Parkinson’s gene therapy AB-1005 trial moves forward in Europe
Phase 2 trial participants randomly assigned to treatment groups
The first European patients in Askbio‘s Phase 2 clinical trial of AB-1005, an experimental gene therapy for Parkinson’s disease, have been randomly assigned to treatment groups.
The study, REGENERATE-PD (NCT06285643), has begun randomizing participants at sites in Poland and the U.K. Trial sites in Germany are “actively screening” and will follow soon, the company said.
“I believe the randomization of the first European participants in REGENERATE-PD, which makes this the first neurosurgical gene therapy program for Parkinson’s to successfully randomize patients from both the United States and Europe into a single Phase 2 trial, is positive news for people living with Parkinson’s disease and the physicians treating them,” Alan Whone, MD, PhD, professor at the University of Bristol and principal investigator and Europe lead on REGENERATE-PD, said in a company press release.
Parkinson’s is a progressive neurodegenerative disorder that damages dopaminergic neurons — the nerve cells responsible for producing dopamine, a key signaling molecule in the brain. As these cells are gradually lost, communication within the brain is disrupted, impairing the systems that control voluntary movement. This leads to motor symptoms such as tremors, muscle rigidity, and slowed movement.
AB-1005 is an investigational gene therapy that uses an adeno-associated virus 2 (AAV2) vector to deliver the GDNF gene directly to specific brain regions. The approach is designed to boost production of glial cell line-derived neurotrophic factor (GDNF), a protein essential for the survival and function of dopaminergic neurons.
Phase 1 trial shows promising results
AB-1005 is administered directly into the putamen, a brain region critical for motor control, via an MRI-guided neurosurgical injection. Once delivered, target brain cells use the introduced gene to continuously produce GDNF to alleviate motor symptoms.
In a Phase 1 clinical trial (NCT04167540), AB-1005 eased motor symptoms in people with moderate Parkinson’s. About three years after surgery, there was a trend toward improvement or stabilization of motor function in these participants. They also required less levodopa, a first-line Parkinson’s therapy, for motor control.
The gene therapy showed signs of stabilizing disease progression in patients with mild forms of Parkinson’s.
The therapy was well tolerated, and researchers reported no serious safety concerns related to AB-1005. The most common side effects included mild headache or fatigue related to the surgery.
REGENERATE-PD will build on these findings in a larger group of participants, testing the treatment in approximately 87 patients aged 45-75 with moderate-stage Parkinson’s. Some will receive AB-1005, and others will receive the surgical equivalent of a placebo.
The trial’s main goal will be changes in motor function over the 18 months (about 1.5 years) after surgery. Participants will record their off times, when levodopa cannot adequately control motor symptoms, and on times, when treatment effectively manages symptoms without troublesome side effects.
“We are encouraged by the initiation of the REGENERATE-PD program in Europe and look forward to sharing further clinical updates as the program advances over the coming year,” said Canwen Jiang, MD, PhD, chief development officer and chief medical officer at Askbio.
U.S. and U.K. regulators have granted the gene therapy designations designed to accelerate its development and review. The U.S. Food and Drug Administration also gave AB-1005 regenerative medicine advanced therapy status, which can support expedited review for therapies that address serious or life-threatening diseases.
In addition to the Parkinson’s trials, a Phase 1 study (NCT04680065) is testing the gene therapy as a treatment for multiple system atrophy, a form of atypical parkinsonism.
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