Skip Over Navigation Links

GMP Manufacture of AAV2-AADC for the Treatment of AADC Deficiency

The purpose of this project is to manufacture Good Manufacturing Practice (GMP) AAV2-AADC for use in a clinical trial of aromatic L-amino acid decarboxylase (AADC) gene therapy to ameliorate the symptoms of AADC deficiency, a rare genetic disorder in which the AADC enzyme 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. The investigators 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, the team requests support under the BrIDGs program to manufacture sufficient AAV2-AADC under GMP conditions to initiate the study.

Key Investigator

University of California, San Francisco
Krzysztof Bankiewicz, M.D., Ph.D.

Public Health Impact

The 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.

Outcomes

Approved studies are ongoing.

Project Details

  • Synthesis of GMP and non-GMP material
  • Formulation development
  • Pharmacokinetic/Absorption, Distribution, Metabolism, and Excretion (PK/ADME) studies
  • Investigational New Drug (IND)-directed toxicology

Contact

Tony Jackson