RARE Daily

Myrtelle Reports Positive Six-Month Post-Treatment Data from Gene Therapy Trial in Canavan Disease

April 19, 2023

Rare Daily Staff

Myrtelle reported encouraging initial data and a favorable safety profile at the six-month, post-treatment time point in the eight patients treated with the company’s experimental gene therapy in its phase 1/2 first-in-human clinical trial for Canavan disease, a fatal genetic brain disorder in children.

Canavan disease (CD) is a fatal childhood genetic brain disease in which mutations in the aspartoacylase gene (ASPA) prevent the normal expression of aspartoacylase (ASPA), a critical enzyme produced in oligodendrocytes that breaks down the neurochemical N-acetylaspartate (NAA). When not properly metabolized by oligodendrocytes, NAA accumulates in the brain and negatively affects bioenergetics, myelin production, and brain health. Patients with CD are impacted at birth but may appear normal until several months old when symptoms begin to develop. Poor head control, abnormally large head size, difficulty in eye tracking, excessive irritability, severely diminished muscle tone, and delays in reaching motor milestones, such as rolling, sitting, and walking, are the typical initial manifestations of CD. As the disease progresses, seizures, spasticity, difficulties in swallowing, and overall muscle deterioration emerge with most affected children developing life-threatening complications by approximately 10 years of age. Currently, there are no cures for CD, and only palliative treatments are available.

Myrtelle’s clinical trial utilizes the company’s proprietary rAAV vector to directly target oligodendrocytes, the brain cells affected in CD that are responsible for producing myelin—the insulating material that enables proper neuronal function. The oligodendrocyte-targeting rAAV vector-based gene therapy is intended to restore ASPA function and hence the metabolism of NAA and brain development in patients with CD.

Trial assessments showed statistically significant mean absolute and/or percent increases from baseline measurements in myelin, white matter, grey matter, and total brain volume, and reduction in the volume of cerebrospinal fluid by magnetic resonance imaging in these patients. Additionally, clinical measurements of motor and cognitive function using the Gross Motor Function Measure and Mullen Scales of Early Learning demonstrated mean absolute and percentage improvements across multiple domains. In several domains, the observed improvement in treated patients is in contrast to the observed deterioration in untreated age-matched CD patients within Myrtelle’s natural history data set. No serious drug-related adverse events have been observed to date.

“The six-month functional and anatomic data observed in these patients are encouraging in showing positive changes in the patients’ motor, language, cognitive and visual skills.” said Chris Janson, principal investigator and director of Human Gene Therapy Center at Wright State Neuroscience Institute in Dayton, Ohio. “Improvements in functional scores were observed across multiple domains on the GMFM and MSEL assessment tools. In addition, volumetric MRI measurements showed increases in multiple brain tissue compartments and reductions in CSF volume. Reductions in brain NAA, measured by magnetic resonance spectroscopy were also seen. These improvements suggest the gene therapy is having its intended effect and encourages advancement of the gene therapy program to bring this potential treatment option to more CD patients.”

An update on the trial at a symposium will be presented at the ASGCT 26th Annual Meeting in Los Angeles in May.


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