AB-1001 is an investigational gene therapy originally developed by BrainVectis, which was acquired by AskBio in 2020. AB-1001 was previously called BV-101. This is Phase I/II dose-finding study to evaluate the safety, tolerability, and the ability to produce the desired result (i.e., efficacy) of a one-time intracerebral injection of AB-1001 (previously BV-101) within the striatum of adults with early manifest Huntington’s disease.
AB-1001 will be given through MRI-guided neurosurgical techniques directed to target tissues in the basal structures of the brain. This approach uses a modified and harmless virus to deliver to brain cells of the caudate and the putamen a copy of the gene encoding the CYP46A1 enzyme. This is a neuron-specific enzyme which helps regulate brain cholesterol synthesis and metabolism, and is deficient in people with HD. By increasing the levels of the enzyme, the therapy is expected to normalize cholesterol metabolism in the brain, which may help slow neurodegeneration.
In two mouse models, this therapy showed the ability to repair the essential cholesterol pathway (which is damaged in HD patients), reduce mutant Huntington protein aggregation, provide neuroprotection, and restore neuronal function. The main goal of the new trial is to assess the safety of AB-1001 in up to 18 people with early manifest Huntington’s disease and specifically to identify the highest dose that can be given without unacceptable safety issues.
The trial will be in 2 parts with approximately 12-18 participants. The first part aims to find the correct AB-1001 dose and will have two arms (i.e., two groups of people with HD – one receiving a low dose of AB-1001 and other receiving a high-dose of AB-1001). The second part is an expansion of the trial. The exact number of participants will depend on the safety of part 1. This trial is called an open-label, meaning there is no placebo group. The participants will be rigorously monitored for 52 weeks and there is a long follow-up phase of 4 years.