潛力案源

- Sickle cell disease and β–thalassemia are the most common monogenic mutation diseases in the world. Traditional treatments include blood transfusion and bone marrow transplantation. However, both of these approaches have disadvantages for patients. - Pharmacotherapy is another strategy to treat the patients. Hydroxyurea (HU) was the only drug (HbF inducer) approved by US-FDA in the past twenty years. However, many side effects of HU have been reported, including myelosuppression, reproductive toxicity and non-responseness (25% of the patients) to HU treatment. Recently, three new drugs: L-glutamine (reduce VOC), Crizanlizumab (reduce VOC) and Voxelotor (HbS polymerization inhibitor) were approved by US-FDA to treat the sickle cell disease. However, the mechanism of L-glutamine is unclear and it can only reduce the complications; Crizanlizumab needs IV infusion and it also can only reduce the complications. The cost of Crizanlizumab is very expensive; Voxelotor can inhibit the HbS polymerization (the cause of SCD), but the cost of Voxelotor is much higher than HU. From the result of phase III clinical trial, 40 % of patients did not have the response. - Our team focuses on the identification and development of better HbF-inducing compounds including AS-28, because HbF not only can inhibit HbS polymerization in SCD, but it also can substitute for the insufficient HbA in β-thalassemia. - AS-28 shows better HbF-inducing efficacy than HU, in erythroid cells including those non-responsive to HU. Thus, AS-28 could be a superior next-generation of HbF inducer to treat sickle cell disease and β-thalassemia