AHK2: Duchenne gihar-distrofian potentzial terapeutikoa duen kalstabina modulatzaile berria

Abstract

Duchenne gihar-distrofia (DMD) ikertzeko erabiltzen diren mdx saguak 12 astez tratatu dira AHK2 izeneko molekula berriarekin eta konposatu honek bihotzean duen eragina aztertu da. Batetik, elektrokardiogramak egin zaizkie saguei eta, bestetik, bihotzeko zelulak isolatu eta kardiomiozito hauetan kaltzioarekin lotutako hainbat ezaugarri aztertu dira mikroskopia konfokalean. Lan honetan AHK2-ak nitrosilazio zein fosforilazioak eraldatutako rianodina-hartzaileen funtzioa berrezartzen duela ikusi da, kaltzio txinparta edo spark-en jaitsiera esanguratsua eragiten baitu. Gainera, tratamenduak bihotzaren funtzioa hobetzen duela dirudi, elektrokardiograma bidez sagu gaixoen QTc tartea, bihotzak birpolarizatzeko behar duen denbora, laburtzen duela ikusi baita.

Mdx mice, the most used animal model to research Duchenne muscular dystrophy, were treated for 12 weeks with the novel compound AHK to focus on its effect in the heart. With this aim, heart functionality was analyzed by electrocardiography and, also, cardiomyocytes were isolated from treated mice in order to study the effect on calcium handling by confocal microscopy. In this work it has been shown that AHK2 can modulate the function of the nitrosylated and phosphorylated ryanodine receptor, since it reduces the calcium spark frequency significantly. Moreover, it seems that the treatment improves heart function, decreasing QTc length, time to repolarize during a heartbeat.