As reported on InsidePrecisionMedicine, a new gene therapy aimed directly at the cells responsible for myelination is showing unprecedented promise for children with Canavan disease, a rare and fatal leukodystrophy. The disorder stems from mutations in the ASPA gene, causing toxic accumulation of N‑acetylaspartate (NAA) and progressive destruction of myelin in the central nervous system. Affected infants typically experience rapid neurological decline, culminating in severe disability and early death. Until recently, available treatments offered only supportive care.
A First-in-Class Strategy Focused on Oligodendrocytes In a Phase I/II clinical trial (NCT04833907), researchers evaluated MYR‑101, an investigational therapy using an engineered AAV vector (rAAV‑Olig001) designed to selectively target oligodendrocytes—the very cells responsible for forming and maintaining myelin. A one‑time intracerebroventricular infusion of the treatment was administered to 8 children, each living with Canavan disease.
Paola Leone, PhD, senior investigator and a long‑time leader in Canavan research, emphasized that the vector was developed to reach the exact cell population where the disease originates. She described the observed improvements in white matter growth and patient function as the most remarkable she has seen in decades of working with this disorder. Promising Improvements in Biomarkers and Development Follow‑up evaluations 12–24 months after injection demonstrated measurable and clinically relevant gains: More than 80% reduction in cerebrospinal fluid NAA levels, indicating restoration of ASPA enzyme activity. Significant increases in brain myelination, confirmed using advanced synthetic MRI techniques. Enhanced developmental performance based on the Mullen Scales of Early Learning.
Principal clinical investigator Robert Lober, MD, PhD, noted that these results suggest the therapy could shift the natural history of a condition once considered untreatable. All reported side effects were mild and resolved without long-term issues, and no serious complications linked to the therapy arose. Christopher Janson, MD, highlighted that quantitative myelin imaging—one of the tools used in the study—revealed biologically meaningful changes that reinforce the value of targeting oligodendrocytes directly. Regulatory Support and Broader Implications MYR‑101 and its underlying vector platform hold multiple expedited designations, including RMAT, Orphan Drug, Rare Pediatric Disease, and Fast Track status. The program is also part of the FDA’s START Pilot, an initiative to accelerate development of promising rare disease therapies.
These interim Phase I/II findings align with earlier data from the first treated cohort, which also showed sustained reductions in NAA and progressive gains in myelination and white matter volume. A Potential Turning Point for Leukodystrophy Treatment By correcting the metabolic defect within oligodendrocytes, MYR‑101 addresses the fundamental mechanism driving Canavan disease rather than providing only symptomatic benefit.
The research team believes this approach may lay the groundwork for new therapies targeting other inherited white matter conditions. As the clinical trial expands and longer-term data emerge, MYR‑101 could redefine expectations for gene therapy in demyelinating disorders—and offer a path toward meaningful disease modification for affected children and their families.
