Zynteglo

Zynteglo (trade name, INN autologous CD34+ cells encoding βA-T87Q-globin gene, formerly known as LentiGlobin BB305) is a treatment for beta thalassemia, a rare and potentially debilitating blood disorder. It has been developed by bluebird bio and was given “breakthrough therapy” designation by the Food and Drug Administration in February, 2015.[1][2] It was approved by EMA in 2019.[3]

Mechanism of action

Beta thalassemia is caused by mutations to or deletions of the HBB gene leading to reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals.[4] LentiGlobin BB305 is a lentiviral vector which inserts a functioning version of the HBB gene into a patient's blood-producing hematopoietic stem cells (HSC) ex vivo. The resulting engineered HSC cells are then reintroduced to the patient.[5][6]

Development history

In early clinical trials several patients with beta thalassemia, who usually require frequent blood transfusions to treat their disease, were able to forgo blood transfusions for extended periods of time.[7][8][9] In 2018, results from phase 1-2 trials suggested that of 22 patients receiving Lentiglobin gene therapy, 15 were able to stop or reduce regular blood transfusions.[10][11]

See also

References
  1. "Ten things you might have missed Monday from the world of business". The Boston Globe. 3 February 2015. Retrieved 13 February 2015.
  2. "Lentiviral vectors". Monday, 8 July 2019
  3. "Zynteglo". European Medicines Agency. 25 March 2019. Retrieved 16 August 2019.
  4. Cao, Antonio; Galanello, Renzo (21 January 2010). "Beta-thalassemia". Genetics in Medicine. 12 (2): 61–76. doi:10.1097/GIM.0b013e3181cd68ed. PMID 20098328.
  5. Negre O, et al. (2015). "Preclinical evaluation of efficacy and safety of an improved lentiviral vector for the treatment of β-thalassemia and sickle cell disease" (PDF). Current Gene Therapy. 15 (1): 64–81. doi:10.2174/1566523214666141127095336. PMC 4440358. PMID 25429463.
  6. Thompson A, et al. (2014). "Initial Results from the Northstar Study (HGB-204): A Phase 1/2 Study of Gene Therapy for β-Thalassemia Major Via Transplantation of Autologous Hematopoietic Stem Cells Transduced Ex Vivo with a Lentiviral βΑ-T87Q -Globin Vector (LentiGlobin BB305 Drug Product)". Blood. 124 (21): 549. doi:10.1182/blood.V124.21.549.549.
  7. Cavazzana-Calvo M, Payen E, Negre O, et al. (2010). "Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia". Nature. 467 (7313): 318–22. doi:10.1038/nature09328. PMC 3355472. PMID 20844535.
  8. Winslow, Ron (8 December 2015). "New Gene Therapy Shows Promise for Lethal Blood Disease". The Wall Street Journal. Retrieved 13 February 2015.
  9. (8 December 2014) bluebird bio Announces Data Demonstrating First Four Patients with β-Thalassemia Major Treated with LentiGlobin™ are Transfusion-Free Yahoo News, Retrieved 17 May 2015
  10. Thompson, Alexis (19 April 2018). "Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia". New England Journal of Medicine. 378 (16): 1479–1493. doi:10.1056/NEJMoa1705342. PMID 29669226.
  11. Stein, Rob (18 April 2018). "Gene Therapy For Inherited Blood Disorder Reduced Transfusions". NPR. Retrieved 4 March 2019.
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