Myrtelle Reports Major NAA Reduction in Phase 1/2 Gene Therapy Trial for Canavan Disease

Myrtelle Inc., a gene therapy company focused on neurodegenerative diseases, has released promising data from its clinical trials for Canavan disease (CD). Canavan disease is a severe genetic disorder caused by mutations in the ASPA gene, leading to impaired brain development and myelination due to deficient aspartoacylase enzyme production. This enzyme deficiency prevents the normal metabolism of N-Acetylaspartate (NAA), which is crucial for myelin synthesis and brain bioenergetics. Symptoms of CD appear within the first few months of life and include poor motor skills, large head size, and muscle deterioration, eventually leading to severe complications by around ten years of age. Currently, no cures exist for CD, and treatments available only offer palliative care.

The clinical trial results from Myrtelle’s investigational gene therapy, rAAV-Oligo001-ASPA, have shown notable biomarker changes in patients. Conducted at Dayton Children’s Hospital in Ohio, the open-label Phase 1/2 First-in-Human (FIH) trial involves baseline and post-treatment assessments over a period extending up to five years. Seven patients receiving the treatment demonstrated a reduction of more than 80% in NAA levels from their baseline measurements within 24 months post-treatment. Additionally, Magnetic Resonance Imaging (MRI) assessments revealed increases in brain white matter and myelin volume, indicating improvements in myelination.

Myrtelle’s approach employs a proprietary rAAV vector that specifically targets oligodendrocytes, the brain cells responsible for myelin production. By restoring the ASPA enzyme function through gene therapy, the treatment aims to correct the metabolic pathway that is disrupted in CD, thereby normalizing NAA metabolism and promoting myelination.

Moreover, patients exhibited functional improvements measured by validated clinical scales. This is particularly significant given that the natural progression of CD typically leads to continuous clinical deterioration. These improvements in NAA levels, myelin volume, and patient functionality are being viewed as strong indicators of the therapy’s potential efficacy and safety.

Olga Flamini, Co-Chief Medical Officer at Myrtelle, expressed optimism about the findings, emphasizing that the observed changes in critical disease markers and patient functionality are highly encouraging. Flamini noted that these results motivate the company to continue its efforts to make this potentially life-saving therapy available to patients who currently have no effective treatment options.

The investigational therapy, rAAV-Oligo001-ASPA, has garnered significant regulatory attention and support. It has been selected by the FDA for the START pilot program and has received multiple designations, including RMAT, Orphan Drug, Rare Pediatric Disease, and Fast Track designations from the FDA. Additionally, it has been classified as an Advanced Therapy Medicinal Product (ATMP) by the European Medicines Agency and has received the Innovative Licensing and Access Pathway (ILAP) designation from the UK Medicines & Healthcare products Regulatory Agency.

Myrtelle, leveraging its proprietary platform and innovative gene therapy approaches, aims to develop transformative treatments for neurodegenerative diseases. The company’s exclusive worldwide licensing agreement with Pfizer Inc. for its Canavan disease program underscores its commitment to addressing unmet medical needs in this field.

The ongoing clinical trial and the positive preliminary results are paving the way for further development and discussions with regulatory authorities to establish a potential road map for the registration of rAAV-Olig001-ASPA as a viable treatment option for Canavan disease.