Gene therapy for thalassemia normalizes hemoglobin

Lentiviral vector hematopoietic stem cell (HSC) gene therapy represents a promising alternative to matched-sibling donor HSC transplants for treatment of beta thalassemia, with studies to date showing a safety profile that surpasses transplants from unrelated or alternative donors.

The prospect of a curative treatment raised by the work of Dr. Thompson and her colleagues also shows the feasibility of transfusion independence for beta⁰/beta^E patients, who carry the most common beta thalassemia genotype, and a significant reduction in transfusions even for patients with the more severe beta⁰/beta⁰ genotype.

Beta thalassemia has greatest prevalence in North Africa, the Middle East, and Asia, where access to treatments is limited and patients’ prognoses are often grim. Gene therapy for beta thalassemia could thereby represent the first large-scale implementation of this intervention in developing countries.

Bringing HSC gene therapy to more patients will require not just the availability of autologous HSCs, but of high-quality vector and reliable, high-volume manufacturing of transduced cells.

Harnessing this still-evolving technology to bring a potentially curative treatment to patients in developing countries is an exciting, but challenging, frontier for physicians and researchers involved with gene therapy.

Alessandra Biffi, MD, is director of the gene therapy program at Dana Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center, Boston. She serves on the board of directors of the American Society of Gene and Cell Therapy. These remarks were adapted from an accompanying editorial ( N Engl J Med. 2018;378[16]:1551-2 ).