UNIGE document Doctoral Thesis
previous document  unige:32133  next document
add to browser collection

Role of oxidative stress and calcium regulation in Duchenne muscular dystrophy: pharmacological investigations

Defense Thèse de doctorat : Univ. Genève, 2013 - Sc. 4607 - 2013/10/24
Abstract Duchenne Muscular Dystrophy (DMD) is the most common and most severe myopathy. Currently, no cure exists for DMD and novel pharmacotherapy holds the promise of being the fastest route for reaching the patients until a curative genetic therapy is delivered. Towards this end, three drug candidates were evaluated in DMD models. The first was doxorubicin which inhibited phospholipase A2 activity and reduced Ca2+ influx through stretch-activated channels, both reported to be overactive in dystrophic cells. Dystrophic muscles treated with doxorubicin were protected from damaging eccentric contractions. We have also tested the classical NADPH oxidase inhibitor apocynin and its synthetic dimer, diapocynin. Our in vitro and in vivo results show that diapocynin holds a superior therapeutic potential. In conclusion, the work presented in this thesis presents novel drug candidates that can be developed further as potential pharmacotherapeutic treatment for DMD. It also sheds light on the pathways involved in DMD pathogenesis.
Keywords Duchenne muscualr dystrophyStretch activated channelsStore operated channelsPhospholipase A2NADPH oxidaseDoxorubicinApocyninDiapocyninMuscle
URN: urn:nbn:ch:unige-321331
Full text
Thesis (3.2 MB) - public document Free access
(ISO format)
ISMAIL, Hesham. Role of oxidative stress and calcium regulation in Duchenne muscular dystrophy: pharmacological investigations. Université de Genève. Thèse, 2013. doi: 10.13097/archive-ouverte/unige:32133 https://archive-ouverte.unige.ch/unige:32133

702 hits



Deposited on : 2013-12-16

Export document
Format :
Citation style :