O uso de imunoglobulina G em camundongos com distrofia muscular
Alemanha – Imunoglobulina G é utilizada em algumas doenças auto-imunes ou inflamatórias. Neste estudo em camundongos com distrofia muscular foram tratados mensalmente com imunogloblina injetável mensalmente, Os animais tratados apresentaram aumento da força muscular, redução da enzima CK, melhora da função cardíaca e melhora das alterações patológicas dos músculos esqueléticos.
O resumo em inglês pode ser lido abaixo:
(Clinical & Experimental Immunology, 2014) Human immunoglobulin G for experimental treatment of Duchenne muscular dystrophy
J. Zschüntzsch, P. Jouvenal, Y. Zhang, F. Klinker, M. Tiburcy, D. Malzahn, D. Liebetanz, H. Brinkmeier and J. Schmidt – Germany
Duchenne muscular dystrophy is the most common inherited disorder of the skeletal muscle. It is caused by a mutation in the dystrophin gene on the X chromosome. Subsequent lack of the dystrophin protein leads to impaired stability of the myocytoskeleton and reduced contraction functionality of skeletal muscle fibres [1, 2]. This devastating myopathy leads to an enormous burden of disease and often death before 30 years of age. Despite a tremendous effort with numerous clinical trials that aimed to correct the gene defect, so far no effective therapy is available [3]. Current standard treatment includes the use of glucocorticosteroids, which aims to reduce the profound bystander inflammation in the skeletal muscle [4]. However, treatment with glucocorticosteroids is hampered by severe long-term side effects.In search for a more effective and tolerable treatment we used the mdx mouse, an established model of the disease, which harbours a homologue mutation of the dystrophin gene. Mice received 2 g/kg human immunoglobulin (Ig)G once per month compared to sham treatment of equal volume, administered by intraperitoneal injection. Each mouse was housed in a separate plastic cage equipped with a computerized running wheel, which continuously recorded the running behaviour and provided parameters such as number of runs, daily and total distance and distance per run [5]. Clinical parameters included body weight, grip-strength assessment and running-wheel performance. The cardiac function was monitored by ultrasound and at the end of the experiment mice were killed for ex vivo contraction analysis. Muscle pathology and expression profile of inflammatory mediators was assessed by immunohistochemistry and quantitative polymerase chain reaction (qPCR). During the early phase of the disease, IgG led to an improved running-wheel performance and ex vivo contraction analysis displayed an elevated endurance. In line with this, myopathic changes in the skeletal muscle were ameliorated and cellular infiltration was reduced. At the same time, release of the muscle enzyme creatine kinase was diminished. In the late phase of the disease, running-wheel performance and grip strength were improved upon treatment with IgG. This was accompanied by a superior cardiac function, as evidenced by ultrasound. In tissue sections of skeletal muscle and diaphragm, myopathic alterations and infiltration by inflammatory cells were reduced. Collectively, the results demonstrate a beneficial effect of human IgG in the treatment of mdx mice. This suggests that IgG may be a promising option for the future treatment of Duchenne muscular dystrophy. Apart from a monotherapeutic approach, IgG could potentially be of value in combination with gene therapy. A clinical proof-of-concept trial is warranted to study the effect of IgG in Duchenne muscular dystrophy.
Fonte: http://distrofiamuscular.net/principal.htm
