We are smart enough to know all the genes in a cell. We believe we can be smart enough to tell the cell what to do.
EPI01 For Sickle Cell Disease and Thalassemia
Why are we testing EPI01, a fetal hemoglobin inducer for clinical use in sickle cell disease and thalassemia?
- Until now there is no cure available for the sickle cell disease. The current therapies neither target the fundamental cause of the disease or slow the progression.
- Sickle cell disease is driven by the aggregation and precipitation of less soluble sickle cell hemoglobin (HbS) in red blood cells—this destroys red blood cells and blocks blood vessels, causing organ damage, pain crisis, and early death.
- Fetal hemoglobin (HbF), expressed in red blood cells in babies, mixes with sickle cell hemoglobin and promotes HbS dissolution. Some sickle cell individuals who naturally express high levels of fetal hemoglobin beyond infancy thus receive some protection from sickle complications.
- Numerous clinical observations show that the severity of sickle cell disease and β-thalassemia is ameliorated via increased production of HbF.
- Our goal is to dilute the mutated HbS containing blood cells with HbF to ensure better tissue oxygenation and thus prevent vascular occlusion in sickle cell patients.
- Drug therapy with hydroxyurea helps ramp up fetal hemoglobin in some patients and reduces the number of painful episodes characteristic of sickle cell. But hydroxyurea is not uniformly effective and at approved doses it is cytotoxic (cell killing) with unwarranted side effects.
- New gene therapy and gene editing technologies, including CRISPR, attempts to induce fetal hemoglobin. But the Gene therapy approaches is limited in potency and sustainability. There are many advantages of EPI01 (a simple oral approach) over gene therapy (safety hurdles with complex gene addition or deletion).
- Fetal hemoglobin production is switched OFF soon after birth in most of us. Normally, the Turning OFF of HbF & Turning ON of adult Hb in babies is controlled by OFF enzyme DNMT1.
- Our goal is to develop a safe, orally available EPI01 to increase fetal hemoglobin by depleting the OFF genetic switch, involved in shutting OFF the fetal hemoglobin gene from infancy onward.