Canavan Disease (CD)
https://www.nature.com/articles/s41591-025-03919-w
Canavan disease (CD) is a rare inherited neurological disorder caused by mutations in the ASPA gene. When ASPA is missing, a compound called NAA (N-acetylaspartate) builds up and damages oligodendrocytes, the cells that make myelin. This article reports the first-in-human phase 1/2 clinical trial testing a new gene therapy called MYR-101 (rAAV/Olig001-ASPA) to replace the lacking ASPA gene specifically in oligodendrocytes. Eight children with genetically confirmed CD (aged 1 to 5 years) received a single dose delivered directly into their brains and were followed for about 12 months. Although all children experienced some side effects, none were related to the treatment itself but rather to the surgical procedure, suggesting that the gene therapy was safe. Importantly, brain and spinal fluid tests showed a drop in toxic NAA levels, and brain scans revealed improved myelin formation, indicating that the introduced ASPA gene was expressed and functional. Clinically, most participants showed stable or improved cognitive and motor functions compared with typical data from untreated individuals. These results show that it is possible to safely deliver functional ASPA to the targeted brain cells, reduce harmful buildup and restore myelin. Although longer-term follow-up is needed to confirm the durability of the treatment, the findings provide the first proof-of-concept that gene therapy can change the course of CD.