# Targeting PGC-1a for the treatment of sickle cell disease

> **NIH NIH R01** · BOSTON MEDICAL CENTER · 2022 · $350,000

## Abstract

ABSTRACT
 Sickle cell disease (SCD) and -thalassemia are genetic disorders affecting the structure or production
of hemoglobin. They are growing global health burden afflicting millions around the world. Sufficient fetal
hemoglobin (HbF) induction can reduce morbidity and mortality in SCD. The same is true for -thalassemia. The
standard current therapy for HbF induction in SCD hydroxyurea (HU) which in adults, does not usually ameliorate
sufficiently either sickle vaso-occlusion or hemolysis. Therefore, the search for more effective and safer small
molecule HbF inducers is a key unmet need in the management of SCD. We recently discovered that the
peroxisome proliferator activated receptor gamma coactivator-1 (PGC-1) is involved in the regulation of the
globin genes. Upregulation of PGC-1α by lentivirus infection or by a small molecule compound ZLN005 in human
primary erythroid progenitor CD34+ cells induced HbF expression and increased the percent of F-cells without
affecting cell proliferation and differentiation. Activation of PGC-1α by ZLN005 might provide a new path into
hemoglobin regulation with a promising therapeutic benefit in SCD. We intend to test for in vivo therapeutic
effects of ZLN005 in sickle cell mice. The findings from these preclinical studies could provide initial proof of
principle for developing safer, more beneficial small molecule therapeutics for SCD treatment and lead to early-
phase clinical trials.

## Key facts

- **NIH application ID:** 10519653
- **Project number:** 1R01HL155451-01A1
- **Recipient organization:** BOSTON MEDICAL CENTER
- **Principal Investigator:** Shuaiying Cui
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $350,000
- **Award type:** 1
- **Project period:** 2022-07-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10519653

## Citation

> US National Institutes of Health, RePORTER application 10519653, Targeting PGC-1a for the treatment of sickle cell disease (1R01HL155451-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10519653. Licensed CC0.

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