Myrtelle’s Canavan Disease Gene Therapy Effects Significant Decrease in CSF NAA and Increases in Brain Myelin Volume

According to new results from a phase 1/2 clinical trial (NCT04833907), Myrtelle’s rAAV-Olig001-ASPA (MYR-101), an investigational recombinant adeno-associated virus (AAV) vector-based gene therapy intended to treat Canavan disease, showed the ability to significantly decrease levels of N-Acetylaspartate (NAA) in the cerebrospinal fluid (CSF) and the ability to significantly increase brain myelin volume.¹

The findings were announced at the 2025 Cell & Gene Meeting on the Mesa, held October 5 to 7, in Phoenix, Arizona, and published in Nature Medicine. In addition to the decreases in NAA in the CSF, which Myrtelle noted is in line with restored function of the disease-targeted ASPA enzyme, and increases in brain myelin volume, which were indicated by Synthetic MRI, functional improvement was observed in the form of developmental progress seen in comparison to historical controls. Furthermore, Myrtelle pointed out that ongoing follow-up and is continuing to show potential for a durable effect from the gene therapy treatment.

With regard to safety, MYR-101 was characterized as “well-tolerated” with a “favorable safety profile”.¹ There were no serious adverse events reported that were deemed related to the treatment.

“These data represent a major step forward for children and families affected by Canavan disease,” said Michael Muhonen, MD, the cochiefmedical officer of Myrtelle, said in a statement.¹ “For the first time, we’re seeing clear biological and functional evidence that gene therapy targeting oligodendrocytes can directly address the core pathology of this disease.”

Notably, MYR-101 is 1 of 4 Center for Biologics Evaluation and Research (CBER)-regulated gene therapy programs that are part of the FDA’s Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program. MYR-101 has also previously received regenerative medicine advanced therapy (RMAT) designation, orphan drug designation (ODD), rare pediatric disease designation, and fast track designation from the FDA, ODD and advanced therapy medicinal product classification from the European Medicines Agency, and innovative licensing and access pathway designation from the United Kingdom’s Medicines and Healthcare products Regulatory Agency.

rAAV-Olig001-ASPA is not the only AAV vector-based gene therapy currently in development for Canavan disease. BridgeBio Pharma’s BBP-812, an AAV9 gene therapy that has also received RMAT designation from the FDA, is currently being evaluated for the treatment of Canavan disease in the phase 1/2 CANaspire clinical trial (NCT04998396).²

CGTLive® previously spoke to Florian Eichler, MD, a neurologist at Massachusetts General Hospital, about early data from the CANaspire trial he presented at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California.³ Eichler discussed the unmet needs in Canavan disease and how BBP-812 could potentially provide a transformative new treatment option for patients with the disease. He noted that the 6 children treated with BBP-812 in CANaspire up to that point had shown dramatic reductions in NAA levels in urine and highlighted behavioral observations of 1 patient who had begun sitting independently and taking steps.

“I think for the general practitioner, or the neurologist, who might be seeing these kinds of patients: early identification is key,” Eichler told CGTLive. “There are now trials that are available that are delivering safely a healthy copy of the gene. This has the potential to really allow for some of these children to attain milestones that have never been seen before. But it all requires timely diagnosis and referral to trial sites.”

REFERENCES
1. Myrtelle announces presentation of encouraging interim results from its phase 1/2 gene therapy trial for Canavan disease at the 2025 Cell & Gene Meeting on the Mesa. News release. Myrtelle Inc. October 6, 2025. Accessed October 13, 2025. https://myrtellegtx.com/myrtelle-announces-presentation-of-encouraging-interim-results-from-its-phase-1-2-gene-therapy-trial-for-canavan-disease-at-the-2025-cell-gene-meeting-on-the-mesa/
2. BridgeBio receives FDA’s regenerative medicine advanced therapy (RMAT) designation for BBP-812 Canavan disease gene therapy program. News release. BridgeBio Pharma, Inc. September 10, 2024. Accessed October 13, 2025. https://investor.bridgebio.com/news-releases/news-release-details/bridgebio-receives-fdas-regenerative-medicine-advanced-therapy
3. Eichler F, Nagy A, Laforet G, et al. Initialbiomarker and clinical findings from the CANaspire canavan disease gene therapy trial: exploration of connections between NAA and disease severity. Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA. Abstract #358.