14 Scopus citations


Introduction: Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder with an incidence of 1 in 14–17,000 male births, caused by pathogenic variants within the ABCD1 gene. By adulthood, approximately 40% of the patients develop cerebral ALD, a severe, neuroinflammatory condition that is generally progressive and fatal without intervention. Areas covered: Historically, only allogeneic hematopoietic stem cell transplantation (HSCT) has been shown to halt progression of cerebral ALD, with superior outcomes obtained when HSCT is performed early in the disease process. More recently, a lentiviral-based gene therapy approach has been investigated as therapy for cerebral ALD as an alternative to allogeneic transplantation. A focused literature review was performed using the terms ‘hematopoietic stem cell transplantation,’ ‘gene therapy’ and ‘adrenoleukodystrophy’ to include relevant literature, especially comparing the experience with gene therapy and HSCT outcomes. We review the history and experience with HSCT in cerebral ALD and its limitations, as well as the information currently available in association with the gene therapy trials for cerebral ALD. Expert opinion: The data regarding this lentiviral-based gene therapy approach and its relative risks and benefits is still being evaluated. This information is explored in the context of the experience with allogeneic HSCT for cerebral ALD.

Original languageEnglish (US)
Pages (from-to)1151-1162
Number of pages12
JournalExpert opinion on biological therapy
Issue number9
StatePublished - 2022

Bibliographical note

Funding Information:
A Gupta was an investigator on the Bluebird Bio ALD gene therapy trials, as well as the Bluebird Bio gene therapy trial for sickle cell disease. P Orchard was the Principal Investigator of the Bluebird Bio gene therapy trials for adrenoleukodystrophy (102 and 104). There was clinical trial support for these studies, but there is no conflict of interest as determined by the University of Minnesota’s COI group. P Orchard also has contracting relationships with Imel, Neurogene, Orchard Therapeutics, Emerging Therapy Solutions and is on the data safety monitoring board for Ionis. These are not relevant to this submission. G Raymond has an ongoing consultant relationship with Bluebird Bio. He was at the University of Minnesota for some of the time that the Bluebird Bio gene therapy studies were enrolling. S Kemp has received unrestricted research grant support from Bluebird Bio and Swanbio Therapeutics separate from the submitted work; has received consulting fees from Poxel and Swanbio Therapeutics for scientific advising outside the submitted work; participates in advisory boards for ALD Connect (unpaid), the European Leukodystrophy Association (unpaid), Alex, The Leukodystrophy Charity (unpaid) and the United Leukodystrophy Foundations (unpaid). S McIvor received research support from Bluebird Bio for basic and translational research studies. R Pierpont receives research support from the National Institutes of Health’s National Center for Advancing Translational Sciences, grants KL2TR002492 and UL1TR002494, the University of Minnesota Department of Pediatrics, ALD Alliance and CFC International. T Lund was an investigator on the Bluebird Bio ALD gene therapy trials, and had basic and translational research support from Bluebird Bio. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.


  • cerebral adrenoleukodystrophy
  • hematopoietic stem cell transplant
  • lentiviral gene therapy
  • therapeutic options in cerebral ALD


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