uniQure Aims to Begin First Human Trial of Investigational Gene Therapy AMT-130 for Huntington’s in 2018

Patricia Inacio PhD avatar

by Patricia Inacio PhD |

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AMT-130 gene therapy

uniQure expects to advance the clinical development of its Huntington’s disease investigational gene therapy, called AMT-130, during 2018.

The company says it plans to file an investigational new drug application (IND) with the U.S. Food and Drug Administration (FDA) in the second half of 2018. The first human clinical trial with AMT-130 should begin soon after the FDA’s anticipated acceptance.

“We ended 2017 with significant momentum across all of our programs and the cash to fund operations into 2020. Now that we have established robust, commercial-scale manufacturing in our Lexington [Massachusetts] facility, we are highly focused on the near-term initiation of our pivotal study of AMT-061 in hemophilia B and Phase I/II trial of AMT-130 in Huntington’s disease,” Matthew Kapusta, CEO of uniQure, said in a press release.

AMT-130 is an experimental gene therapy that works by inhibiting the production of the mutated or altered form of the huntingtin protein. It does this by carrying a small molecule, called microRNA, that binds to the messenger molecule carrying instructions for the production of the huntingtin protein and sends it to degradation. As a result, AMT-130 lowers the levels of the defective huntingtin protein.

The therapy is carried by a special class of virus – called adeno-associated virus (AAV) – that is unable to cause an infection to its host, working just as a vehicle to deliver AMT-130 to nerve cells. The internalization of AMT-130 is mediated by the internalization of the virus. Once inside the cell, the miRNA is capable of binding to the messenger RNA molecule for huntingtin.

If the IND application is accepted, AMT-130 would become the first AAV-based gene therapy tested in humans, according to uniQure.

uniQure has previously shown that AMT-130 improves motor coordination and survival in mouse models of Huntington’s disease (HD). These results were followed by a report showing that the therapy was able to penetrate the brain and spinal cord following direct injection in a primate.

The therapy received FDA’s orphan drug designation in October 2017.

Additionally, the company is developing its gene therapy pipeline for other diseases: AMT-12 for congestive heart failure, and AMT-061 for hemophilia B.

“We also are intensifying efforts to further expand our gene therapy product pipeline. In addition to AMT-126, our BMS [Bristol-Myers Squibb]-partnered gene therapy candidate for congestive heart failure, we have a number of promising early-stage projects focused on liver-directed and CNS [central nervous system] disorders. We expect multiple new INDs to be filed over the next two years, further leveraging our industry-leading manufacturing and technology platform,” Kapusta stated.

Comments

Michael Berry avatar

Michael Berry

Hi,

This sounds very similar to the IONIS-HTTRx study. Am I getting this mixed up? Or is this a different drug using the same logic (stop the messenger by binding to the molecule for deletion?)

Alfredo avatar

Alfredo

What can they do for children

Bill Kaemmerer avatar

Bill Kaemmerer

Dr. Inacio,
The wording of your description of the action of AMT-130 implies that AMT-130 is allele-specific against mutant huntingtin. Please check this. I believe that the lead candidate selected by uniQure (miH12-451) is non-allele-specific. (See Miniarikova et al., Molecular Therapy—Nucleic Acids (2016) 5, e297.)
Nevertheless, the news that uniQure plans to advance to first-in-human trials of their therapy in 2018 is exciting.

Jim Spiegel avatar

Jim Spiegel

What is the process to choose who participates in these trials?

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