One person was given AMT-130 and the other a sham surgery as part of a control group. Both will now be followed for three months, after which a Data Safety Monitoring Board will determine the best steps for a next patient group.
“With the first two patients treated in this trial, we have taken a significant step forward in advancing AMT-130 closer to our goal of developing a therapy that inhibits the production of the mutant huntingtin protein. We are delighted to be working with leading experts in the field to evaluate this promising candidate,” Matt Kapusta, uniQure’s CEO, said in a press release.
AMT-130 is designed to inhibit production of the mutated form of the huntingtin (mHTT) protein, the underlying cause of Huntington’s disease.
This gene therapy is composed of a small portion of synthetic genetic material — called microRNA (miRNA) — that is carried and inserted into cells using an adeno-associated virus (AAV), which has been modified to be harmless.
Once inside a cell, the miRNA targets the RNA molecule that carries instructions to produce the huntingtin protein, and marks it for degradation. AMT-130 in this way should lower the production of abnormal huntingtin protein.
The five-year Phase 1/2 trial (NCT04120493) is evaluating the safety and proof of concept of AMT-130 in up to 26 Huntington’s patients with early symptomatic disease. The study is enrolling at six sites in the U.S.; contact and other information is available here.
Some patients will be randomized to either a low or high dose of AMT-130 given via an MRI-guided convention-enhanced delivery (CED), a surgical procedure that allows a single administration into a brain region called the striatum (involved in motor control, and a major site of lesions in Huntington’s). Others, part of a control group in this double-blind study, will undergo a sham procedure.
The trial’s primary goal is to assess therapy safety and tolerability. Additional (secondary) goals include evaluating levels of AMT-130 and mutant HTT in the brain, disease severity, and changes in motor and cognitive function.
“For years, uniQure has had an unwavering commitment to advance this first-in-human AAV gene therapy for Huntington’s disease into clinical testing,” Kapusta said.
In preclinical studies, a single administration of AMT-130 was seen to significantly lower the amount of mutant HTT in nerve cells derived from Huntington’s patients, as well as in mouse, mini-pig and nonhuman primate models of the disease.
“There is an urgent need for disease-modifying options to treat Huntington’s disease, and we’re excited to have an investigational gene therapy now available” for patients, said George Yohrling, chief scientific officer and chief mission officer at the Huntington’s Disease Society of America.
“Based on the promising preclinical data presented on AMT-130 over the years, we are optimistic about its potential to alter the course of this devastating disease,” he added.
AMT-130 has been granted orphan drug status and fast track designation — both supporting and advancing AMT-130’s development and potential approval for Huntington’s — by the U.S. Food and Drug Administration. It has also been designated an orphan medicinal product by the European Medicines Agency.
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