Benserazide as a potential novel fetal hemoglobin inducer: an observational study in non-carriers of hemoglobin disorders

Blood Cells Mol Dis. 2021 Mar;87:102511. doi: 10.1016/j.bcmd.2020.102511. Epub 2020 Nov 5.


Induction of fetal hemoglobin production with hydroxyurea is an effective strategy in sickle cell disease and beta thalassemias, but up to 20% of patients do not respond to or cannot tolerate it. Benserazide is used in the treatment of Parkinson's disease and was noticed to induce gamma globin in preclinical models. We hypothesized that chronic treatment with benserazide-containing medication may be associated with increase in HbF production and in circulating F-cells. Blood samples were collected from 50 subjects including 35 patients on benserazide for Parkinson's disease, 10 healthy controls, and 5 patients with sickle cell anemia as positive controls for high fetal hemoglobin. We found a strong correlation between HbF and circulating F-cells in the entire population, but we found no significant increase in HbF and F-cell percentage in patients taking benserazide up to 700 mg daily. No hematologic abnormalities attributable to benserazide use after up to 22 years were detected. Our data support long-term safety and tolerability of benserazide at doses ten times higher than used in preclinical models to induce fetal hemoglobin. Further clinical trials enrolling patients with sickle cell disease and thalassemia are warranted to provide insight into its efficacy to treat those populations.

Keywords: Fetal hemoglobin; Hydroxyurea; Sickle cell disease; Thalassemia.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia, Sickle Cell / blood
  • Anemia, Sickle Cell / drug therapy
  • Antiparkinson Agents / pharmacology*
  • Antiparkinson Agents / therapeutic use
  • Antisickling Agents / pharmacology
  • Antisickling Agents / therapeutic use
  • Benserazide / pharmacology*
  • Benserazide / therapeutic use
  • Cross-Sectional Studies
  • Female
  • Fetal Hemoglobin / analysis*
  • Humans
  • Hydroxyurea / pharmacology
  • Hydroxyurea / therapeutic use
  • Male
  • Middle Aged
  • Parkinson Disease / blood
  • Parkinson Disease / drug therapy*
  • Young Adult


  • Antiparkinson Agents
  • Antisickling Agents
  • Benserazide
  • Fetal Hemoglobin
  • Hydroxyurea