There is a critical need for the establishment of strategies that will determine the efficacy, safety, and toxicity of genome editing techniques specifically in hematologic diseases.
Recent murine studies and early phase clinical trials demonstrate that pharmacologic “traps” for TGF-beta family members may stimulate erythropoiesis in non-erythropoietin-dependent mechanisms. The molecular details of this process remain to be elucidated. Better understanding of this process, which may markedly decrease the marrow problem of “ineffective erythropoiesis,” may lead to improved therapies in thalassemia,... more »
Thanks to elegant work since the 1990s, many details of the role of iron regulation and metabolism have been elucidated. Recent efforts in academic and pharmaceutical laboratories aim to translate these discoveries into therapies that may alleviate anemia in iron-refractory states (including anemia of inflammation and congenital disorders), and may have important therapeutic effects in non-transfusion-dependent thalassemia,... more »
Three chelators are presently available in the US and much of the world: parenteral deferoxamine, and oral deferasirox, as well as oral deferiprone. Monotherapy is unsuccessful in a significant minority of patients, due to side effects or inadequate response at tolerable doses. Taking a page from enormously successful strategies for combination oral therapy in hypertension, led by NHLBI and others over the past four... more »
While the primary pathophysiology of thalassemia is related to globin gene mutations and unbalanced globin chain expression, the downstream consequences are manifold. Chronic pain turns out to be one of the most important factors identified by patients with transfusion dependent thalassemia major in health-related quality of life surveys and patient-reported outcome measures. Even as therapies aimed and gene editing,... more »