Gene therapy in a patient with sickle cell disease
Open accessAbstract
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 events were consistent with busulfan conditioning. Fifteen months after treatment, the level of therapeutic antisickling β-globin remained high (approximately 50% of β-like-globin chains) without recurrence of sickle crises and with correction of the biologic hallmarks of the disease. (Funded by Bluebird Bio and others; HGB-205 ClinicalTrials.gov number, NCT02151526 .).
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Betibeglogene autotemcel is approved in the EU for TDT with non-β0 mutations and no matched sibling donor, and is under study in β0/β0 TDT and SCD.
“Betibeglogene autotemcel, a lentiviral vector-based gene-addition product, is approved in the European Union for the treatment of patients with TDT who have non-β 0 mutations and who do not have a matched sibling donor 14 and is being studied in patients with β 0 /β 0 TDT genotypes and in those with SCD.15,16”
From CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia (2021) · cites this paper as [16]
The Discussion reports ongoing studies of the BB305 vector in patients with sickle cell disease and β-thalassemia. It also identifies four recipients as having transfusion-dependent β-thalassemia, but does not specify a β0/β0 genotype. The EU approval statement is attached to a different citation in the citing sentence and is not judged here. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn a patient with sickle cell anemia treated with the HbA T87Q-lentiviral approach, about 1 copy of the vector was present per cell; after 15 months, total hemoglobin was 11 to 12 g/dL, HbA T87Q formed about half of total hemoglobin, and the patient was asymptomatic.
“This same approach was used in a patient with sickle cell anemia.About 1 copy of this vector was present in each cell.After 15 months, total hemoglobin level was 11 to 12 g/dL; HbA T87Q formed about half of the total hemoglobin; and the patient was asymptomatic.117”
From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [117]
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- Authors
- Ribeil, J.-A., Hacein-Bey-Abina, S., Payen, E., Magnani, A., Semeraro, M., Magrin, E., Caccavelli, L., Neven, B., Bourget, P., El Nemer, W., Bartolucci, P., Weber, L., Puy, H., Meritet, J.-F., Grevent, D., Beuzard, Y., Chrétien, S., Lefebvre, T., Ross, R. W., Negre, O., Veres, G., Sandler, L., Soni, S., de Montalembert, M., Blanche, S., Leboulch, P., & Cavazzana, M.
- Affiliations
- Hôpital Necker-Enfants Malades (FR)
- Université Paris-Sud (FR)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-03-02
- Volume
- 376
- Issue
- 9
- Pages
- 848-855
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2593923181
- Semantic Scholar
- 34e8ed56e9412ab8396ea59eec8321aa12566c5b
- Cited by
- 696
- References
- 27
- Citations by year
- 2026: 24 · 2025: 40 · 2024: 42 · 2023: 62 · 2022: 71 · 2021: 99 · 2020: 108 · 2019: 99 · 2018: 95 · 2017: 52 · 2016: 2 · 2013: 1
- FWCI
- 64.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- bluebird bio
- Agence Nationale de la Recherche (ANR-11-LABX-0051)
- Université Paris Diderot
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- sickle cell disease, gene therapy, lentiviral vectors, autologous hematopoietic stem cells, beta-globin gene mutations, hemoglobin S polymerization, busulfan conditioning
- MeSH terms
- Adolescent, Anemia, Sickle Cell, Clinical Trials as Topic, Genetic Vectors, Hemoglobin A, Humans, Male, Genetic Therapy, Gene Expression, Lentivirus, beta-Globins
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