Hematopoietic Stem Cell Transplantation and Hematopoietic Stem Cell Gene Therapy in X‐Linked Adrenoleukodystrophy

  title={Hematopoietic Stem Cell Transplantation and Hematopoietic Stem Cell Gene Therapy in X‐Linked Adrenoleukodystrophy},
  author={Nathalie Cartier and Patrick R. Aubourg},
  journal={Brain Pathology},
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only therapeutic approach that can arrest cerebral demyelination of X‐linked adrenoleukodystrophy (ALD) in boys and results in long‐term in a good quality of life, provided the procedure is performed at an early stage of disease. Similar benefits of allogeneic HSCT have been demonstrated in adults with cerebral ALD. However, it is not yet known whether allogeneic HSCT can prevent or rescue adrenomyeloneuropathy. Allogeneic HSCT… 

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.

Hematopoietic Stem Cell Transplantation for Neurological Disorders: A Focus on Inborn Errors of Metabolism

This review focuses on the mechanisms of brain repair resulting from HSCT and gene therapy in Inborn Errors of Metabolism, a large spectrum of multisystem disorders characterized by congenital deficiencies in enzymes involved in metabolic pathways.

Hematopoietic stem and progenitors cells gene editing: Beyond blood disorders

The most recent advances in hematopoietic stem and progenitor cell gene editing will be reported, with a focus on how this approach could be a promising solution to treat non-blood-related inherited disorders and the mechanisms behind the therapeutic actions discussed.

Current and Future Pharmacological Treatment Strategies in X‐Linked Adrenoleukodystrophy

Current and urgently needed future pharmacological therapies including the use of Lorenzo's oil and the inefficacy of lovastatin to normalize very‐long‐chain fatty acids in clinical trials as well as currently experimental and therefore possible future therapeutic strategies are reviewed.

Therapeutic Strategies for X-Linked Adrenoleukodystrophy, a Representative Peroxisomal Disorder

  • M. Morita
  • Medicine, Biology
    Peroxisomes: Biogenesis, Function, and Role in Human Disease
  • 2019
The necessity for newborn screening and the identification of predictive biological markers in X-ALD is described, and the current state of HSCT and pharmacological treatments are focused on.

Evaluation of Retinoids for Induction of the Redundant Gene ABCD2 as an Alternative Treatment Option in X-Linked Adrenoleukodystrophy

Investigation of the capacity of selected retinoids for ABCD2 induction in human monocytes/macrophages suggests a change in promoter accessibility during macrophage differentiation allowing induction ofABCD2 by retinoid.

Bone marrow transplantation into Abcd1‐deficient mice: Distribution of donor derived‐cells and biological characterization of the brain of the recipient mice

X‐linked adrenoleukodystrophy (X‐ALD) is a severe inherited metabolic disease with cerebral inflammatory demyelination and abnormal accumulation of very long chain fatty acid (VLCFA) in tissues,

[Hematopoietic stem cell transplantation in 2012: who? Where? How?].

  • J. Dalle
  • Medicine
    Archives de pediatrie : organe officiel de la Societe francaise de pediatrie
  • 2013

Recent Advances in Hematopoietic Stem Cell Gene Therapy

Although allergenic HSCT is also used to treat hereditary diseases, its indica‐ tions are restricted because of critical complications including regimen-related toxicities in‐ volving conditioning, infection, and graft-versus-host disease.

Superior long-term repopulating capacity of G-CSF+plerixafor-mobilized blood: implications for stem cell gene therapy by studies in the Hbb(th-3) mouse model.

The higher HSC yields, the faster hematological recovery, and the superiority in long-term engraftment indicate G-CSF+plerixafor-mobilized blood as an optimal graft source, not only for thalassemia gene therapy, but also for stem cell gene therapy applications in general.



Treatment of X‐linked childhood cerebral adrenoleukodystrophy by the use of an allogeneic stem cell transplantation with reduced intensity conditioning regimen

Non‐myeloablative HSCT should be considered as an early treatment for X‐ALD, a rapidly progressive demyelinating condition affecting the cerebral white matter, which rapidly leads to total disability and death.

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.

Matched Unrelated Human Umbilical Cord Blood Transplantation for X‐Linked Adrenoleukodystrophy

Unrelated cord blood transplantation may provide a good source of stem cells for patients with ALD when a matched sibling is not available.

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

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.

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.

Transduced CD34+ cells from adrenoleukodystrophy patients with HIV-derived vector mediate long-term engraftment of NOD/SCID mice.

Successful allogeneic unrelated bone marrow transplantation using reduced‐intensity conditioning for the treatment of X‐linked adrenoleukodystrophy in a one‐yr‐old boy

A one‐yr‐old boy with ALD who received HLA‐matched unrelated BMT in an early stage of the disease after careful planning and observation since his birth has been shown that BMT should be considered when a child has a biochemical diagnosis and MRI findings of ALD without any neurological signs.

Unrelated Allogeneic Bone Marrow Transplant in Adrenoleukodystrophy Using CD34+ Stem Cell Selection

A case where the authors used CD34+ stem cell selection for allogeneic unrelated-donor BMT in a patient with adrenoleukodystrophy is reported here.