An open-label pilot study of recombinant granulocyte-colony stimulating factor in Friedreich's ataxia

Nat Commun. 2022 Aug 9;13(1):4655. doi: 10.1038/s41467-022-31450-w.

Abstract

Friedreich's ataxia (FA) is an inherited progressive neurodegenerative disease for which there is no proven disease-modifying treatment. Here we perform an open-label, pilot study of recombinant human granulocyte-colony stimulating factor (G-CSF) administration in seven people with FA (EudraCT: 2017-003084-34); each participant receiving a single course of G-CSF (Lenograstim; 1.28 million units per kg per day for 5 days). The primary outcome is peripheral blood mononuclear cell frataxin levels over a 19-day period. The secondary outcomes include safety, haematopoietic stem cell (HSC) mobilisation, antioxidant levels and mitochondrial enzyme activity. The trial meets pre-specified endpoints. We show that administration of G-CSF to people with FA is safe. Mobilisation of HSCs in response to G-CSF is comparable to that of healthy individuals. Notably, sustained increases in cellular frataxin concentrations and raised PGC-1α and Nrf2 expression are detected. Our findings show potential for G-CSF therapy to have a clinical impact in people with FA.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Friedreich Ataxia* / drug therapy
  • Granulocyte Colony-Stimulating Factor* / adverse effects
  • Granulocytes / metabolism
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Pilot Projects
  • Recombinant Proteins* / adverse effects

Substances

  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor

Associated data

  • EudraCT/2017-003084-34