Minipig Study Tests Gene Therapy for Huntington’s Disease


Huntington’s disease is a progressive neurodegenerative disorder that results from a mutation in the huntingtin gene, HTT. Currently, there is no cure for the disease.  

As we learn more about the underlying pathophysiology of Huntington’s disease, researchers continue to focus on the development of treatments that target the specific cause, rather than simply alleviating the disease symptoms. Gene therapy is one example of such therapeutic, and research in this area continues to grow, both in academia and industry.

A new body of work published in Science Translational Medicine outlines the preclinical testing of a microRNA-based gene therapy for Huntington’s disease – AMT-130 – in minipigs.

In simplistic terms, the therapy aims to prevent the production of the toxic mutant version of the HTT protein that causes Huntington’s disease. The research data from minipigs showed that intracerebral delivery of the therapy into the striatum resulted in widespread distribution and reduced mutant HTT protein for up to 12 months post injection.

Technology Networks spoke with Astrid Vallès, associate director in translational biology at uniQure, and Melvin Evers, senior director of preclinical biology at uniQure to learn more about the preclinical study, the gene therapy landscape and the next steps in the development of AMT-130.  

Q: Why are current treatment options for Huntington’s disease limited, and why is a gene therapy approach favorable?

Huntington’s disease is an autosomal dominant neurodegenerative disorder, caused by mutations (increased polyglutamine tract) in the huntingtin – HTT – gene. Current treatment options are indeed limited and only symptomatic, but fortunately, many promising therapies are in development as there is increased knowledge of the disease mechanisms. One of the most promising approach is to lower the expression of (mutant) HTT. With gene therapy, we can specifically and effectively reduce the expression of the disease-causative gene. Next to being very long lasting (a single administration of gene therapy can be effective for years), the big advantage of gene therapy is that it has the potential to be disease modifying.

Q: What are some of the key considerations when developing and testing a gene therapy for a neurodegenerative disorder?

Key considerations are biodistribution, safety, efficacy and biomarkers. For biodistribution, it is important to establish the brain regions where the gene therapy needs to be effective. In the case of Huntington’s disease, the first affected areas are caudate and putamen (deep brain regions), while other brain areas (like cortical regions) are affected later in the disease. For this reason, targeting both deep brain regions and cortical regions is considered key for disease modification.

For safety, it important that the approach has no detrimental effects. Many preclinical studies are done to assess the potential toxicology of the gene…

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