Canavan-Single Patient IND

A recombinant virus vector constructed from adeno-associated virus (AAV) has been engineered to carry the human aspartoacylase (ASPA) gene expressed from a modified CMV-enhancer chicken β-actin (CB6) promoter. The construct has been shown to produce ASPA in animal models of Canavan disease, which closely match the proposed human study. The proposed clinical trial is an open label, expanded access study administering rAAV9-CB6-AspA gene vector by simultaneous systemic and intracerebroventricular routes to a single human subject (18-24 months of age) with Canavan disease. The subject will also receive immune modulation to transiently ablate B-cells (Rituximab) and modulate T-cell response (Sirolimus) prior to the initial exposure to AAV9. Given the null AspA mutations of the subject and current AAV seronegative status, this regimen will allow for later exposure to the therapeutic vector if needed and block any immuno-toxicity in the CNS. The goal of this study is to measure the safety and efficacy of AAV-mediated gene therapy as a treatment approach for neuronal pathology in Canavan disease. The subject will act as their own control and change from baseline will be assessed in regards to levels of brain NAA, brain water content and morphology, improved clinical status and peripheral levels of NAA. Safety parameters measured in this study will include: serum chemistries and hematology, urinalysis, physical assessments, whole blood assay for vector genomes, immunologic response to ASPA and AAV, as well as reported subject symptom history.