# Neural Stem Cell Transplantation: A Novel Cellular Therapy for Alzheimer's Disease

> **NIH NIH U01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $1,371,564

## Abstract

Program Summary/Abstract
This U01 proposal is designed to provide the preclinical framework required to advance a novel stem cell
therapy to human clinical trials as an effective treatment for Alzheimer's disease (AD). AD is the most prevalent
age-related neurodegenerative disorder and leading cause of dementia, affecting an estimated 5.3 million
people in the U.S. There is no cure and no means of prevention. To date, a handful of traditional, single-target
pharmacological approaches have produced only marginal clinical improvements - there is a critical need for
more effective therapies. Therefore, the long-term goal of our research is to develop a disease-modifying
cellular therapy for AD that will have a meaningful impact on patients' lives. Cellular therapies target multiple
disease mechanisms and provide a multifaceted approach to treat the complex pathologies associated with
AD. In collaboration with Neuralstem, Inc., we have developed a unique line of human cortex-derived neural
stem cells (NSCs) that produce several neuroprotective growth factors. Our findings to date, as well as proof-
of- concept studies by others, show the benefit of cell therapies in AD models and indicate that efficacy is
enhanced when coupled with delivery of trophic factors. In our proposed approach, NSC transplantation will
combine the multifactorial therapeutic potential of a cellular therapy with sustained and directed delivery of
neurotrophic factors, providing increased benefit compared to traditional approaches and improving outcomes
in AD. Our preliminary data in a mouse model demonstrate that NSC transplantation is safe and effective,
significantly impacting cognition and reducing Aβ plaque burden. In this proposal, we will determine the
maximum tolerated dose and assess NSC bio-distribution and tissue tropism in two well-established and highly
relevant mouse models: 5XFAD and rTg4510. We will then perform large-scale efficacy testing of NSCs in
these mouse models and complete a dose-response feasibility study in non-human primates, which are
anatomically and cognitively more relevant to human clinical testing. Overall, our proposal will have a
significant impact on AD by providing proof-of-concept efficacy data for a well-characterized cellular therapy in
two relevant mouse models and safety data in a large animal with a brain structure that is more analogous to
humans. Completion of our proposed IND-enabling studies, as well as our laboratory's unique track record of
translating proof-of-principle animal studies to human trials, will enable this stem cell therapy to progress into
an attainable disease-modifying intervention for AD patients.

## Key facts

- **NIH application ID:** 9983530
- **Project number:** 5U01AG057562-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Eva Lucille Feldman
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,371,564
- **Award type:** 5
- **Project period:** 2018-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983530

## Citation

> US National Institutes of Health, RePORTER application 9983530, Neural Stem Cell Transplantation: A Novel Cellular Therapy for Alzheimer's Disease (5U01AG057562-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983530. Licensed CC0.

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