Federal Project Grant Award Summary

The National Heart, Lung, and Blood Institute (NHLBI) awarded St. Jude Children's Research Hospital Inc. a Project Grant of $1,834,564 under the Cardiovascular Diseases Research program (CFDA 93.837), effective July 5, 2026, with completion scheduled for March 31, 2028. This award funds pre-clinical research to establish the scientific rationale for senescence-targeting therapies (STTs) to improve hematopoietic stem and progenitor cell (HSPC) function and mobilization in sickle cell disease (SCD) patients. The research builds on preliminary findings demonstrating that treatment with navitoclax (ABT-263), a senescence-targeting compound, reduced DNA damage in bone marrow HSPCs and restored hematopoietic repopulating activity in SCD mouse models. The project's primary deliverables include mechanistic research characterizing HSPC senescence pathways in SCD, validation of STT efficacy in pre-clinical models, and development of supporting evidence for clinical translation of these therapies to improve outcomes in hematopoietic cell transplantation and gene therapy applications.

The research addresses a critical clinical gap in SCD management, where chronic bone marrow inflammation and hematopoietic stress induce premature senescence and DNA damage in HSPCs, potentially increasing the risk of secondary hematologic malignancies when patients undergo cytotoxic chemotherapy or gene therapy—currently the only potentially curative treatment options for SCD. By establishing pre-clinical rationale for STT-based interventions, this project supports the scientific foundation necessary to advance these therapies toward clinical evaluation and ultimately improve treatment safety and efficacy for the estimated 100,000 SCD patients in the United States.