Gene Therapy in a Patient with Sickle Cell Disease: Brief Report
@article{Ribeil2017GeneTI, title={Gene Therapy in a Patient with Sickle Cell Disease: Brief Report}, author={Jean-Antoine Ribeil and Salima Hacein-Bey-Abina and Emmanuel Payen and Alessandra Magnani and Michaela Semeraro and Elisa Magrin and Laure Caccavelli and B{\'e}n{\'e}dicte Neven and Philippe Bourget and Wassim El Nemer and Pablo Bartolucci and Leslie Weber and Herv{\'e} Puy and Jean François Meritet and David Grevent and Yves Beuzard and Stany Chrétien and Thibaud Lef{\`e}bvre and R W Ross and Olivier N{\`e}gre and Gabor Istvan Veres and Laura Sandler and Sandeep Soni and Mariane de Montalembert and St{\'e}phane Blanche and Philippe Leboulch and Marina Cavazzana}, journal={The New England Journal of Medicine}, year={2017}, volume={376}, pages={848–855} }
Abstract Sickle cell disease results from a homozygous missense mutation in the β‐globin gene that causes polymerization of hemoglobin S. Gene therapy for patients with this disorder is complicated by the complex cellular abnormalities and challenges in achieving effective, persistent inhibition of polymerization of hemoglobin S. We describe our first patient treated with lentiviral vector–mediated addition of an antisickling β‐globin gene into autologous hematopoietic stem cells. Adverse…
Figures from this paper
328 Citations
Promise of gene therapy to treat sickle cell disease
- Medicine, BiologyExpert opinion on biological therapy
- 2018
This review focuses on techniques to treat SCA by ex vivo genetic manipulation of hematopoietic stem/progenitor cells (HSPC), emphasizing replacement gene therapy and gene editing.
Gene Therapy of the Hemoglobinopathies
- Medicine, BiologyHemaSphere
- 2020
The potential and the challenges of gene addition and gene editing strategies for the hemoglobin diseases are discussed and a relevant chance to this group of patients for whom cure has previously not been on the horizon is offered.
Treating sickle cell anemia
- Medicine, BiologyScience
- 2020
Research on sickle cell anemia has again taken center stage because of new drug therapies, cures through stem cell transplantation, and the promise of gene therapy.
Gene Therapy for Hemoglobinopathies
- Medicine, BiologyHuman gene therapy
- 2018
Gene-editing technology may provide a therapeutic alternative overcoming some of the limitations ofGene therapy for β-thalassemia and sickle-cell disease, though proving its safety and efficacy will most likely require extensive clinical investigation.
Hemoglobin disorders: lentiviral gene therapy in the starting blocks to enter clinical practice.
- MedicineExperimental hematology
- 2018
Are genetic approaches still needed to cure sickle cell disease?
- MedicineThe Journal of clinical investigation
- 2019
Allogeneic blood or marrow transplantation (alloBMT) is the only cure for patients with sickle cell disease (SCD), and it is concluded that this disease burden has a considerable impact on individuals affected and on health care systems.
Combination of lentiviral and genome editing technologies for the treatment of sickle cell disease.
- BiologyMolecular therapy : the journal of the American Society of Gene Therapy
- 2021
Pre-clinical Development of a Lentiviral Vector Expressing the Anti-sickling βAS3 Globin for Gene Therapy for Sickle Cell Disease
- Biology, MedicineMolecular therapy. Methods & clinical development
- 2018
Gene therapy of hemoglobinopathies: progress and future challenges.
- Biology, MedicineHuman molecular genetics
- 2019
The most recent clinical trials for β-thalassemia and SCD are showing promising outcomes: patients were able to discontinue transfusions or had reduced transfusion requirements, however, toxic myeloablation and the high cost of current ex vivo HSC gene therapy platforms represent a barrier to a widespread application of these approaches.
References
SHOWING 1-10 OF 37 REFERENCES
Correction of Sickle Cell Disease in Transgenic Mouse Models by Gene Therapy
- Biology, MedicineScience
- 2001
In two mouse SCD models, Berkeley and SAD, inhibition of red blood cell dehydration and sickling was achieved with correction of hematological parameters, splenomegaly, and prevention of the characteristic urine concentration defect.
Gene Therapy of the β-Hemoglobinopathies by Lentiviral Transfer of the βA(T87Q)-Globin Gene
- BiologyHuman gene therapy
- 2016
Proof-of-principle of efficacy and safety has already been obtained in multiple patients with β-thalassemia and sickle cell disease, and βAT87Q-globin is used both as a strong inhibitor of HbS polymerization and as a biomarker.
Outcomes of Gene Therapy for Severe Sickle Disease and Beta-Thalassemia Major Via Transplantation of Autologous Hematopoietic Stem Cells Transduced Ex Vivo with a Lentiviral Beta AT87Q-Globin Vector
- Medicine
- 2015
Gene therapy using autologous HSC transduced with LentiGlobin BB305 lentiviral vector is a promising approach for the treatment of patients with hemoglobinopathies.
Interim Results from a Phase 1/2 Clinical Study of Lentiglobin Gene Therapy for Severe Sickle Cell Disease
- Medicine
- 2016
The toxicity profile observed from start of conditioning to latest follow-up was consistent with myeloablative conditioning with single-agent busulfan, and there have been no DP-related ≥Grade 3 AEs or serious AEs, and no evidence of clonal dominance or RCL.
Hematopoietic cell transplantation for thalassemia and sickle cell disease: past, present and future
- MedicineBone Marrow Transplantation
- 2008
The pediatric experience of HCT for hemoglobinopathies is illustrated and how these results affect future therapeutic decisions in children who inherit these disorders is discussed.
LentiGlobin gene therapy for transfusion-dependent β-Thalassemia: Update from the northstar HGB-204 phase 1/2 clinical study
- Medicine
- 2017
The toxicity profile observed was typical of myeloablative conditioning with single agent busulfan, and there have been no ≥ Grade 3 DP-related AEs and no evidence of clonal dominance or RCL during a median follow-up of 14.4 months post-infusion.
CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells
- Biology, MedicineNature
- 2016
These preclinical studies outline a CRISPR-based methodology for targeting haematopoietic stem cells by homologous recombination at the HBB locus to advance the development of next-generation therapies for β-haemoglobinopathies.
CRISPR/Cas9-Mediated Correction of the Sickle Mutation in Human CD34+ cells.
- BiologyMolecular therapy : the journal of the American Society of Gene Therapy
- 2016
The results demonstrate correction of the sickle mutation in patient-derived CD34+ cells using CRISPR/Cas9 technology, leading to the production of wild-type hemoglobin.
Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome
- Biology, MedicineScience
- 2013
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.
Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia
- Biology, MedicineNature
- 2010
It is shown that, 33 months after lentiviral β-globin gene transfer, an adult patient with severe βE/β0-thalassaemia dependent on monthly transfusions since early childhood has become transfusion independent for the past 21 months.