MeiraGTx Holdings plc's AAV-GAD gene therapy has shown promising results in a Phase I/II trial for Parkinson's disease, meeting its primary endpoint of safety and tolerability. The sham-controlled bridging study, which involved 14 patients across three arms (high-dose, low-dose, and sham control), demonstrated a statistically significant improvement in motor function for the high-dose group.
Key Findings from the Phase I/II Trial
The study evaluated the AAV-GAD therapy over 26 weeks. The high-dose group (n=5) experienced an average improvement of 18 points in their 'off' score on the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III, a key measurement for Parkinson's disease. According to Alexandria Forbes, president and CEO of MeiraGTx, a change of five to 10 points is considered clinically meaningful, underscoring the substantial impact of the AAV-GAD treatment.
Both the low-dose (n=5) and sham groups (n=4) did not show significant changes in their scores. However, both the high- and low-dose groups demonstrated significant improvements in quality of life, as indicated by the Parkinson’s Disease Questionnaire (PDQ-39) scores. The high-dose group improved by eight points from baseline, while the low-dose group improved by six points. In contrast, the sham group experienced a slight worsening of 0.2 points.
Dr. Ali Rezai, the study's principal investigator, noted that the safety and outcome results were excellent, with motor score improvements and significant quality of life improvements being very encouraging for both patients and physicians.
AAV-GAD Mechanism of Action
AAV-GAD delivers the glutamic acid decarboxylase (GAD) enzyme to the subthalamic nucleus in the brain. This enzyme catalyses the conversion of glutamic acid into gamma-aminobutyric acid (GABA), which helps alleviate the dysfunction of the subthalamic nucleus and, in turn, reduces motor symptoms associated with Parkinson's disease. The therapy is administered as a one-time infusion through a minimally invasive procedure that does not require general anaesthesia.
Future Directions
MeiraGTx plans to initiate a Phase III study in 2025, following discussions with regulators in the US, Europe, and Japan. The company reports that no AAV-GAD-treated subjects experienced worsening Parkinson’s disease as an adverse event. To date, AAV-GAD has been administered to 58 patients across three independent studies.
Parkinson's Disease Context
Parkinson's disease affects approximately 10 million people worldwide and is the second most common neurodegenerative disease after Alzheimer's. While many patients initially respond to dopamine therapy, the effectiveness of these treatments decreases over time, with around half of Parkinson's patients experiencing ineffective oral therapy within five years. Long-term use of dopamine therapy is also associated with complications such as levodopa-induced dyskinesia and motor fluctuations, highlighting the need for alternative treatments.
