AMT-130 is an experimental gene therapy being developed by uniQure to treat patients with Huntington’s disease. The drug is still undergoing preclinical studies, but the company is hoping to file an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA) for AMT-130 in 2018.

How AMT-130 works

Huntington’s disease is caused by a mutation in the huntingtin gene leading to the formation of a protein that misfolds and aggregates inside nerve cells, causing their death and leading to the loss of muscle coordination, behavioral abnormalities, and cognitive decline. This eventually leads to physical and mental deterioration of the patient.

The goal of AMT-130 is to inhibit the production of the mutated or altered form of the huntingtin protein. The investigational drug 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 decreased production of the altered huntingtin protein.

AMT-130 is carried inside nerve cells via a 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 presented data showing a widespread and effective virus distribution and extensive silencing of the human mutant huntingtin gene in mini pigs (one of the largest Huntington’s animal models available).

In this latest study, AMT-130 was administered into the striatum and thalamus of the brains of mini pigs 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 events.

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