The purpose of this project is to manufacture cGMP AAV2-AADC for use in a clinical trial of AADC gene therapy to ameliorate the symptoms of AADC deficiency, a rare genetic disorder in which the enzyme, aromatic L-amino acid decarboxylase (AADC), is inactive due to structural mutations in the gene. We have previously shown that AAV2-AADC, when delivered into the putamen of patients with Parkinson's disease, restores effective levels of the enzyme and enhances dopaminergic function. We plan to use the same strategy to restore AADC function in children with AADC deficiency. The clinical study is envisaged to take place at NIH Clinical Center. Accordingly, we request support under the RAID program to manufacture sufficient AAV2-AADC under GMP conditions to initiate the study.

Public Health Relevance

AADC deficiency disease is a rare, recessive genetic disease that exacts a considerable toll on the lives of those it afflicts. In addition, like many genetic diseases (especially those with neurological deficits), the cost of caring for such patients is extremely high. This is why the NIH has made the development of treatments of such diseases a high priority. Our proposed gene therapy for AADC deficiency disease, if successful, should ameliorate many of its central neurological symptoms. The use of a new, advanced targeting and delivery technology may also be applicable to a number of other neurological disorders that would benefit from neurosurgical delivery of therapeutic agents.

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