Safety Studies for Clinical Trials of a Botanical Drug for Sickle Cell Disease

DESCRIPTION provided by applicant New therapeutic agents are urgently needed for the treatment of sickle cell disease the worldandapos s most common genetic disease Our long term goal is to develop a botanical drug SCD for use in children and adults that slows or stops disease progression Sickle cell disease affects approximately people in the United States and millions worldwide In the US those with SCD have an average mortality in their s and an estimated aggregate cost of medical care in excess of $ billion per year In less developed countries of children with SCD die before the age of five The only FDA approved disease modifying drug for use in SCD is the anti cancer drug hydroxyurea which has serious side effects and is only approved for use in adults Sickle cell disease results from a mutation in the globin gene Hb S a variant of Hb A the common adult hemoglobin When deoxygenated Hb S polymerizes forming long polymers that deform the biconcave red blood cells RBCs into rigid adherent sickle shaped cells The rigid sickled RBCs are easily trapped in the microvasculature blocking blood flow to tissues and organs with resultant ischemic tissue damage Best supportive therapies for SCD include folic acid for anemia penicillin to prevent infections pneumococcal and influenza vaccinations pain medication and intravenous injection of fluids Chronic transfusion therapy can modify the course of the disease but hyperviscosity alloimmune reaction infection and iron overload are just a few of the complications of transfusion therapy Bone marrow transplants can cure SCD but the morbidity and mortality of the procedure coupled with difficulty in finding a donor match and the cost of the procedure leave this an uncommon treatment option SCD is being evaluated in a Phase B dose escalation trial in adults with sickle cell disease to obtain an initial safety profile and explore possible effective oral doses that inhibit RBCs from sickling Early data shows that SCD can inhibit RBC sickling in humans To proceed to a Phase II clinical trial additional non clinical studies are needed This Phase II grant proposal is for funding the necessary non clinical studies PUBLIC HEALTH RELEVANCE This proposal supports elucidation of the mechanism of action of a botanical drug to treat sickle cell disease Sickle cell disease is an inherited blood disorde that affects over persons in the U S Those affected often have high medical costs a poor quality of life and early death The development of this drug addresses a critical unmet medical to treat this disease