Canavan Disease Gene Therapy Continues to Show Promise


No serious adverse events related to the gene therapy have been reported.

Myrtelle’s rAAV-Olig001-ASPA (MYR-101), an investigational recombinant adeno-associated virus (rAAV) vector-based gene therapy intended to treat Canavan disease (CD), has continued to show promising efficacy and safety in interim data from its phase 1/2 clinical trial (NCT04833907).1

rAAV-Olig001-ASPA is directed at oligodendrocytes and is intended to restore function of ASPA, the disease targeted enzyme. Myrtelle announced in October 2022 that dosing of the first 8 patients in the clinical trial had been completed.2 All of these patients have now reached at least 3 months of follow-up, and the results from this timepoint showed increases in white matter, grey matter, and total brain volumes, along with decreases in the volume of cerebrospinal fluid (CSF) in most patients, as measured by MRI.1 Furthermore, improvements across several domains were reported in clinical measurements of motor and cognitive function with the Gross Motor Function Measure (GMFM) and Mullen Scales of Early Learning (MSEL) tools.

The first 3 patients treated in cohort 1, which includes those older than 36 months, are now at 18 months or more post-treatment. It was previously reported that at 6-months of follow-up, these patients improved on the GMFM and the MSEL and showed brain white matter and myelin content increases.2 In terms of safety, no serious adverse events related to the gene therapy have been reported to date.1

"The early results to date in patients treated in Myrtelle’s phase 1/2 clinical trial are encouraging,” Rob Lober, MD, principal investigator on the study, Attending Neurosurgeon at Dayton Children’s Hospital, and Associate Professor of Pediatrics at Wright State University Boonshoft School of Medicine, said in a statement regarding the news.1 “The available evidence suggests the delivered gene therapy is, within 3 months, rapidly eliciting its intended effect. Given these data, we are encouraged to continue tracking these treated patients and to advance development of the candidate gene therapy to bring this potential treatment option to CD patients.”

rAAV-Olig001-ASPA was previously granted rare pediatric disease and fast track designations by the FDA in March 2022.4 In September 2022, rAAV-Olig001-ASPA was granted Advanced Therapy Medicinal Product (ATMP) classification by the European Medicines Agency (EMA).3 It has also received orphan drug designations from both the FDA, in March 2022, and the EMA, in December 2022.1,5

“One key objective of gene therapy in Canavan disease is to restore myelin and enable its function in the patient’s brain,” Christopher Janson, principal investigator of the trial, stated in a Q&A published by the company last month.6 “In the clinical trial, we are measuring myelin and white matter using non-invasive, advanced magnetic resonance imaging. At the same time, levels of brain N-Acetylaspartate (NAA) are also monitored. We know from prior studies that even a very modest decrease in NAA may be sufficient to prevent and repair damage to the myelination process. Because NAA levels can vary regionally in the brain, global NAA levels in the brain can be difficult to interpret. In my view, affecting the NAA levels where it matters the most, in the brain of the patient, is a unique aspect of our gene therapy approach as we use a direct route of administration to the brain.”

1. Myrtelle announces positive interim data in phase 1/2 clinical trial of its proprietary investigational gene therapy raav-olig001-aspa in canavan disease. News release. Myrtelle Inc. January 9, 2023. 
2. Myrtelle completes dosing of 8 patients with canavan disease in its phase 1/2 clinical trial of the investigational gene therapy rAAV-Olig001-ASPA. News release. Myrtelle Inc. September 20, 2022. 
3. Myrtelle’s rAAV-Olig001-ASPA gene therapy candidate for canavan disease receives advanced therapy medicinal product classification from the european medicines agency. News release. Myrtelle Inc. September 7, 2022. 
4. Myrtelle Receives FDA Fast Track, Rare Pediatric Disease, and Orphan Drug Designations for its proprietary gene therapy for the treatment of Canavan disease. News release. Myrtelle. March 15, 2022. 
5. Myrtelle’s rAAV-Olig001-ASPA gene therapy candidate for canavan disease receives orphan drug designation from the European Medicines Agency. News release. Myrtelle Inc. December 14, 2022. 
6. Dr. Christopher Janson, the Principal Investigator on Myrtelle’s Canavan Disease gene therapy trial, addresses questions frequently asked by the families in relation to the disease and gene therapy. News release. Myrtelle Inc. December 14, 2022. 
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