A Phase I Study to Assess the Safety, Tolerability and Preliminary Efficacy of AAV2-BDNF [Adeno-Associated Virus (AAV)-Based, Vector-Mediated Delivery of Human Brain Derived Neurotrophic Factor] in Subjects With Early Alzheimer's Disease and Mild Cognitive Impairment
Mark Tuszynski
Summary
This is a first-in-human clinical trial to test whether a protein administered into the brain continuously by gene therapy, Brain-Derived Neurotrophic Factor (BDNF), will slow or prevent cell loss in the brains of people affected by Alzheimer's disease and Mild Cognitive Impairment. The protein may also activate cells in the brain that have not yet deteriorated. Gene therapy refers to the use of a harmless virus to have brain cells make the potentially protective protein, BDNF.
Description
This is an open label Phase I clinical trial of AAV2-BDNF gene therapy for early Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) in 12 participants. BDNF is a nervous system growth factor that regulates neuronal function in key memory circuits of the brain (the entorhinal cortex and hippocampus). BDNF reduces cell loss, stimulates cell function, and builds new connections (synapses) between brain cells in animal models. This clinical trial will use techniques of gene therapy because the candidate therapeutic protein, BDNF, does not cross the blood brain barrier (BBB). Two previo…
Eligibility
- Age range
- 50–80 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: Specific inclusion criteria will be as follows for patients 1-6 (Mild AD dementia): 1. Diagnosis of dementia due to Alzheimer's Disease (AD) by National Institute of Aging (NIA) - Alzheimer's Association (AA) criteria for AD 15. The diagnosis of probable AD according to NIA criteria 15 is internationally recognized as the "gold standard" for diagnosing AD. 2. Mini-Mental State Exam score between 22 and 28 (inclusive). 3. No significant cerebral vascular disease: modified Hachinski score of ≤ 4. 4. Age 50 - 80 years old. 5. EEG is free of epileptiform abnormalities. 6. Per…
Interventions
- GeneticAAV2-BDNF Gene Therapy
AAV2-BDNF is a genetically engineered adeno-associated virus serotype 2 (AAV-2) that expresses the human BDNF cDNA.
- BiologicalAAV2-BDNF Gene Therapy
Gene therapy is a biological therapy delivering the BDNF gene to the brain
Locations (2)
- University of California - San DiegoLa Jolla, California
- The Ohio State UniversityColumbus, Ohio