European Hematology Association: Treating Sickle Cell Disease and Beta-Thalassemia with CRISPR/Cas9 Gene Editing

MADRID, June 23, 2017 /PRNewswire/ --

Sickle Cell Disease and Beta-thalassemia are two severe diseases that are caused by defects in the beta-globin protein in hemoglobin, present in red blood cells.  Patients born with Sickle Cell Disease and Beta-thalassemia do not have symptoms when they are first born because their red cells still contain a protective fetal gamma globin protein of fetal hemoglobin. The fetal gamma globin, and thus fetal hemoglobin, disappears approximately 6-12 weeks after birth, at which time the patients develop harmful symptoms.

     (Logo: http://mma.prnewswire.com/media/524821/EHA_Logo.jpg )

Research over the last 50 years has identified a subset of patients with Sickle Cell Disease and Beta-thalassemia who have no or only minimal symptoms. In these patients the protective fetal hemoglobin fails to disappear after birth and instead persists into adulthood and protects them from the severe symptoms of Sickle Cell Disease and Beta-thalassemia. Such patients are said to have "Hereditary Persistence of Fetal Hemoglobin," which occurs because of small changes to the DNA in the cell.

Our approach is to use our CRISPR/Cas9 gene editing tool to re-create the small changes to the DNA that cause "Hereditary Persistence of Fetal Hemoglobin" and lead to expression of the protective fetal hemoglobin to reduce symptoms in patients with Sickle Cell Disease and Beta-thalassemia.  In our study we show that we can efficiently re-create the small DNA changes in a highly specific manner with no off-target effects.  We also show that these DNA changes do indeed lead to the predicted high levels of fetal hemoglobin.  Furthermore we show that the CRISPR/Cas9 process and these DNA changes do not lead to any cellular defects in the cells. We have ongoing safety studies to further demonstrate the safety of our approach.  Taken together, these studies support our Clinical Trial Application in 2017, to start clinical trials in 2018.    

Presenter: Dr Bill Lundberg

Affiliation: Cambridge, MA, USA

Topic: RE-CREATING HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN (HPFH) WITH CRISPR/CAS9 TO TREAT SICKLE CELL DISEASE (SCD) AND BETA-THALASSEMIA
(BETA-THAL)

Abstract S147 will be presented by Bill Lundberg on Friday, June 23 15:45 - 17:00 in Hall A.

About the EHA Annual Congress
Hematology is a specialty that covers everything to do with blood: its origin in the bone marrow, diseases of blood and their treatments. The latest data on research and developments will be presented. The topics range from stem cell physiology and development, to leukemia, lymphoma, myeloma - diagnosis and treatment; red blood cells -, white blood cells- and platelet disorders; thrombosis and bleeding disorders.