Gene Therapy Shows Potential in Canavan Disease


Myrtelle’s therapy targets oligodendrocytes to deliver a functional copy of the ASPA gene.

Myrtelle’s recombinant adeno-associated virus (rAAV) vector-based investigational gene therapy has shown favorable safety and tolerability in the 3 patients dosed so far in the phase 1/2 first in-human clinical trial (NCT04833907) in Canavan disease.1

"All treated patients have exhibited favorable safety and tolerability to date. The gene therapy is administered via an intracerebroventricular route, and the post-procedure course has been in line with expected recovery in patients undergoing similar neurosurgical procedures. Based on the available data, the Data Monitoring Committee recommended opening the study to the younger cohorts: 15 to <36 months and 3 to <15 months old, as previously announced in January of this year,” co-principal investigator Robert Lober, MD, PhD, FAANS, associate professor of pediatrics, Wright State University Boonshoft School of Medicine, said in a statement.1

Lober is also an attending neurosurgeon at Dayton Children’s Hospital in Dayton, OH, where the trial is being conducted. The trial continues to recruit to an expected enrollment of 24 participants and additional patients will be enrolled in the second quarter of 2022. No treatment-related adverse events have been reported in the 3 patients treated so far in the first cohort, aged 3 to 5 years, and initial efficacy seems encouraging.

“We are encouraged by the initial findings in the 3 patients treated thus far in this landmark gene therapy trial in Canavan disease. These initial patients are between 36 to 60 months old, representing the oldest study cohort, and have now been followed for at least 6 months post-treatment. The efficacy measures include Gross Motor Function Measurement and the Mullen Scales of Early Learning as well as relevant biomarkers such as NAA levels and white matter and myelin content. We are looking forward to treating additional patients and moving forward with the clinical development of this novel gene therapy,” principal investigator Christopher Janson, MD, assistant professor of neuroscience, Wright State University Boonshoft School of Medicine, and director, Human Gene Therapy Center, Wright State Neuroscience Institute, added to the statement.

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The gene therapy is directed to target oligodendrocytes and deliver a functional ASPA gene to restore metabolism of N-Acetylaspartate in Canavan. All patients have received a single total dose of 3.7 x 1013 vg delivered by intracerebroventricular injection to target oligodendrocytes. Pfizer is developing and commercializing the gene therapy following an exclusive worldwide licensing agreement the companies entered into in 2021.

“We are encouraged by these early observations in the FIH trial supporting the hypothesis that delivery of a functional ASPA gene may lead to restoration of ASPA enzyme activity and improvements in biochemical and functional brain markers. The ongoing clinical trial is expected to continue to generate the critical data needed for further development of this novel gene therapy in the patients with Canavan disease,” Armen Asatryan, MD, MPH, chief medical officer, Myrtelle, added to the statement.1

Following encouraging safety and efficacy results, the Data Monitoring Committee (DMC) previously recommended opening the study to the two younger cohorts: 15 to 36 months of age and under 15 months, in January 2022.2

1. Myrtelle announces positive preliminary clinical data for its proprietary gene therapy in canavan disease. News release. Myrtelle. February 15, 2022.
2. Myrtelle announces successful completion of initial stage of phase 1/2 clinical trial of proprietary gene therapy for Canavan disease and expands treatment to younger patients. News release. Myrtelle. January 11, 2022. 
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