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Novel Tissue Repair/Growth Factor for the Treatment of Muscular and Nervous Disorders



Background
In muscular and neuronal tissue there is no cell replacement once embryological differentiation is complete at or near birth. Therefore there has to be an effective local cellular mechanism to repair the physical and free radical induced tissue damage that occurs throughout life. If this damage is not repaired quickly the cells die rapidly creating a permanent deficit, as occurs during old age when local tissue repair mechanisms start to break down.

Technology Summary
The cDNA of three human insulin -like growth factor I (IGF-I) splice variants have been cloned in human muscle by researchers at the Royal Free and University College Medical School, University College London. The mRNA of one of these IGF-I splice variants was found to be detectable only in exercised and/or damaged (e.g. stretched or electrically stimulated) muscle. Its expression was found to be related to the level of muscular activity and it was subsequently named 'Mechano Growth Factor' (MGF). The biological activity of MGF has been tested both in vivo by intramuscular injection into mice of the cDNA contained in a suitable muscle expression vector, and in vitro by injection into cultured myocytes. Intramuscular injection of MGF resulted in a 20% increase in muscle wet weight and a 25% increase in mean muscle fibre size after only two weeks, with subcutaneous administration resulting in no significant increase in wet weight of underlying muscle, thus suggesting a localised action.

Development Status
MGF has been found to be expressed in mouse, rabbit and human muscle, with sequence studies showing MGF to have a number of domains, some of which have similar sequences to the liver systemic type of IGF-I, but one which activates muscle stem cells and another that recognises a specific binding protein. The binding protein has been found to be present in abundance in both skeletal and cardiac muscle, where it stabilises MGF and localises its action, thus reducing the risk of potential side-effects on non-target cells/tissue. MGF has not only been found to be expressed in muscle but also in other types of damaged tissue where it up regulates protein synthesis and induces the stem cells required for tissue regeneration. A number of different therapeutic applications of MGF are currently being developed together with academic and commercial collaborators.

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