Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease.
Alan H Nagahara, David A Merrill, Giovanni Coppola...
https://pubmed.ncbi.nlm.nih.gov/19198615Actively Recruiting
Phase 1
Age: 50Years - 80Years
All Genders
ID05040217
A Phase I Study to Assess the Safety, Tolerability and Preliminary Efficacy of AAV2-BDNF Gene Therapy in Early Alzheimer's Disease and Mild Cognitive Impairment
Led by Mark Tuszynski · Updated on 2025-10-21
12
Participants Needed
2
Research Sites
N/A
Total Duration
On this page
Sponsors
M
Mark Tuszynski
Lead Sponsor
O
Ohio State University
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating a gene therapy called AAV2-BDNF in people aged 50 to 80 years diagnosed with early Alzheimer's Disease or Mild Cognitive Impairment. This first-in-human Phase I trial aims to test whether the brain-delivered protein Brain-Derived Neurotrophic Factor (BDNF) can slow or prevent brain cell loss and activate healthy brain cells. The study uses a harmless virus to deliver the BDNF gene directly to brain cells, as BDNF cannot cross into the brain through the bloodstream. Participants will receive a single gene transfer procedure of AAV2-BDNF, an engineered virus designed to produce BDNF in the brain. The trial involves 12 participants, 6 with early Alzheimer's Disease and 6 with Mild Cognitive Impairment. No repeat dosing or daily medications are expected. The treatment is open-label, meaning all participants receive the gene therapy. During the 24-month study, participants will undergo evaluations including memory tests like the Ray Auditory Verbal Learning Task, Benson Complex Figure Draw, Mini-Mental State Exam, and Alzheimer's Disease Assessment Scale. Brain imaging with MRI and PET scans will monitor safety and biological effects. Biomarkers in cerebrospinal fluid will also be measured. Caregivers will assist by observing for adverse events and attending clinic visits. Safety and memory changes are the main outcomes assessed throughout the study.
CONDITIONS
Brief Title
A Clinical Trial of AAV2-BDNF Gene Therapy in Early Alzheimer's Disease and Mild Cognitive Impairment
Who Can Participate
Age: 50Years - 80Years
All Genders
Eligibility Criteria
You may qualify if you...
- Diagnosis of dementia due to Alzheimer's Disease by recognized criteria or diagnosis of Mild Cognitive Impairment due to Alzheimer's Disease
- Mini-Mental State Exam score between 22 and 29 depending on diagnosis
- Age between 50 and 80 years old
- No significant cerebral vascular disease (modified Hachinski score 3 4)
- EEG free of epileptiform abnormalities
- Stable permitted medications for at least one month prior to screening
- No depression according to Geriatric Depression Scale (score 3 8 on GDS-30)
- A caregiver available who has frequent contact and will accompany participant to all clinic visits
- Recent CT or MRI scan within 24 months without significant brain lesions or neurological disease
- Adequate visual and auditory ability for neuropsychological testing
- Good general health with no interfering diseases
- Normal or clinically insignificant serum B12, RPR, and thyroid tests
- ECG without abnormalities expected to interfere
- Women must be post-menopausal or surgically sterile (not pregnant or lactating)
You will not qualify if you...
- Significant neurological diseases other than suspected incipient Alzheimer's or Mild Cognitive Impairment
- Symptoms of aphasia making study assessments difficult
- Major psychiatric disorders or major depression within past two years
- Recent psychotic features, agitation, or behavioral problems
- History of alcohol or substance abuse within past two years
- History of schizophrenia
- Suicidal ideation or behavior in recent months
- History of systemic cancer within past 18 months (except some skin cancers)
- Significant or unstable systemic illnesses including recent heart attack, severe cardiovascular disease, pulmonary disease, gastrointestinal disorders, liver disease, uncontrolled diabetes or hypertension, coagulopathy, or hypothyroidism
- Use of excluded medications such as certain beta-blockers, narcotics, anti-Parkinsonian drugs, neuroleptics, benzodiazepines, corticosteroids, anticonvulsants, anticoagulants, or anti-amyloid monoclonal antibodies
- Use of investigational drugs within 30 days prior to treatment
- Contraindications to MRI or MRI contrast agents
- History of non-compliance with study procedures
- Prior gene therapy or RNA/DNA targeted Alzheimer's investigational treatments
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - One-time dosing
Participants receive a single gene transfer procedure of AAV2-BDNF gene therapy targeting early Alzheimer's Disease or Mild Cognitive Impairment.
1 treatment visit (in-person)
Follow-up
Duration - 24 months
Participants are monitored for safety, tolerability, and preliminary efficacy over 24 months following the gene therapy.
Multiple follow-up visits over 24 months
Trial Site Locations
Total: 2 locations
1
University of California - San Diego
La Jolla, California, United States, 92093
Actively Recruiting
2
The Ohio State University
Columbus, Ohio, United States, 43210
Actively Recruiting
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Research Team
A
Andrea Davis, MS
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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Published Research Related To This Trial
Potential therapeutic uses of BDNF in neurological and psychiatric disorders.
Alan H Nagahara, Mark H Tuszynski
https://pubmed.ncbi.nlm.nih.gov/21358740Early BDNF treatment ameliorates cell loss in the entorhinal cortex of APP transgenic mice.
Alan H Nagahara, Michael Mateling, Imre Kovacs...
https://pubmed.ncbi.nlm.nih.gov/24068826Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer Disease.
Mark H Tuszynski, Jennifer H Yang, David Barba...
https://pubmed.ncbi.nlm.nih.gov/26302439Growth Factor Gene Therapy for Alzheimer's Disease.
Mark H Tuszynski
https://pubmed.ncbi.nlm.nih.gov/39422960