Gene Therapy: AADC - Phase I

Study Title:

A Phase I Open-label Safety Study of Intrastriatal Infusion of Adeno-Associated Virus Encoding Human Aromatic L-Amino Acid Decarboxylase (AAV-hAADC-2) in Subjects with Mid- to Late- Stage Parkinson’s Disease


This gene therapy trial investigated the safety and tolerability of administering AAV-hAADC-2 (adeno-associated virus with the inserted human gene for aromatic L-amino acid decarboxylase) in 10 subjects with moderate to advanced Parkinson's disease.  The secondary objectives were to determine the effect on clinical status and the relationship between the dose of infusion and the resulting level of striatal expression.  The clinical status was measured by subject diaries, clinical assessment, and the daily requirement of levodopa.  The expression level of the infused vector was measured by (18F) fluoro-meta-tyrosine (FMT) positron emission tomography (PET) imaging.    

The AADC gene codes for an enzyme in the brain that converts levodopa to dopamine.  In Parkinson's disease, AADC becomes less available as dopaminergic cells reduce, similar to dopamine. Over time, patients may require higher doses of levodopa, because the levodopa is not being converted to dopamine as efficiently. The study was designed to determine whether gene therapy with AADC benefited patients with Parkinson's disease. 

FMT PET scans showed an increase of AADC expression (30% in low dose cohort, 75% in high dose cohort) after 6 months and well-tolerated.

Publications based on the results of this study include: