospinal fluid of participants who received the therapy. Importantly, the treatment was generally well-tolerated, with most adverse events being mild to moderate in severity. Though,one participant experienced a serious adverse event – transient elevated liver enzymes – which resolved with treatment.
| Dose Level (mg) | Mean Reduction in Mutant Huntingtin Protein (%) | Number of Participants |
|---|---|---|
| 20 | 28 | 10 |
| 40 | 36 | 10 |
| 60 | 56 | 10 |
| 80 | 63 | 16 |
Source: Wave Life Sciences, March 2024