AMT-130 is an experimental gene therapy being developed by uniQure to treat patients with Huntington’s disease. The therapy has shown promising results in preclinical studies and has been granted orphan drug status by the U.S. Food and Drug Administration (FDA). Clinical trials are expected to begin in 2019.

How AMT-130 works

Huntington’s disease is caused by a mutation in the huntingtin (HTT) gene, which leads to the formation of an abnormal protein that misfolds and aggregates inside nerve cells. These aggregates cause nerve cell death, leading to loss of muscle coordination, behavioral abnormalities, and cognitive decline.

AMT-130 is a gene therapy designed to inhibit the production of the mutated form of the huntingtin protein. The therapy is composed of a small portion of synthetic genetic material called microRNA (miRNA), which, once inside the cell, binds to the messenger molecule carrying the genetic information necessary to make huntingtin protein, and marks it for degradation. The end result is the decreased production of the abnormal huntingtin protein.

AMT-130 is carried inside nerve cells via a modified, noninfectious virus called adeno-associated virus (AAV). Neurons have cell surface receptors capable of detecting and initiating the internalization of the virus into the cell, where the miRNA can be associated with the existing RNA for the huntingtin protein.

Studies with AMT-130

UniQure conducted preclinical proof-of-concept studies with AMT-130 in early 2016. The results of these studies demonstrated the potential of a one-time administration of AAV-delivered gene therapy to successfully silence the huntingtin gene.

In April 2017, uniQure published the results of another preclinical study demonstrating the widespread localization of AMT-130 in the brain and spinal cord following direct injection of the AAV vector in a primate.

The company also published data showing a widespread and effective virus distribution and extensive silencing of the human mutant huntingtin gene in minipigs (one of the largest animal models available for Huntington’s disease research).

In this latest study, AMT-130 was administered into the striatum and thalamus of the brains of minipigs and three months after treatment, widespread, dose-dependent distribution of AAV was observed throughout the brains of the pigs. The production of the huntingtin protein was decreased by more than 50 percent in all regions of the brain where AMT-130 was found.

Both the surgical procedure and AAV-miRNA treatment were well-tolerated by the animals with no adverse side effects.

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