Gene therapy for monogenic disorders of the bone marrow

  title={Gene therapy for monogenic disorders of the bone marrow},
  author={Sujal Ghosh and Adrian J. Thrasher and H Bobby Gaspar},
  journal={British Journal of Haematology},
Ex‐vivo gene transfer of autologous haematopoietic stem cells in patients with monogenic diseases of the bone marrow has emerged as a new therapeutic approach, mainly in patients lacking a suitable donor for transplant. The encouraging results of initial clinical trials of gene therapy for primary immunodeficiencies were tempered by the occurrence of genotoxicity in a number of patients. Over the last decade, safer viral vectors have been developed to overcome the risk of insertional… 

Gene Therapy for Primary Immunodeficiencies

Clinical trials for SCID-X1, Wiskott-Aldrich syndrome, and recently ADA-SCID showed sustained engraftment of gene-corrected cells, restored immune function, and general improvement of clinical condition, with a positive safety profile, so continuous monitoring will be important to confirm long-term safety and efficacy.

Gene Therapy with Hematopoietic Stem Cells: The Diseased Bone Marrow's Point of View.

The present mini-review shall briefly summarize characteristics of the bone marrow content of the different stem and precursor cells and the cells' relationship with the stroma and outline the possible consequences and challenges.

Current status of ex vivo gene therapy for hematological disorders: a review of clinical trials in Japan around the world

  • K. Tani
  • Medicine
    International Journal of Hematology
  • 2016
The history and current status of clinical trials of ex vivo gene therapy for hematological disorders are introduced and discussed and six gene therapies have been approved in a limited number of countries worldwide.

Semi-automated closed system manufacturing of lentivirus gene-modified haematopoietic stem cells for gene therapy

A novel program for semi-automated cell isolation and culture equipment is developed to permit complete benchtop generation of gene-modified CD34+ blood cell products for transplantation, which are capable of stable, polyclonal multilineage reconstitution with follow-up of more than 1 year.

Gene Editing of Hematopoietic Stem Cells: Hopes and Hurdles Toward Clinical Translation

The state of the art of ex vivo gene editing with programmable nucleases in human hematopoietic stem and progenitor cells (HSPCs) is reviewed and the potential advantages and the current challenges toward safe and effective clinical translation are highlighted.

Thalassemia 2016: Modern medicine battles an ancient disease

  • D. Rund
  • Medicine
    American journal of hematology
  • 2016
A number of the original medical milestones of thalassemia diagnosis and treatment are traced, as well as some of the most recent developments which may lead to innovative therapeutic modalities.

Review on Thalassemia

Recent research has mainly focused on studying thalassemia at the basic science level, which resulted in the identification of unknown mechanisms leading to anemia and enabling the development of novel therapies which helps to improve the treatment of, and possibly cure the disease.

CD40 ligand deficiency: treatment strategies and novel therapeutic perspectives

This review highlights that beyond B cell defects, patients’ susceptibility to opportunistic pathogens might be due to impaired T cell and innate immune responses and how better knowledge of CD40L function and regulation may result in the development of new treatments.

Targeted gene therapy into a safe harbor site in human hematopoietic progenitor cells

The results show the possibility to specifically integrate genes at the SH6 locus in CD34 + progenitor cells, although further improvements in the efficacy of the procedure are required before this approach could be used for the gene editing of hematopoietic stem cells in patients with hematopolietic diseases.

Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes.



Gene therapy of chronic granulomatous disease: the engraftment dilemma.

This review summarizes the data from clinical trials for chronic granulomatous disease (CGD) and provides some insights into treatment options that may lead to a successful application of gene therapy for CGD.

Gene therapy for immunodeficiency due to adenosine deaminase deficiency.

Gene therapy, combined with reduced-intensity conditioning, is a safe and effective treatment for SCID in patients with ADA deficiency and effective protection against infections and improvement in physical development made a normal lifestyle possible.

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.

Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy.

Ex vivo gene therapy with gamma(c) can safely correct the immune deficiency of patients with X-linked severe combined immunodeficiency and allow patients to have a normal life.

Faster T-cell development following gene therapy compared with haploidentical HSCT in the treatment of SCID-X1.

If data of safety are confirmed over the long term, gene therapy for SCID-X1 appears to be an equal, if not superior, alternative to haploidentical HSCT.

Targeted gene therapy and cell reprogramming in Fanconi anemia

The results demonstrate for the first time the feasibility of correcting the phenotype of a DNA repair deficiency syndrome using gene‐targeting and cell reprogramming strategies.

Efficacy of gene therapy for X-linked severe combined immunodeficiency.

After nearly 10 years of follow-up, gene therapy was shown to have corrected the immunodeficiency associated with SCID-X1 and may be an option for patients who do not have an HLA-identical donor for hematopoietic stem-cell transplantation and for whom the risks are deemed acceptable.

Stem Cell Collection and Gene Transfer in Fanconi Anemia.

It is reported that FA patients have significant depletion of their BMCD34+ cell compartment even before severe pancytopenia is present, and oncoretroviral-mediated ex vivo gene transfer was efficient in clinical scale in FA-A cells, leading to reversal of the cellular phenotype in a significant percentage of CD34+ cells.

Lentiviral hematopoietic cell gene therapy for X-linked adrenoleukodystrophy.

Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1

The results suggest that gene therapy in combination with bone marrow conditioning can be successfully used to treat inherited diseases affecting the myeloid compartment such as CGD.