The project relates to Sickle Cell Anemia (SCA), is a genetic disease and one of the most common severe disorders worldwide. The disease is due to a single change in the gene for the oxygen-carrying molecule hemoglobin in red blood cells, which results in the production of faulty hemoglobin and red blood cell deformation resulting in sickling. This in turn results are painful crises where patients experience acute episodes of pain. If left untreated, SCA leads to multiple organ damage and early mortality. SCA is a global health problem, as recognized by the World Health Organization (WHO) in 2008, the United Nations (UN) and the American Society of Hematology (ASH) in 2016. To date, around 300,000 newborns are affected yearly by the disease, and this number is expected to rise to 400,000 by 2050 . The vast majority of affected births occurs in Africa and the Indian subcontinent due to the selection of ickle mutation carriers through their survival advantage in malaria endemic regions. However, due to population movements, SCA has spread worldwide. Recent studies estimate that the overall number of births affected by SCA between 2010 and 2050 to be 14,242,000, with approximately 88% of those in sub-Saharan Africa. Due to a lack of early diagnosis and effective treatments in these countries, 50-90% of the newborns do not survive past the age of 5. Even in developed countries with the best medical care, life expectancy for SCD patients is reduced by about 30 years. Treatment options for SCA remain limited. Bone marrow transplantation and gene therapy offer the only curative approaches, albeit at considerable expense and carrying significant risks associated with transplantation and gene transfer. Blood transfusion is commonly used to treat SCD but has limited efficacy and serious side effects, including iron overload. Regardless of the associated risks or side effects, there are no resources for introducing these treatments in the parts of the world where they are most needed. Whereas several drugs are in the pipeline for development, to-date only one drug (hydroxycarbamide) remains the only widely used drug in the clinic to treat SCA. Therefore, there remains a pressing need to develop new drug-based treatments for SCD that are accessible to patients globally. To achieve this latter objective, the present project focused on understanding the basis for anemia in SCA. It is expected that the new knowledge obtained through these studies will help develop novel, effective and safe therapies that will be accessible in the parts of the world where they are most needed.
