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

Sponsor

Mark Tuszynski (Other)

Overall Status

Recruiting

CT.gov ID

NCT05040217

Collaborator

Case Western Reserve University (Other), Ohio State University (Other)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Genetic: AAV2-BDNF Gene Therapy Biological: AAV2-BDNF Gene Therapy	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This study aims to reduce neuronal loss and rebuild synapses in the brain of patients with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI). A total of 12 subjects will be enrolled: subjects 1-6 will have a diagnosis of AD and subjects 7-12 will have a diagnosis of MCI. The gene therapy vector will consist of adeno-associated virus serotype 2 (AAV2) and will be stereotaxically administered into the brain under MRI guidance. Subjects will be followed over a pre-determined study time duration of 24 months, and indefinitely thereafter.This study aims to reduce neuronal loss and rebuild synapses in the brain of patients with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI). A total of 12 subjects will be enrolled: subjects 1-6 will have a diagnosis of AD and subjects 7-12 will have a diagnosis of MCI. The gene therapy vector will consist of adeno-associated virus serotype 2 (AAV2) and will be stereotaxically administered into the brain under MRI guidance. Subjects will be followed over a pre-determined study time duration of 24 months, and indefinitely thereafter.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 1, 2021

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gene transfer of AAV2-BDNF Up to 12 subjects will receive open-label AAV2-BDNF	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 Other Names: Growth Factor Gene Therapy

Arm

Intervention/Treatment

Experimental: Gene transfer of AAV2-BDNF

Up to 12 subjects will receive open-label AAV2-BDNF

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

Other Names:

Growth Factor Gene Therapy

Outcome Measures

Primary Outcome Measures

Safety as assessed by mumber of participants with treatment-related adverse events assessed on MRI scan [24 months]
Number of participants with treatment-related adverse events assessed on MRI scan
Memory change tested on Ray Auditory Verbal Learning Task [24 months]
Memory tested on Ray Auditory Verbal Learning Task
Memory change tested on Benson Complex Figure Draw and Memory [24 months]
Memory tested on Benson Complex Figure Draw and Memory

Secondary Outcome Measures

Efficacy on PET scan reflected by change in fluorodeoxyglucose (FDG) PET scan [24 months]
FDG PET scan
Change in Biomarkers including CSF amyloid, tau and neurofilament [24 months]
CSF studies of amyloid, tau and neurofilament
Memory change tested on mini-mental status examination (MMSE) [24 months]
MMSE
Memory tested on Alzheimer's Disease Assessment Scale, Cognitive component (ADAS-Cog) [24 months]
ADAS-Cog

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

diagnosis of probable Alzheimer's Disease (AD) within 3 years of memory loss
diagnosis of Mild Cognitive Impairment
age between 50-80 years
resident of San Diego or Orange Counties in California, or Ohio.
primary language English with no aphasia (no communication impairment)

Exclusion Criteria:

• seizure disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California - San Diego	San Diego	California	United States	92093-0626
2	Case Western Reserve University	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

Mark Tuszynski
Case Western Reserve University
Ohio State University

Investigators

Principal Investigator: Mark Tuszynski, M.D., Ph.D., University of California, San Diego

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Mark Tuszynski, Professor, University of California, San Diego

ClinicalTrials.gov Identifier:

NCT05040217

Other Study ID Numbers:

UCSD-BDNF1

First Posted:

Sep 10, 2021

Last Update Posted:

Sep 10, 2021

Last Verified:

Sep 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Mark Tuszynski, Professor, University of California, San Diego

Mild Cognitive Impairment

Additional relevant MeSH terms:

Alzheimer Disease

Cognitive Dysfunction

Mitogens

Study Results

No Results Posted as of Sep 10, 2021