new therapies for sickle cell disease

Sickle cell disease (SCD) affects ∼90,000 Americans, and constitutes the cause of serious morbidities and mortality in millions of patients throughout the world.  Unfortunately, few SCD patients live past 45 years, and the annual costs for treating children and adults approaches $10,000 and $30,000, respectively.  Even with several new therapies recently available, the quality of life still steadily decreases and prospects for new therapies outside of bone marrow transplantation remain dim.

In an effort to find a more effective therapy for SCD, ErythroCure is developing drugs with a novel mode of action that stabilize the sickle cell membrane and thereby suppress the discharge of prothrombotic membrane-derived microparticles, the release of vasculature-activating free hemoglobin, and the consequent formation of embolisms within the microvasculature that are likely responsible for the vaso-occlusive events that cause SCD. 

Despite malaria's designation by the World Health Organization (WHO) as one of six consensus global health priorities, malaria still remains a major health problem, with ~200 million new infections/year, nearly 500,000 deaths/year, and almost half of the world's population at risk of contracting the disease.  According to WHO, one child dies of malaria every minute, and the absence of an effective vaccine together with the emergence of drug resistant strains foreshadow a possible crisis that will only be resolved by discovery of a mutation-resistant therapy for the disease. 

Through detailed physiological and mechanistic studies of the interplay between the malaria parasite and its human erythrocyte host, it was discovered that the parasite must activate an erythrocyte tyrosine kinase in order to egress from the red cell host at the end of its normal life cycle.  In vitro studies have shown that inhibitors of this erythrocyte kinase lock the malaria parasite into the host cell, ultimately leading to the parasite's death.  Similarly, human clinical trial data testing this kinase inhibitor in malaria patients in Vietnam demonstrated that the inhibitor not only has measurable antimalarial activity as a monotherapy but significantly enhances the current artemisinin-based combination therapy.  ErythroCure is building upon these discoveries to develop more potent and efficacious drugs that exploit this novel mechanism of action.