Final Report Summary - ERYTHROTHERAPY (DEFINING NEW DRUGS AND DRUG TARGETS FOR TREATMENT OF ANEMIA) NEW ANEMIA RESEARCH TOOLS AND THERAPIES BASED ON DECODING RED BLOOD CELLDEVELOPMENT AND DISEASETwo billion people suffer from red blood cell deficiency or anemia, a debilitating condition often caused by failure to produce red blood cells. Today there is no effective therapy for many types of anemia, including aplastic anemias such as Diamond-Blackfan anemia (DBA). In this project we developed fundamentally new concepts for treating anemic patients that today lack effective treatment. RESULT 1.DEFINEE THE MECHANISMS REGULATING RED BLOOD CELL FATE THROUGH DIRECT REPROGRAMMING. Through a reductionist approach my team identified 4 factors that are able to directly reprogram fibroblasts to erythroid cells. The results were published in Cell Reports in 2016My research group will now continue this work studying the mechanisms of direct erythroid reprogramming in order to understand essential molecular events involved in determining erythroid fate. Our system will further be used to model congenital anemia and opens a door for developing cell therapy-based anemia treatment. In addition, this approach reduces the need to perform developmental research on animals. RESULT 2.DISCOVERY OF NOVEL DRUG CANDIDATES FOR DIAMOND-BLACKFAN ANEMIA (DBA). DBA is a congenital hypoplastic anemia and no drugs are available to correct the underlying problem, leaving patients with severely reduced life quality and life expectancy. Based on successful screening results we identified a promising drug target as well as a group of promising drug candidates for DBA (unpublished findings). Our exclusive results represent the first step towards developing disease-specific drugs.
