NIPRISAN FOR TREATING PATIENTS WITH SICKLE CELL DISEASE

DESCRIPTION (provided by applicant): Sickle Cell Disease (SCD) is a hereditary blood disorder caused by an abnormal hemoglobin called sickle hemoglobin (Hb S). Although the Hb S of patients with SCD in the steady state can transport oxygen like normal hemoglobin, Hb S forms rigid fibers when the blood is exposed to hypoxia. The deoxy-Hb S fibers push the red blood cell membrane toward the outside, causing deformation of the cells to assume a sickle shape. Rigid sickled cells cannot pass through narrow capillaries and they occlude blood vessels, which may cause serious organ damage. Although the cause of SCD is well known and more than 200,000 drugs have been screened, hydroxyurea is the only drug that is currently available for the treatment of patients with SCD. One problem with hydroxyurea, however, is that it is not uniformly effective in all patients and some patients develop severe adverse effects. In an attempt to develop a new anti-sickling agent, Xechem, together with researchers at the Children's Hospital of Philadelphia, PA, proposes testing of a new phytopharmaceutical anti-sickling agent, NIPRISAN, for the treatment of patients with SCD. NIPRISAN is the extract of four kinds of plants in Africa and has been used in Nigeria for the treatment of SCD for a long time. However, since it was not studied scientifically and the remedies were prepared differently in different areas, the drug has never been used in other countries. Recently, the Nigerian government performed preliminary studies on NIPRISAN and showed that oral administration of NIPRISAN led to a significant reduction in the frequency of painful episodes. The effectiveness of NIPRISAN was also studied at the Sickle Ceil Disease Reference Laboratory at the Children's Hospital of Philadelphia, PA, using transgenic (tg) sickle mice that produce human HbS. The aim of this application is to prepare a novel, safe, standardized drug that will be uniformly effective in patients with SCD with minimum adverse effects. For this purpose, in the Phase 1 study, we will prepare a standardized optimal formulation of NIPRISAN that will be easily administered orally, has a consistent anti-sickling effect among different lots, and maintains the maximum activity during the shelf time. The development of an effective anti-sickling agent not only is beneficial to patients with SCD and their families, but also will reduce the financial burden on governments and healthcare systems.