Gene Therapy VY-HTT01 Can Protect Brain Cells from Damage Caused by HTT Faulty Gene, Results Show

One-time delivery of Voyager Therapeutics’ lead candidate gene therapy, VY-HTT01, effectively reduced the levels of the faulty gene responsible for Huntington’s disease in important brain areas of non-human large primates.

These positive preclinical results, together with other ongoing studies, are expected to support the submission of an investigational new drug (IND) application for VY-HTT01, and the launch of clinical studies in humans sometime in 2019, Dinah Sah, PhD, who is chief scientific officer of Voyager, said in a press release.

The latest data on Voyager’s investigational therapy for Huntington’s was discussed recently at the annual congress of the European Society of Gene and Cell Therapy (ESGCT) in Lausanne, Switzerland, in a scientific poster titled “Robust Huntingtin knockdown in cortex and putamen in large mammals using a novel dosing paradigm with VY-HTT01, an AAV gene therapy targeting Huntingtin for the treatment of Huntington’s disease.”

“We are very excited by the robust reductions of disease-causing gene expression that were achieved as part of our latest delivery optimization efforts,” Sah said.

This novel gene therapy candidate takes advantage of a harmless adeno-associated virus capsid (AAV1) to deliver a small molecule of RNA that can promote “silencing” of the faulty HTT gene, by preventing its translation into the abnormal huntingtin protein that causes the disease.

This virus-based strategy is often used safely in gene therapy applications. Still, each treatment needs to adapt the viral carrier to the particular situation to ensure the therapy is efficient.

In recent preclinical studies, researchers administrated VY-HTT01 to different brain areas in large non-primate animals to find the delivery protocol that could induce the best outcome in tissues affected by Huntington’s disease.

Using magnetic resonance imaging (MRI) as a visual guide, researchers administrated the therapy in the thalamus alone, or in both the thalamus and the putamen areas.

The results revealed that co-administration of VY-HTT01 into the putamen and thalamus could reduce HTT mRNA levels in deep brain tissues, on average by 68% in the caudate, 67% in the putamen, and 73% in the thalamus. It also reduced mRNA levels at the more superficial brain area, the cortex, by 32%.

mRNA is the intermediate molecule between any gene and its final product, the protein.

“Targeting the putamen and thalamus generated significant knockdown of the target HTT in the deep tissues of the brain as well as in the cortex, offering the potential to address the most prominent manifestations of the disease,” Sah said.

In general, VY-HTT01 was well-tolerated by the animals for up to five weeks upon administration, with no gene therapy-related changes in clinical presentation or adverse side effects.

The company also presented positive preclinical results of its VY-SOD102 gene therapy to treat amyotrophic lateral sclerosis (ALS).