PGC-1α agonism induces fetal hemoglobin and exerts antisickling effects in sickle cell disease.
Sci Adv
; 10(31): eadn8750, 2024 Aug 02.
Article
en En
| MEDLINE
| ID: mdl-39083598
ABSTRACT
Sickle cell disease is a growing health burden afflicting millions around the world. Clinical observation and laboratory studies have shown that the severity of sickle cell disease is ameliorated in individuals who have elevated levels of fetal hemoglobin. Additional pharmacologic agents to induce sufficient fetal hemoglobin to diminish clinical severity is an unmet medical need. We recently found that up-regulation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) can induce fetal hemoglobin synthesis in human primary erythroblasts. Here, we report that a small molecule, SR-18292, increases PGC-1α leading to enhanced fetal hemoglobin expression in human erythroid cells, ß-globin yeast artificial chromosome mice, and sickle cell disease mice. In SR-18292-treated sickle mice, sickled red blood cells are significantly reduced, and disease complications are alleviated. SR-18292, or agents in its class, could be a promising additional therapeutic for sickle cell disease.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hemoglobina Fetal
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Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma
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Anemia de Células Falciformes
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Antidrepanocíticos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Sci Adv
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos