Potencial terapêutico do IGF peguilato em dois modelos de distrofia muscular
Australia – existem inúmeras pesquisas prévias com o IGF-1 em modelos de distrofia muscular; nesta pesquisa os autores testaram em dois modelos de distrofia o IGF-1 peguilato que tem um efeito mais prolongado; no modelo de distrofia com menor grau de lesão muscular os autores observaram um efeito benéfico que não foi observado nos camundongos com a forma de distrofia mais grave; o seu uso poderia ser útil nas formas iniciais da doença ou quando houvesse algum grau de lesão aguda dos músculos, por trauma por exemplo.
O resumo em inglês pode ser lido abaixo:
(Growth Hormone & IGF Research, 2012) Therapeutic potential of PEGylated insulin-like growth factor I for skeletal muscle disease evaluated in two murine models of muscular dystrophy
Stefan M. Gehrig, Chris van der Poela, Andreas Hoeflich, Timur Naim, Gordon S. Lynch, Friedrich Metzger – Australia
Objective: Duchenne muscular dystrophy (DMD) is a fatal monogenetic disease with affected males displaying severe and progressive muscle wasting and weakness eventually leading to premature death. Possible therapeutic benefits of insulin-like growth factor I (IGF-I) have been studied extensively in various models of muscle disease and DMD with IGF-I as a mediator of improved skeletal muscle regeneration by enhancing myoblast proliferation and differentiation.
Design: We tested the efficacy of a novel IGF-I analogue, a polyethylene glycol modified IGF-I (PEG-IGF-I), to ameliorate the pathophysiology of muscular dystrophy in two mouse models of DMD. We used mdx mice which lack dystrophin (as in DMD) but exhibit only a relatively mild phenotype, and the dko mouse which is a transgenic model lacking utrophin in addition to dystrophin, and which exhibits a more severe, lethal phenotype like that in DMD.
Results: In young mdx mice, twice-weekly PEG-IGF-I s.c. injections for 6 weeks protected the diaphragm muscle against fatigue and the tibialis anterior (TA) muscle against contraction-induced injury. However, this beneficial effect of PEG-IGF-I was less pronounced in mdx mice when treatment was initiated later in adulthood. In severely affected dko mice PEG-IGF-I treatment did not affect pathophysiological parameters including animal survival.
Conclusions: These data suggest a therapeutic benefit with PEG-IGF-I treatment only in mild muscle pathologies, since its potential to ameliorate the pathophysiology in models of severe muscular dystrophies was limited. Treatment should be initiated only for mild muscle pathologies if functional benefits are to be realised and therefore may be relevant as a short-term therapy to hasten the functional repair of otherwise healthy muscles after injury.
