ミオスタチン拮抗作用による筋肉治療

ミオスタチン拮抗作用による筋肉減少に対する治療のレビュー論文を紹介します。

Han, H.Q.; Mitch, William E: Targeting the myostatin signaling pathway to treat muscle wasting diseases. Current Opinion in Supportive & Palliative Care: 21 October 2011, doi: 10.1097/SPC.0b013e32834bddf9

ミオスタチンという言葉を聞く機会が個人的には増えています。ミオスタチンはTGF-βファミリーの1つのサイトカインで、異化状態のときに体内で増えています。最近、ミオスタチンの分泌を抑制すると筋肉量が増加することが、がんと腎不全の実験モデルで示されました。ミオスタチン拮抗薬が臨床レベルで開発されれば、サルコペニアや悪液質の治療に有効な可能性があります。

悪液質の薬物療法の中では、グレリン受容体作動薬に最も期待していますが、ミオスタチン拮抗薬も今後期待できるかもしれません。臨床応用される日はまだかなり先の話になるかとは思いますので、当面は栄養療法、運動療法、薬物療法（試しに六君子湯やエパデール）の併用が重要だと感じています。

Abstract
Purpose of review: To understand the mechanisms of muscle wasting and how inhibiting myostatin signaling affects them.

Recent findings: Myostatin signaling is critical for the understanding of the pathogenesis of muscle wasting as blocking signaling mitigates muscle losses in rodent models of catabolic diseases including cancer, chronic kidney, or heart failure.

Summary: Muscle wasting increases the risks of morbidity and mortality. But, the reliability of estimates of the degree of muscle wasting is controversial as are definitions of terms like cachexia. Much information has been learnt about the pathophysiology of muscle wasting, including the major role of the ubiquitin-proteasome system (UPS) which along with other proteases degrades protein and limits protein synthesis. In contrast, few successful strategies for reversing muscle loss have been tested. Several catabolic conditions are characterized by inflammation, increased glucocorticoid production, and impaired intracellular signaling in response to insulin and IGF-1. These characteristics lead to activation of the UPS and other proteases producing muscle wasting. Another potential initiator of muscle wasting is myostatin and its expression is increased in muscles of animal models and patients with certain catabolic conditions. Myostatin is a member of the TGF-[beta] family; it suppresses muscle growth and its absence stimulates muscle growth substantially. Recently, pharmacologic suppression of myostatin was found to counteract inflammation, increased glucocorticoids and impaired insulin/IGF-1 signaling and most importantly, prevents muscle wasting in rodent models of cancer and kidney failure. Myostatin antagonism as a therapy for patients with muscle wasting should become a topic of clinical investigation.