Defining curative endpoints for transfusion‐dependent β‐thalassemia in the era of gene therapy and gene editing

Abstract

Abstractβ‐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.

Editorial: Recent advances in pediatric red blood cells disorders

“…In future, implementations of the genetic screening will be crucial in order to detect genetic variants and possibly improve our capacity to correlate patients' phenotypes and genotypes ( 6 ). Moreover, advances in genetic technologies are not only useful to establish an accurate diagnosis, but also paved the way for potentially curative interventions for hemoglobinopathies ( 7 , 8 ). Recently, the Food and Drug Administration (FDA) approval of the first gene-editing based therapies for Sickle Cell Disease (SCD) marked a significant milestone in this field ( 9 ).…”