# Pharmacological rejuvenation of human hematopoietic stem cells

> **NIH NIH R43** · MOGLING BIO INC · 2024 · $299,781

## Abstract

Abstract/Summary
The goal of this application is to further develop a first-in-class therapeutic regimen that attenuates
aging of human hematopoietic stem cells (HSCs). Aging of hematopoiesis in older adults often
manifests as aging-associated anemia, progressive reduction in the immune response, and/or
increased incidence of myeloid malignancy. These aging associated declines are in part attributed to
the aging of hematopoietic stem cells (HSCs) and hematopoietic system that sustain our life-long
production of quality red blood cells, immune cells and white blood cells. Previous studies have
established, mostly in murine models, that elevated Cdc42 activity and loss of cell polarity serve as
aging associated biomarkers for HSCs and targeting Cdc42 activity via a lead small molecule Cdc42-
activity specific inhibitor, CASIN, can dose-dependently suppress elevated Cdc42 activity and loss of
polarity of aged animals to functionally rejuvenate or attenuate aging of murine HSCs. CASIN thus has
the potential to be further developed towards clinical applications to benefit human aging. The central
hypothesis of this proposal is that targeting Cdc42 activity with the drug CASIN can restored Cdc42-
regulated polarity and rejuvenate aged human HSCs ex vivo, which will benefit bone marrow HSC
transplant patients. The proposed studies will develop the proof-of-principle of an intervention to
rejuvenate aged blood forming system and validate CASIN in rejuvenating aged human HSC epigenetic
clock and function at well-defined ex vivo conditions. The proposal will also test a clinically applicable
closed circuit HSC manipulation apparatus for CASIN ex vivo treatment in future commercialization of
this technology. Upon completion of the proposed studies, we expect our product will move closer to
FDA IND filing and clinical trials in preventing or treating aging related functional decline of human
blood system to benefit the lives of older adults.

## Key facts

- **NIH application ID:** 10811003
- **Project number:** 1R43HL172285-01
- **Recipient organization:** MOGLING BIO INC
- **Principal Investigator:** JAMES C MULLOY
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $299,781
- **Award type:** 1
- **Project period:** 2024-09-23 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811003

## Citation

> US National Institutes of Health, RePORTER application 10811003, Pharmacological rejuvenation of human hematopoietic stem cells (1R43HL172285-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10811003. Licensed CC0.

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