MeiraGTx Announces Publication of New Research Identifying Underlying Mechanism of Functional Improvement Seen with AAV-GAD Gene Therapy in Parkinson’s Disease
December 12, 2018
Findings Published in Science Translational Medicine Show AAV-GAD Exerts Clinical Benefits by Inducing the Formation of New Brain Pathways
Results Expand on Findings from Completed Phase 2 Clinical Trial
LONDON and NEW YORK,
The publication, titled “Gene therapy reduces Parkinson’s disease symptoms by reorganizing functional brain connectivity,” can be accessed here.
“These new research findings provide important information about the mechanism of action of AAV-GAD and support its potential benefit in patients with Parkinson’s disease, who currently are limited to symptomatic treatments that do not modify the underlying disease process. The research also suggests that visualization of treatment-induced brain circuits can be useful in clinical trials in identifying treatment responses and providing insight into underlying biological mechanisms,” said
The Phase 2 study of AAV-GAD was the first successful randomized, double-blind, sham-controlled trial of its kind for a gene therapy product candidate targeting a brain disorder. Results were published in The Lancet Neurology in
To understand the effects of AAV-GAD therapy, a team of scientists from the
The research published in Science Translational Medicine showed that patients treated with AAV-GAD gene therapy developed a unique treatment-dependent metabolic brain network (termed the GAD-related pattern or GADRP), which reflected the formation of new functional pathways linking the STN to motor cortical regions. GADRP was characterized by increased metabolism in certain brain regions (i.e., the premotor region extending into the adjacent motor cortex and the supramarginal gyrus) along with relatively reduced metabolic activity in other brain regions (i.e., the thalamus, the caudate, the putamen/globus pallidus and the inferior frontal gyrus). The research also showed that the GADRP correlated with clinical improvement in the gene therapy-treated subjects as measured by changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) motor ratings (p<0.009). In contrast, the clinical correlation with sham surgery-related pattern was not significant (p=0.48).
AAV-GAD is an investigational gene therapy medicine designed to deliver the GAD gene to the STN in order to increase production of GABA, the primary inhibitory neurotransmitter in the human brain. GAD is the rate-limiting enzyme in the synthesis of GABA. Therefore, it is believed that increasing subthalamic nucleus GAD expression through gene therapy will result in normalization of motor circuits and improve symptoms in Parkinson’s disease patients without affecting other brain regions that can be responsible for complications associated with existing therapies.
AAV-GAD has received Fast Track designation from the
About the Phase 2 Study of AAV-GAD
The Phase 2 study included 45 patients with medically refractory Parkinson’s disease who were randomized 1:1 to receive either AAV-GAD gene therapy delivered by injection into the STN on both sides of the brain or bilateral sham surgery. Subjects were followed for one year, and all results remained blinded until the final treated patient reached the 6-month primary endpoint. The trial met the pre-specified, per-protocol primary endpoint, with a significant improvement in the off-medication motor section of the UPDRS part 3 compared to baseline. There was also a significant difference in the degree of improvement compared with patients in the sham arm. Other endpoints also showed significant improvements in AAV-GAD treated patients compared to patients in the sham arm.
In the study, AAV-GAD was well tolerated. No significant adverse events related to the therapy and no speech or cognitive complications were observed. The most commonly reported adverse events were transient mild or moderate headache (7 in treated arm vs. 2 in sham arm), nausea (6 in treated arm vs. 2 in sham arm) and worsening of Parkinson’s disease (0 in treated arm vs. 8 in sham arm).
About Parkinson’s Disease
Parkinson’s disease affects nearly 1 million Americans and 10 million people worldwide. Each year, 60,000 new cases of Parkinson’s disease are diagnosed in
(NASDAQ:MGTX) is a vertically integrated, clinical stage gene therapy company with four ongoing clinical programs and a broad pipeline of preclinical and research programs.
For more information, please visit www.meiragtx.com.
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i LeWitt PA, Rezai AR, Leehey MA, Ojemann SG, Flaherty AW et al. AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial. Lancet Neurol. 2011;10:309-319.