Some sickle and some normal red blood cells: Wikipedia image

Gene Additive Therapy Prevents Pain Crisis Episodes in Sickle Cell Patients Interview with:

Markus Y Mapara, MD Professor of Medicine Director of the Blood and Marrow Transplantation Columbia University Medical Center

Dr. Mapara

Markus Y Mapara, MD
Professor of Medicine
Director of the Blood and Marrow Transplantation
Columbia University Medical Center What is the background for this study? What are the main findings? 

Response: Sickle cell disease is caused by a point mutation in the beta-globin gene of hemoglobin  resulting in the production of abnormal hemoglobin which leads to formation of sickle-shaped RBC under conditions of low oxygen. Sickle cell disease affects about 100,000 patients in the US which are predominantly African  American. The only curative approach is to perform an allogeneic bone marrow transplant which is however fraught with significant treatment-related risks if a matched sibling donor is not available.

The current study describes the successful application of a novel gene therapy  to treat patients with sickle cell disease. The strategy is based on a gene-addition approach to introduce the genetic information for a Hemoglobin F-like molecule termed HgAT87Q into hematopoietic stem cells. The expression of this novel  hemoglobin prevents polymerization of HgbS  and has now been demonstrated to prevent the occurrence of vaso-occlusive pain crises in sickle cell disease patients. How much does the therapy cost?

Response: At this point this is still investigational and there is therefore no price. What recommendations do you have for future research as a result of this work?

Response: The next big step is to achieve engraftment of genetically engineered stem cells without the need for the patient to undergo conditioning treatment in the form of high dose chemotherapy which is quite toxic. New approaches for non-myeloablative conditioning using antibody-mediated conditioning are currently under investigation in early trials and may further help to make this treatment safe and available to more patients.


Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease Gene Therapy

Julie Kanter, M.D., Mark C. Walters, M.D., Lakshmanan Krishnamurti, M.D., Markus Y. Mapara, M.D., Ph.D., Janet L. Kwiatkowski, M.D., M.S.C.E., Stacey Rifkin-Zenenberg, D.O., Banu Aygun, M.D., Kimberly A. Kasow, D.O., Francis J. Pierciey, Jr., M.Sc., Melissa Bonner, Ph.D., Alex Miller, B.Sc., Xinyan Zhang, Ph.D., December 12, 2021
DOI: 10.1056/NEJMoa2117175 is not a forum for the exchange of personal medical information, advice or the promotion of self-destructive behavior (e.g., eating disorders, suicide). While you may freely discuss your troubles, you should not look to the Website for information or advice on such topics. Instead, we recommend that you talk in person with a trusted medical professional.

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Last Updated on December 16, 2021 by Marie Benz MD FAAD