The potential role of LSD1 inhibitors in the treatment of sickle cell disease: A review of preclinical animal model data.

The potential role of LSD1 inhibitors in the treatment of sickle cell disease: A review of preclinical animal model data. Am J Physiol Regul Integr Comp Physiol. 2018 Aug 01;: Authors: Rivers A, Jagadeeswaran R, Lavelle D Abstract Sickle cell disease (SCD) is caused by a mutation of the b-globin gene(21) that triggers the polymerization of deoxygenated sickle hemoglobin (HbS). Approximately 100,000 SCD patients in the U.S. and millions worldwide(53) suffer from chronic hemolytic anemia, painful crises, multisystem organ damage, and reduced life expectancy(60, 70). Hematopoietic stem cell (HSC) transplantation can be curative, but the majority of patients do not have a suitable donor (80). Advanced gene editing technologies also offer the possibility of a cure (16, 34), but the likelihood that these strategies can be mobilized to treat the large numbers of patients residing in developing countries is remote. A pharmacological treatment to increase HbF as a therapy for SCD has been a long sought goal because increased levels of Fetal Hemoglobin [(HbF(α2γ2)] inhibit the polymerization of HbS(56, 78) and are associated with reduced symptoms and an increased lifespan of SCD patients(54, 55). There are only two drugs FDA approved for sickle cell disease treatment, hydroxyurea (HU) and L-glutamine. HU is ineffective at Hb F induction in approximately 50% of patients(6). While polymerization of sickle hemoglobin (HbS) has been traditionall...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research