Hematopoietic Stem‐Cell Gene Therapy for Cerebral Adrenoleukodystrophy

  title={Hematopoietic Stem‐Cell Gene Therapy for Cerebral Adrenoleukodystrophy},
  author={Florian S. Eichler and Christine N. Duncan and Patricia L. Musolino and Paul J. Orchard and Satiro De Oliveira and Adrian J. Thrasher and Myriam Armant and Colleen H Dansereau and Troy C. Lund and Weston P Miller and G.V. Raymond and Raman Sankar and Ami J. Shah and Caroline Sevin and Bobby H. Gaspar and Paul Gissen and Hernan M. Amartino and Drago Bratkovic and Nicholas Jc Smith and Asif M. Paker and Esther Shamir and Tara O'Meara and David Davidson and Patrick R. Aubourg and David A. Williams},
  journal={The New England Journal of Medicine},
BACKGROUND In X‐linked adrenoleukodystrophy, mutations in ABCD1 lead to loss of function of the ALD protein. Cerebral adrenoleukodystrophy is characterized by demyelination and neurodegeneration. Disease progression, which leads to loss of neurologic function and death, can be halted only with allogeneic hematopoietic stem‐cell transplantation. METHODS We enrolled boys with cerebral adrenoleukodystrophy in a single‐group, open‐label, phase 2–3 safety and efficacy study. Patients were required… 

Treatment of cerebral adrenoleukodystrophy: allogeneic transplantation and lentiviral gene therapy

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, to review the history and experience with HSCT in cerebral ALD.

The Landscape of Hematopoietic Stem Cell Transplant and Gene Therapy for X-Linked Adrenoleukodystrophy

Gene therapy and optimized hematopoietic stem cell transplant for childhood CALD have changed the natural history of this previously devastating neurological disease.

Successful donor engraftment and repair of the blood-brain barrier in cerebral adrenoleukodystrophy.

The data suggest that robust donor myeloid recovery is necessary for timely repair of the blood-brain barrier (BBB) disruption and an active inflammatory disease process inrenoleukodystrophy.

Neurometabolic disease: Gene therapy success for cerebral adrenoleukodystrophy

Lenti-D therapy appears to be poised as a real treatment option for cerebral adrenoleukodystrophy, and it might even become the first gene therapy approved by the FDA, according to a new study.

Survival and Functional Outcomes in Boys with Cerebral Adrenoleukodystrophy with and without Hematopoietic Stem Cell Transplantation.

  • G. RaymondP. Aubourg T. Lund
  • Medicine
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • 2019

Management of adrenoleukodystrophy: From pre-clinical studies to the development of new therapies.

  • C. MaCheng Li Q. Lian
  • Biology, Medicine
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
  • 2021

The experience of allogeneic hematopoietic stem cell transplantation in a patient with X-linked adrenoleukodystrophy.

Clinical efficacy of haematopoietic stem cell transplantation for adult adrenoleukodystrophy

Accumulated experience supports the efficacy of allogenic haematopoietic stem cell transplantation in arresting the progression of childhood-onset cerebral form of adrenoleukodystrophy in early stages and arrested the inflammatory demyelination in all the patients with adolescent-/adult-onsets cerebral form/cerebello-brainstem form of Adrenoleukodstrophy.

Hematopoietic Stem Cell Gene Therapy for Cystinosis: From Bench-to-Bedside

An autologous transplantation approach of HSPCs modified ex vivo using a self-inactivated lentiviral vector to introduce a functional version of the CTNS cDNA, pCCL-CTNS, and showed its efficacy in Ctns−/− mice is developed.



Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy

Lentiviral-mediated gene therapy of hematopoietic stem cells can provide clinical benefits in ALD, and progressive cerebral demyelination in the two patients stopped, a clinical outcome comparable to that achieved by allogeneic HCT.

Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy

The reconstitution of ARSA activity in the cerebrospinal fluid and the arrested progression of neurodegenerative disease in the three treated patients demonstrate that the transplanted cells, or their progeny, can seed the nervous system and deliver therapeutic levels of active enzyme.

Cerebral X-linked adrenoleukodystrophy: the international hematopoietic cell transplantation experience from 1982 to 1999.

It is concluded that boys with early-stage disease benefit from HCT, whereas boys with advanced disease may be candidates for experimental therapies.

Haematopoietic stem cell transplantation in 12 patients with cerebral X-linked adrenoleukodystrophy

It is confirmed that haematopoietic stem cell transplantation can stop the progress of demyelination when performed at a critical early stage of the disease.

Hematopoietic cell transplantation does not prevent myelopathy in X-linked adrenoleukodystrophy: a retrospective study

HCT for cerebral ALD in childhood does not prevent the onset of AMN in X-ALD in adulthood, and this retrospective study found that three out of five patients in this cohort who underwent HCT in childhood developed signs of myelopathy in adulthood.

Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy.

  • D. BeamM. Poe M. Escolar
  • Medicine, Biology
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • 2007

Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and Hurler syndrome.

Good outcomes were obtained when HSCT was performed before adulthood, early in the clinical course, and/or from a related donor for these disorders.

Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome

A clinical protocol based on lentiviral vector (LV) gene transfer into autologous hematopoietic stem/progenitor cells (HSCs) resulted in robust, stable, and long-term engraftment of gene-corrected HSCs in the patients’ bone marrow, and the findings support the use of LV gene therapy to treat patients with WAS.