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

Kevin C Kemp*, Anastasia Georgievskaya, Kelly M Hares, Juliana Redondo, Steven Bailey, Claire M Rice, Neil J Scolding, Chris Metcalfe, Alastair Wilkins*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

1 Citation (Scopus)
38 Downloads (Pure)

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 cells (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.
Original languageEnglish
Article number4655 (2022)
Number of pages8
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - 9 Aug 2022

Bibliographical note

Funding Information:
We thank Ataxia UK for their assistance with recruiting participants and the North Bristol NHS Trust Research and Innovation for hosting the trial. The authors thank the participants, their families and carers for their generous time and commitment to this study. We thank Nigel Noel and Paul Virgo, at The Department of Immunology and Immunogenetics, North Bristol NHS Trust (Southmead Hospital, Bristol, UK), for their assistance with flow cytometry data acquisition. The study was funded by Ataxia UK; the Friedreich’s Ataxia Research Alliance (FARA); The Burden Institute; the Elizabeth Blackwell Institute; the Wellcome Trust [204813/Z/16/Z - ISSF3].

Funding Information:
We thank Ataxia UK for their assistance with recruiting participants and the North Bristol NHS Trust Research and Innovation for hosting the trial. The authors thank the participants, their families and carers for their generous time and commitment to this study. We thank Nigel Noel and Paul Virgo, at The Department of Immunology and Immunogenetics, North Bristol NHS Trust (Southmead Hospital, Bristol, UK), for their assistance with flow cytometry data acquisition. The study was funded by Ataxia UK; the Friedreich’s Ataxia Research Alliance (FARA); The Burden Institute; the Elizabeth Blackwell Institute; the Wellcome Trust [204813/Z/16/Z - ISSF3].

Publisher Copyright:
© 2022, The Author(s).

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