and a normal one
Image by Betty Pace
Preclinical research suggests a drug used to treat multiple myeloma (MM) might also prove effective in the treatment of sickle cell disease (SCD).
Researchers say this study is the first to reveal how the drug, pomalidomide, increases the production of fetal hemoglobin, which is known to interfere with the sickling of red blood cells.
“We knew the drug would make fetal hemoglobin, but we didn’t know to what extent or how,” said Lionel Blanc, PhD, of the Feinstein Institute for Medical Research in Manhasset, New York.
He and his colleagues reported their findings in Blood.
The researchers’ in vitro experiments revealed that pomalidomide reverses γ-globin silencing during adult erythropoiesis, and the drug delays the maturation of early erythroid precursors without impairing terminal differentiation.
The team also found that pomalidomide selectively targets BCL11A and SOX6 to induce γ-globin synthesis, the drug’s mechanism of action during erythropoiesis is independent of IKZF1 degradation, and pomalidomide partially reprograms adult erythroid progenitors to a fetal-like state.
Finally, the researchers discovered that pomalidomide’s mechanism of action is conserved in cells from SCD patients, and treatment with pomalidomide leads to γ-globin production in MM patients.
“We can also say something else—that hydroxyurea, the only FDA-approved drug for sickle cell anemia, was less effective than pomalidomide and appeared to act through a different mechanism of action,” Dr Blanc said.
“The current therapy is good, but not everyone responds equally to hydroxyurea, and what we hope with pomalidomide is to improve this.”
Dr Blanc and his colleagues plan to launch a clinical trial in the near future to test pomalidomide in young adults with SCD.
