The Story of Beta-thalassemia: Blood, the Sea, and a Bluebird

Shawna-StanwoodBy Shawna Stanwood, PhD Student in Jefferies Lab



International Thalassemia Day took place on May 8th, and this year’s theme was “Access to Safe & Effective Drugs in Thalassaemia.”1 Dedicating a day in the calendar for thalassemia is well-justified. According to the World Health Organization (WHO), “the alpha and beta thalassaemias are the most common inherited single-gene disorders in the world with the highest prevalence in areas where malaria was or still is endemic.”2

Originating from “thalassa” and “haema,” the Greek words for sea and blood respectively,3 thalassemia is a hemoglobin disorder.4 Beta-thalassemia refers to thalassemia with decreased or absent beta-globin production, a component of hemoglobin.5

Beta-thalassemia minor, or beta-thalassemia trait, either does not manifest any symptoms or may result in mild anemia.6 Beta-thalassemia intermedia may produce a range of challenging symptoms, such as gallstones, jaundice, and leg ulcers.6 Consistent blood transfusions are usually needed for patients with the most severe of the beta-thalassemias, beta-thalassemia major.6

 According to the National Institutes of Health (NIH), blood transfusions, iron chelation therapy, folic acid supplementation, and stem cell transplantation can be used to treat thalassemia.7

Dr. Nick Au, a clinical assistant professor in the Department of Pathology and Laboratory Medicine, says that currently, only stem cell transplantation can be curative. He elaborates that the stem cells are usually obtained from a patient’s sibling who is immunologically similar, which reduces the morbidity related to the procedure.

“However, not all patients have an acceptable sibling donor. Also, even stem cell transplantation with fully matched siblings carries risk, including transplant associated mortality,” adds Dr. Au, who collaborates with Dr. Ross MacGillivray (Centre for Blood Research) and works at BC Children’s and Women’s Health Centre.

Nick Leschly CEO Bluebird Bio, Inc.

Nick Leschly
CEO Bluebird Bio, Inc.

Recently, a potential treatment option for beta-thalassemia major in the form of gene therapy has attracted much attention. In early 2015, a press release revealed that a drug product called LentiGlobin® BB305 by a company called Bluebird Bio, Inc. had been deemed a Breakthrough Therapy by the United States Food and Drug Administration.8 

This press release stated that “LentiGlobin BB305 Drug Product aims to treat beta-thalassemia major and severe sickle cell disease by inserting a functional human beta-globin gene into the patient’s own hematopoietic stem cells ex vivo and then returning those modified cells to the patient through an autologous stem cell transplantation.”8

However, even though gene therapy has made a big splash, the story is still not entirely complete. Dr. Au points out that “the long term efficacy and side effects of the current gene therapies still need to be determined.”

Looking toward the future, he anticipates that “although recent therapies show some promise, the ultimate goal of developing a permanent cure that offers a better risk profile than stem cell transplantation and that is predicted to work in all patients likely still requires more research and work.”