Potential therapeutic modalities of reawakening fetal hemoglobin simulated by reaction systems

Abstract

Thalassemia syndromes are a diverse group of inherited genetic disorders. There are different types of thalassemia disorders, such as, Β-thalassemia, which is also called Mediterranean anemia, that is an inherited disease that played a major role in the American thriller movie, “Dying of the light” starring Nicolas Cage (Dec. 2014). In this study, we focus on the beta-globin (Β-globin) gene family related disorders. We seek potential amelioration strategies for Β-thalassemia and sickle cell anemia via γ-globin gene induction. In this work, a simulation model is developed, utilizing a reaction systems methodology. These systems are finite and based on a discrete time scale and can be used to describe and analyze complex biological systems and biological phenomenon. In our model, simulations of normal and abnormal cases of fetal, to adult hemoglobin switching developmental stage are illustrated. Various types of known and potential treatment strategies for Β-thalassemia and sickle cell anemia cases from the literature have been utilized to validate our model, used for identifying new potential treatments to be tested by molecular biologists, in the future studies. Moreover, we propose a novel potential simulation, as a therapeutic means, for Β-thalassemia and sickle cell anemia, by identifying FOG1 as a potential target. Finally, our proposed model, based on a reaction systems methodology, shows that inhibition of FOG1 expression by using methods, such as, RNAi induces γ-globin gene expression and can compensate for the lack of beta-globin in patients suffering from Β-globin gene related diseases, such as, Β-thalassemia and sickle cell anemia.