Identification of the Antisickling Compounds in SCD

ABSTRACT Sickle cell disease SCD affects approximately people in the United States and millions worldwide Symptoms appear shortly after birth and in less developed countries the majority of children with SCD die before the age of five In the U S SCD patients suffer chronic pain and fatigue severe acute painful crises requiring hospitalization and opiates strokes and multi organ damage and have an average mortality in their s The only FDA approved drug for adults with SCD is the anticancer drug hydroxyurea New treatments are desperately needed for both children and adults with SCD SCD is a botanical drug that inhibits red blood cell sickling in vitro and in vivo The formation of sickle shaped red blood cells caused by the polymerization of deoxygenated sickle hemoglobin is the primary and causative event in the molecular pathogenesis of sickle cell disease therefore inhibition of sickling by SCD should ameliorate the signs symptoms and slow the progression of sickle cell disease In a Phase B study SCD was shown to be safe and reduced pain and fatigue the two most common symptoms of sickle cell disease The compounds in SCD responsible for the antisickling activity are unknown as is the mechanism of antisickling Identification of the antisickling compounds would assist in clinical development and may enable the development of a more potent and effective drug for the treatment of sickle cell disease Identification of the antisickling compounds would assist in the elucidation of the mechanism by which SCD inhibits red blood cell sickling and point the way to a new target for antisickling drugs and the development of a new class of compounds to treat sickle cell disease Project Narrative About Americans have Sickle Cell Disease Those affected often have high medical costs a poor quality of life and early death Treatment options are few There is a substantial unmet medical need for new safe and effective disease modifying drugs like the one in this grant to treat this disease