# Supplemental Request:  Therapeutic APOE2 overexpression for early Alzheimer's disease

> **NIH NIH U01** · CHILDREN'S HOSP OF PHILADELPHIA · 2022 · $1,393,438

## Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by the
gradual appearance of progressive cognitive dysfunction with neuronal death in multiple areas
of the cerebral cortex. Current therapies are symptomatic and there are no available treatments
that alter the natural history of the disease. In previous proof-of-concept studies, and backed by
strong human genetics data, we demonstrated that a single injection of an adeno-associated
viral (AAV) vector into the lateral ventricle of AD mice leads to sustained APOE2 expression
from ependymal cells and secretion into the cerebrospinal fluid (CSF). Once in the CSF, this
protein distributes throughout the entire brain with a beneficial effect on many AD-related
phenotypes. Moreover, therapeutic levels of expression were also achieved using the same
approach in non-human primates.
Here, we propose to move our therapeutic vector through a milestone-driven process that ends
with an IND application for a Phase 1 clinical trial in human subjects. Specifically, we propose to
1) hold a Pre-IND Type B meeting with the CBER of the FDA to receive input on the design of
the planned GLP tox study and the proposed Phase 1 protocol; 2) produce GMP-process
comparable vector (GLP vector); 3) perform IND-enabling GLP pharm/tox studies in nonhuman
primates (Rhesus macaques); 4) generate GMP-grade vector; and 5) prepare and file the IND
with the FDA for a phase I/II clinical trial in subjects with early symptomatic AD.

## Key facts

- **NIH application ID:** 10596304
- **Project number:** 3U01NS111671-03S1
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Beverly L. Davidson
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,393,438
- **Award type:** 3
- **Project period:** 2019-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10596304

## Citation

> US National Institutes of Health, RePORTER application 10596304, Supplemental Request:  Therapeutic APOE2 overexpression for early Alzheimer's disease (3U01NS111671-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10596304. Licensed CC0.

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