NCT05040217

A Clinical Trial of AAV2-BDNF Gene Therapy in Early Alzheimer's Disease and Mild Cognitive Impairment

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: Mark Tuszynski · Academic / Other
• Sex: All
• Age: 50 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Detailed 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 previous clinical programs of Nerve Growth Factor (NGF) gene therapy for AD and Neurturin gene therapy for Parkinson's disease in over 120 patients provided evidence that degenerating neurons respond to growth factors with classic "trophic" responses in the human brain. Participants will undergo one gene transfer procedure. Thus, dosing is performed only once, and repeat dosing or daily medications are not expected to be required. 12 participants will be enrolled in this Phase I trial, 6 with early AD and 6 with MCI.

Conditions

• Alzheimer's Disease
• Mild Cognitive Impairment

Interventions

Type	Name	Description
GENETIC	AAV2-BDNF Gene Therapy	AAV2-BDNF is a genetically engineered adeno-associated virus serotype 2 (AAV-2) that expresses the human BDNF cDNA.
BIOLOGICAL	AAV2-BDNF Gene Therapy	Gene therapy is a biological therapy delivering the BDNF gene to the brain

Timeline

• Start date: 2022-02-07
• Primary completion: 2027-12-01
• Completion: 2027-12-01
• First posted: 2021-09-10
• Last updated: 2025-10-21

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study