Preclinical research suggests synthetic peptides called minihepcidins could potentially treat beta-thalassemia and polycythemia vera (PV).
Investigators found that minihepcidin helped to restore normal levels of red blood cells (RBCs) and reduced spleen enlargement in mouse models of beta-thalassemia and PV.
Minihepcidin also controlled the accumulation of excess iron in the mice.
“It seems counterintuitive that one compound could treat two diseases that are quite different, but by restricting iron absorption, it also helps to normalize red blood cell levels in animals,” said study author Stefano Rivella, PhD, of The Children’s Hospital of Philadelphia in Pennsylvania.
“If these preclinical results translate to humans, this could represent a new treatment for both disorders.”
Dr Rivella and his colleagues described the results in Blood.
The investigators used minihepcidins, modified versions of the naturally occurring hormone hepcidin, which regulates iron. Minihepcidins are smaller than the full-length hormone but have long-term stability and long-lasting biological activity when administered to animals.
Previous research showed that minihepcidin treatment can prevent iron overload in mouse models of hemochromatosis.
So Dr Rivella and his colleagues wanted to determine how minihepcidins affect beta-thalassemia and PV in mice separately engineered to model each disease.
The team found that, in young mice that modelled beta-thalassemia, minihepcidin treatment normalized RBC levels and relieved both anemia and iron overload.
In older mice, minihepcidin improved RBC production and did not interfere with a chelating drug used to remove excess iron deposits.
In mice expressing the orthologous JAK2 mutation causing human PV, minihepcidin normalized RBC production.
Because increased iron absorption in PV keeps RBC production in overdrive, when minihepcidin curtailed iron absorption, it lowered the abnormally high numbers of RBCs, which also reduced spleen enlargement.
Dr Rivella noted that if minihepcidins prove successful in clinical trials, they may provide an important tool in treating these blood disorders.
“In animals affected by beta-thalassemia, the compound blocks iron from getting into organs but doesn’t remove excess iron already in organs and tissues,” Dr Rivella said. “If minihepcidins are used in older patients, they would need to be combined with existing chelating drugs that remove the already-accumulated iron.”
However, he added that, in beta-thalassemia, providing minihepcidins in childhood might halt iron accumulation and prevent more severe adult disease.
In PV, minihepcidins may help normalize a patient’s RBC production but, as in beta-thalassemia, would not treat the underlying disease-causing mutations.
Merganser Biotech Inc. is developing minihepcidins as novel therapies for rare hematologic diseases. Merganser’s lead compound, M012, is now under evaluation in a phase 1 clinical program as a potential therapy for beta-thalassemia, low-risk myelodysplasia, PV, alpha-thalassemia, and sickle cell disease.
The company’s chief executive officer, Brian MacDonald, MB ChB, PhD, is a co-author of the current study. Dr Rivella is a paid consultant on Merganser Biotech’s clinical trial, owns restricted stocks in Merganser, and is a member of its scientific advisory board.
