Gene therapy for other inherited blood disorders

Over 350,000 children are born each year with a severe inherited hemoglobin disorder, which accounts for 3.4 per cent of deaths in children below five years of age. Several gene therapy products are approved by regulatory authorities for other genetic diseases and complex disorders.

“Gene therapy should be considered as a conventional treatment for other blood disorders [besides hemophilia],” said Marina Cavazzana-Calvo, MD, Professor of Hematology at the Paris Descartes University, France. People with hematopoietic diseases benefit from the transplantation of hematopoietic stem cells from a healthy subject, but only 30 per cent have a human leukocyte antigen (HLA) identical donor. The use of autologous gene-modified cells can replace a missing acceptable hematopoietic stem cell donor and bypass immune issues that limit the use of HLA partially matched donors. Immune issues include rejection, graft-versus-host disease and length of immunological reconstitution.

Issues surrounding gene therapy include safety—specificity of “diseased” bone marrow—and expansion/transduction conditions. “A successful outcome will require appropriate management of patients before stem cell collection, appropriate dosing and choice of conditioning regimen, correct evaluation of the stem cell compartment, especially with respect to inflammation and infusion of an optimized graft.

Cavazzana-Calvo also discussed promising results being generated in trials of gene therapy in people with X-linked combined severe immune deficiency as well as those with thalassemia major or sickle cell disease. Future research is needed to address unanswered questions, such as whether gene therapy will offer a better quality of life to inherited bleeding disorders other than hemophilia.

Mitch Semienchuk, Editor, Hemophilia World Online, wishes to thank Georghia Michael. PhD, for her contributions to this article.