Our Clinical Trials

The therapies we have now brought to the clinic represent more than 20 years of effort between our group and our many collaborators. Collectively, we have dramatically advanced the technology of gene and drug delivery into the brain to make it more predictable, safer and efficacious. This is just the beginning of a new kind of medicine.

AAV2-hAADC for Primary AADC Deficiency in Pediatric Patients

We have gained FDA approval to undertake a clinical trial to treat a rare genetic disorder in which children are unable to make some important neurotransmitters, such as dopamine, norepinephrine and serotonin. This inability to synthesize these chemical signals is due to inactivating mutations in a gene called aromatic L-amino acid decarboxylase (AADC). Children with this disease are unable to move and have significant developmental disorders. In the study we plan to administer, a small nonpathogenic virus called AAV2 to carry a functional version of AADC into the neurons in the brain that make dopamine primarily. Although, this treatment will not treat all the symptoms of the disease, we hope that it will enable affected children to engage in more normal movements and perhaps experience other improvements in neurological function. Clinial trials will be performed at the University of California San Francisco (San Francisco, California, USA), National Institutes of Health (Bethesda, Maryland, USA) and University College London (London, United Kingdom). For more information, please follow these links:

AADC ResearchTrust | PND Assocation

Contact our administrators:
Waldy San Sebastian or John Bringas
Waldy.sansebastian@ucsf.edu or John.bringas@ucsf.edu | +1 415 502 1439

AAV2-hAADC for Parkinson's Disease

Parkinson's disease is a neurological disorder in which a major symptom involves difficulties with movement. Early in the disease, patients benefit from a number of medications, but the drug used most widely is L-Dopa (Sinemet). This drug is metabolized in the brain into the neurotransmitter, dopamine. When patients first start taking the drug, they usually respond well to the medication and can live for many years with good control over the movement disorder. As time goes by, L-Dopa works less well and patients have to take more drug with less and less predictable effect. In addition, high doses of the drug are associated with aberrant movements called dyskinesia. Many years of work in our laboratory convinced us that the failure of this otherwise effective drug was due fundamentally to the loss of the enzyme that converts L-Dopa to dopamine, aromatic L-amino acid decarboxylase (AADC). Our clinical strategy is to restore AADC to more normal levels in the part of the brain that degenerates most severely in Parkinson’s disease and thereby restore patients to a more normal L-Dopa response. We are infusing a small nonpathogenic virus called AAV2 carrying a functional version of the AADC gene into neurons in the putamen. We expect that patients who receive this recombinant virus will make more AADC and be able to convert L-Dopa into dopamine more efficiently. Our study is actively recruiting at UCSF and is supported by the Michael J. Fox Foundation. To find out more, please follow these links:

Michael J. Fox Foundation | ClinicalTrials.gov | Clinical Study Flyer
Contact our study coordinator:
Marin Thompson
thompsonme@neurosurg.ucsf.edu | +1 415 353 9666

AAV2-GDNF for Advanced Parkinson's Disease

Glial cell line-derived neurotrophic factor (GDNF) was first identified by its ability to promote the survival of embryonic DA neurons in vitro and further research has demonstrated beneficial effects of GDNF in animal models of PD. Our research team has accumulated convincing evidence that GDNF, properly delivered, has the ability to stimulate regrowth of the dopamine-producing neurons in the brain responsible for the movement disorder. We have developed a gene therapy in which a small nonpathogenic virus called AAV2 is being used to carry a functional version of GDNF into the neurons in the putamen, a part of the brain most affected by Parkinson’s disease. We are using a gene delivery technology developed in our laboratory that lets us monitor distribution of the virus by MRI as it is being infused into the putamen. The clinical trial is being performed at NIH Clinical Center in Bethesda, MD. More information about this currently recruiting trial may be found at ClinicalTrials.gov.

Contact our study coordinator:
Sandy Logan
sandy.logan@nih.gov | +1 301 451 8425

Convection-Enhanced Delivery of Recombinant GDNF Protein for Parkinson's Disease

As stated above, GDNF has potential to slow down or even reverse the course of Parkinson's disease. Since GDNF cannot be administered systemically due to its inability to enter the brain, we have been working for over the decade on research to help utilize GDNF full potential after local delivery to the brain. We developed MR-guided delivery of GDNF to the brain that allows us to assure that GDNF is administered correctly and we also were able to define intermittent dose schedule. Ongoing clinical trial in Parkinsonian patients utilizes repeated administration dosing protocol combined with MR imaging to assure optimal GDNF delivery to the brain. For more information please visit:  Parkinson's UK

Liposomal-Irinotecan In Recurrent High-grade Glioma (HGG)

Despite progress with combination therapies including surgery, radiation and/or chemotherapy, the treatment of HGG remains challenging with a typical median survival of 6-12 months for patients with newly diagnosed glioblastoma multiforme (GB) and 24-36 months for patients with anaplastic astrocytoma. One of the limitations of drug therapy for this kind of cancer is to achieve high enough concentrations of drug inside the tumor without encountering dose-limiting toxicity in the patients. An approach we have pioneered is to infuse suitably formulated drug directly into the tumor. We use intra-operative imaging (iMRI) to monitor infusions in order to achieve maximum coverage of the tumor by drug. The half-life of the drug is extended by encapsulating it in little droplets of fat, called liposomes, that sit in the tumor slowly releasing drug, in this case a drug called Irinotecan. Our currently recruiting clinical trial at UCSF is planned to acquire safety data with hopes of some efficacy for this lethal disease. For more information, please follow the link to ClinicalTrials.gov.

Contact our study coordinator:
Ashley DeSilva
desilvaaa@neurosurg.ucsf.edu | +1 415 353 2653