Parkinson’s gene therapy safe, appears to ease motor symptoms
After positive Phase 1 trial results, Phase 2 study of AB-1005 now underway
Treatment with Askbio‘s gene therapy candidate AB-1005 is safe and appears to ease motor symptoms in people with either a recent or a long-standing diagnosis of Parkinson’s disease.
That’s according to the full results of a small Phase 1 clinical trial conducted by the gene therapy’s developer at three sites in the U.S.
Based on the positive data from that Phase 1 study, Askbio is now running a Phase 2 clinical trial called REGENERATE-PD (NCT06285643). That trial, which is enrolling an estimated 87 adults with moderate Parkinson’s, aims to test AB-1005 against a sham procedure.
Participants, ages 45 to 75, are being recruited at study centers across the U.S., Poland, and the U.K.; additional sites will be opening in Germany, and in all countries except the U.K. Eligible patients will have been diagnosed with Parkinson’s in the past 4-10 years.
Askbio announced top-line results from the Phase 1 trial in early 2024 and presented the findings at a scientific conference later that year. The full results are now detailed in a paper titled “Intraputaminal Delivery of Adeno-Associated Virus Serotype 2-Glial Cell Line-Derived Neurotrophic Factor in Mild or Moderate Parkinson’s Disease,” published in the journal Movement Disorders. The work was funded by Askbio. Five of the study’s 11 authors are Askbio employees.
In Parkinson’s disease, nerve cells in the brain that are responsible for making the chemical messenger dopamine sicken and die. AB-1005, also known as AAV2-GDNF, is designed to deliver to brain cells a version of the gene encoding the signaling molecule GDNF — fully known as glial cell line-derived neurotrophic factor — which promotes the survival of dopamine-making nerve cells. The gene therapy is designed to be given by a surgical procedure directly into the putamen, a region of the brain that’s heavily affected by Parkinson’s.
Full results now shared for small Phase 1 trial testing AB-1005
In the Phase 1 clinical trial (NCT04167540), 11 adults with Parkinson’s were treated with AB-1005. Six of the participants had mild Parkinson’s while the other five had moderate disease; nearly three-quarters of the patients were male and the average age was in the mid-50s. Trial participants continued to receive standard Parkinson’s treatments like levodopa in addition to the gene therapy.
All were monitored for an initial period of 18 months, and are continuing to be monitored for a longer period of five years.
The study’s main goal was to assess the safety of AB-1005, and the results, overall, were positive. No serious safety issues related to the gene therapy were reported. One patient experienced a serious complication of reduced blood flow in the brain, which was deemed as potentially related to the surgical procedure used to administer the therapy. The most common safety issues noted were non-serious headache or fatigue related to the surgery, which generally resolved within a month after the procedure.
“This Phase 1b study met the primary objective and shows the safety of [AB-1005] in participants with mild or moderate [Parkinson’s disease] through 18 months posttreatment,” the researchers wrote.
Imaging data showed the gene therapy successfully delivered GDNF to about two-thirds of cells in the putamen.
[These data indicate that AB-1005] may provide a beneficial disease-modifying effect in the form of stabilization or restoration in the mild and moderate [Parkinson’s] cohorts [patient groups], respectively.
Assessments of motor function showed that, among patients with mild Parkinson’s, motor symptom severity was generally unchanged after 18 months of follow-up. This marks a notable contrast to the typical trajectory of Parkinson’s, in which symptoms generally get worse over time.
For patients with moderate disease, motor symptoms tended to get less severe over 18 months of follow-up, the researchers noted. Importantly, the reduction in motor symptom severity was seen even when patients were assessed without the influence of other meds like levodopa.
Daily off time down, on time up with Parkinson’s gene therapy
In this group of patients, daily off time, or periods when symptoms are not adequately controlled, decreased by 1.7 hours. Daily good on time — time with better symptom control — increased by 2.2 hours. The levodopa equivalent daily dose, a measure of the total daily amount of Parkinson’s medications, also was reduced, per the study results.
Assessments of nonmotor symptoms were generally unchanged over 18 months following AB-1005 treatment in both the mild and moderate groups, according to the researchers.
Collectively, the researchers concluded, these data indicate that AB-1005 “may provide a beneficial disease-modifying effect in the form of stabilization or restoration in the mild and moderate cohorts [patient groups], respectively.”
The scientists noted, however, that this was a small study with a fairly short follow-up time, and also that there was no placebo group. That latter factor makes it impossible to rule out the placebo effect when interpreting the results. As such, the researchers stressed that further clinical trials like REGENERATE-PD are needed to assess the efficacy of AB-1005 for Parkinson’s disease.
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