Minihepcidins improve ineffective erythropoiesis and splenomegaly in a new mouse model of adult ß-thalassemia major.

Minihepcidins are hepcidin agonists that have been previously shown to reverse iron overload and improve erythropoiesis in mice affected by non-transfusion-dependent thalassemia. Given the extreme anemia that occurred with the previous model of transfusion-dependent thalassemia, that model was inadequate for investigating whether minihepcidins can improve red blood cell quality, lifespan and ineffective erythropoiesis. To overcome this limitation, we generated a new murine model of transfusion-dependent thalassemia with severe anemia and splenomegaly, but sufficient red cells and hemoglobin production to test the effect of minihepcidins. Furthermore, this new model demonstrates cardiac iron overload for the first time. In the absence of transfusions, minihepcidins improved red blood cell morphology and lifespan as well as ineffective erythropoiesis. Administration of a minihepcidin in combination with chronic red blood cell transfusion further improved the ineffective erythropoiesis and splenomegaly and reversed cardiac iron overload. These studies indicate that drugs such as minihepcidins have therapeutic potential for patients with transfusion-dependent thalassemia.

A new deletion in 5'-end of dystrophin gene removing M and P promoters and dystrophin muscle enhancers.

We describe a 3-year-old boy who, at age of 8 months, during investigations for upper respiratory tract infection was found to have an incidental grossly elevated CK of 20,000 UI/l. Investigations showed only mild calf hypertrophy and absent Gower's sign, normal cognitive function. Electromyography (EMG) showed myopathic features. Electrocardiography and echocardiography were normal. His muscle biopsy revealed myopathic features indicating Duchenne-type dystrophy. Immunohistochemistry for dystrophin N-terminal, C-terminal and mid-rod antibodies analysis showed the complete absence of dystrophin in the muscle fibers. Genetic studies showed a 141.1 Kb deletion removing muscle promoter, muscle exon 1, Purkinje promoter, Purkinje exon 1, dystrophin muscle enhancers similar to one previously reported in a DMD patient who exhibited some residual expression of dystrophin. The difference in dystrophin expression between these two patients might be due to the extension of deletions. The precise delimitation of the macrodeletion here described provides a better understanding of functional organization of the 5' end of the DMD gene.