Defining curative endpoints for transfusion-dependent β-thalassemia in the era of gene therapy and gene editing.
Journal
American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369
Informations de publication
Date de publication:
15 Dec 2023
15 Dec 2023
Historique:
revised:
16
10
2023
received:
23
06
2023
accepted:
06
11
2023
medline:
15
12
2023
pubmed:
15
12
2023
entrez:
15
12
2023
Statut:
aheadofprint
Résumé
β-thalassemia is a monogenic disease that results in varying degrees of anemia. In the most severe form, known as transfusion-dependent β-thalassemia (TDT), the clinical hallmarks are ineffective erythropoiesis and a requirement of regular, life-long red blood cell transfusions, with the development of secondary clinical complications such as iron overload, end-organ damage, and a risk of early mortality. With the exception of allogeneic hematopoietic cell transplantation, current treatments for TDT address disease symptoms and not the underlying cause of disease. Recently, a growing number of gene addition and gene editing-based treatments for patients with TDT with the potential to provide a one-time functional cure have entered clinical trials. A key challenge in the design and evaluation of these trials is selecting endpoints to evaluate if these novel genetic therapies have a curative versus an ameliorative effect. Here, we present an overview of the pathophysiology of TDT, review emerging gene addition or gene editing therapeutic approaches for TDT currently in clinical trials, and identify a series of endpoints that can quantify therapeutic effects, including a curative outcome.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Vertex Pharmaceuticals
Informations de copyright
© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
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