A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC
The purpose of this study is to determine whether AAV2-hAADC gene therapy is safe and effective in the treatment of aromatic amino acid decarboxylase (AADC) deficiency.
Aromatic Amino Acid Decarboxylase Deficiency
Genetic: gene therapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC|
- Serious intracerebral hemorrhage that requires surgical management [ Time Frame: Post-operative day 0 (CT) and day 3 (MRI) ] [ Designated as safety issue: Yes ]A CT scan will be done immediately after surgery and an MRI scan will be done around 3 days after the surgery. Any intracerebral hemorrhage will be evaluated to see if a surgical decompression will be necessary
- Improvement of PDMS-2 score [ Time Frame: 12th month post surgery ] [ Designated as safety issue: No ]PDMS-2 will be performed before and 12 months after the surgery, and the two scores will be compared
- CSF neurotransmitter levels [ Time Frame: 12th month post surgery ] [ Designated as safety issue: No ]A lumbar puncture will be performed both before the surgery and 12 months after surgery. HVA and HIAA levels will be measured and compared.
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||March 2015|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Experimental: Gene therapy
Intracerebral infusion of AAV2-hAADC viral vector will be performed
Genetic: gene therapy
AAV2-hAADC viral vector will be injected into bilateral putamen by stereotactic surgery.
Other Name: Intracerebral infusion of AAV2-hAADC viral vector
Aromatic L-amino acid decarboxylase (AADC) is an enzyme responsible for the final step in the synthesis of neurotransmitters dopamine and serotonin. AADC deficiency is a very rare genetic disorder, but Taiwanese (or Chinese) carry a high prevalence of AADC deficiency due to a founder mutation and patients usually die before the age 5-6 years due to severe motor dysfunction. Gene therapy with adeno-associated virus (AAV) serotype 2 (AAV2) driven human AADC (hAADC) has been tested in Parkinson disease. A compassionate treatment of 4 patients with AADC deficiency by AAV2-hAADC has demonstrated good safety and efficacy. The viral vector will be produced by a GMP facility. Viral vector will be injected directly to bilateral putamens by stereotactic surgery. The safety of the surgery will be monitored by both computed tomography (CT) and magnetic resonance imaging (MRI). Efficacy of the treatment will be monitored by positron emission tomography (PET), cerebral spinal fluid (CSF) neurotransmitter metabolites homovanillic acid (HVA) and 5-Hydroxyindoleacetic acid (5-HIAA) levels, and motor and mental developmental scores.
|Contact: Wuh-Liang Hwu, MD||886-2-23123456 ext firstname.lastname@example.org|
|Contact: Vicky Wu, MS||886-2-23123456 ext email@example.com|
|National Taiwan University Hospital||Not yet recruiting|
|Taipei, Taiwan, 100|
|Contact: Wuh-Liang Hwu, MD 886-2-23123456 ext 71938 firstname.lastname@example.org|
|Principal Investigator: Wuh-Liang Hwu, MD|
|Principal Investigator:||Wuh-Liang Hwu, MD||Department of Pediatrics and Medical Genetics, National Taiwan University Hospital|