AADC deficiency is a genetic disorder. It is caused by errors, or mutations, in the gene for AADC. The gene mutations lead to malfunction of the AADC protein. AADC is an enzyme that is essential for the production of specific chemical signaling molecules, or neurotransmitters: dopamine, serotonin, norepinephrine, and epinephrine. When AADC does not work properly, a person cannot produce normal levels of these neurotransmitters. Symptoms result from a state of neurotransmitter deficiency in the brain and the body. The purpose of this gene transfer study is to test a new, experimental treatment for AADC deficiency. The intervention will attempt to provide corrected copies of the human gene for AADC (hAADC) directly into brain cells in one specific region of the brain, the midbrain. The gene will be introduced via a gene vector, which is a specially modified virus (adeno-associated virus type 2, AAV2) that can carry the gene into brain cells. The gene and the vector are combined to make the gene transfer agent, known as AAV2-hAADC. The procedure will involve direct injections of AAV2-hAADC into the brain. Once the gene is inside brain cells, we expect that the body will use its own natural mechanisms of making proteins to make functional AADC enzyme.

Public Health Relevance

This first-in-children clinical trial aims to partially correct a genetic deficiency of a key enzyme (AADC) needed to synthesize certain key neurotransmitters (Dopamine, Norepinephrine, and Serotonin) in the brain. Children with AADC Deficiency require constant care that exacts a disproportionate economic, social and human cost on society. The proposed intervention will deliver a recombinant adeno-associated virus carrying the human AADC gene into the dopamine-producing cells in the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS094292-04
Application #
9729853
Study Section
Special Emphasis Panel (ZNS1)
Program Officer
Morris, Jill A
Project Start
2016-08-01
Project End
2020-06-30
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118