Insulin-like growth factor-1 and its derivatives: potential pharmaceutical application for treating neurological conditions.

Insulin-like growth factor-1 and its derivatives: potential pharmaceutical application for treating neurological conditions. Recent Pat CNS Drug Discov. 2013 Aug;8(2):142-60 Authors: Guan J, Mathai S, Liang HP, Gunn AJ Abstract Ischemic brain damage remains a major cause of disability at all ages. This review examines the efficacy, mode of action and mechanisms of insulin-like growth factor (IGF)-1 and its derivatives in animal models of acute brain injury and neurodegenerative conditions, their potential in pharmaceutical developments. IGF-1 reduces cell loss and improves long-term neurological function in animal models. IGF-1 needs to be given within a few hours of the insult. However, the therapeutic window can be extended by mild hypothermia, likely by delaying apoptosis. Nevertheless, the poor central uptake of IGF-1 and its mitogenic potential limit clinical translation. Thus, recent studies have examined related compounds. For example, intravenous infusion of the N-terminal tripeptide of IGF-1 (glycine- proline-glutamate, GPE) can alleviate brain injury and improve long-term function in rats, with a broad effective dose range and a 3-7 hour therapeutic window, but has a short half-life. G-2meth-PE(G-2mPE), a GPE analogue with a longer half-life, is also neuroprotective. GPE/G-2mPE do not interact with IGF receptors and may act by modulating postinjury inflammation, astrogliosis and vascular remodeling. Cyclo-glycyl-proline (cG...
Source: Recent Patents on CNS Drug Discovery - Category: Drugs & Pharmacology Tags: Recent Pat CNS Drug Discov Source Type: research