Novel Gene Therapy Uses Brain Surgery to Achieve Results For Huntington’s Disease Patients, Part Two

As discussed in Part I of this article, a recent HDBUZZ publication featured a news item stating that due to several severe adverse events occurring during the initial AMT-130 trial (NCT04120493) for Huntington’s disease, the trial is on hold. Researchers will be analyzing data and circumstances surrounding these events before continuing the studies.

About The AMT-130 Trial for Huntington’s Disease (NCT04120493)

AMT-130 is administered by way of brain surgery. Due to the inherent risks, the researchers commenced the trial with the utmost care. During the first two surgery patients were watched closely to prevent negative effects. Only after ensuring that all participants were in the best possible condition post-surgery, did the trial continue.

uniQure’s clinical trial for Huntington’s disease uses AMT-130 gene therapy administered one time only through a neurosurgical procedure.

Primary Goal: Safety and Tolerability

In order to achieve the intended goals of safety and tolerability, researchers tested both high and low doses of AMT-130. A total of thirty-six people enrolled in the study. Ten people in a control group were to receive imitation surgery consisting of a simulated surgical procedure limited to skin incisions and no burr holes in the skull. Twenty-six people were assigned to the treatment group.

The treatment group was compartmentalized even further with twelve people assigned to a low dose and fourteen to a high dose. Thus far twelve participants in the high dose group have had surgery.

uniQure announced the three adverse events in the AMT-130 study this year in early August. According to an independent safety review committee, three participants out of fourteen in the high-dose group developed severe side effects. Two participants in Europe who had surgery were reported to have swelling. A third participant in the U.S. complained of severe headaches and other symptoms that appeared to be related to the treatment.

Alternate Studies

Meanwhile, researchers in several companies are working on other methods to lower HTT in those with Huntington’s disease.

  • One such method is called antisense oligonucleotides (ASOs) and is being developed by Roche. Wave Life Sciences is also using ASOs in WVE-003, which the company is testing in the Phase 1/2 SELECT-HD study (see NCT05032196).
  • Another method is called “splice modulators.” These drugs alter the way the genetic message is edited. Splice modulators such as branaplam were recently featured by HDBuzz. Novartis has been testing branaplam in the VIBRANT-HD study but dosing had to be suspended because of safety concerns.
  • PTC Therapeutics’ PTC-518 is also a splice modulator. It offers some similarity to branaplam but in actual comparison is quite different. Results of the PTC-518 trial should be available shortly.
  • Finally, gene therapy is the third option to lower HTT. You’ve already seen an example of this in the technology used by uniQure to develop AMT-130. The Phase 1/2 trial HD-Gene-TRX also tests AMT-130 for tolerability, safety, and dosage.

An Update

Currently, the three participants have either fully or partially recovered and have been released from the hospital. 

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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