PGC-1α agonism induces fetal hemoglobin and exerts antisickling effects in sickle cell disease.
Sci Adv
; 10(31): eadn8750, 2024 Aug 02.
Article
em 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
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hemoglobina Fetal
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Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
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Anemia Falciforme
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Antidrepanocíticos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Estados Unidos