Soluble CPG15 Compounds as Insulin Receptor and Insulin-Like Growth Factor Receptor Agonists and Antagonists

Technology #12091

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The effects of s-CPG15 and dnCPG15 on the growth factor mediated rescue of cortical neurons from starvation induced apoptosis. (A) is a graph showing the rescue of primary cortical neurons undergoing apoptosis induced by growth factor deprivation by the addition of different growth factors (15, s-CPG15; I, Insulin; IGF-1; B, BDNF; NT-3) but not by the addition of NGF. (*P<0.001). (B) is a graph showing that a dominant negative form of CPG15 (dnCPG15) can block the rescue by s-CPG15, insulin and IGF-1. dnCPG15 had no effect on BDNF or NT-3 induced rescue. (*P<0.001)Graph showing the rescue effect of s-CPG15 can be prevented by inhibitors for the IGF-1- and insulin-receptor. Primary cortical neurons undergoing apoptosis induced by growth factor deprivation were incubated with s-CPG15 alone or in combination with an IGF-1 receptor blocking AB (IGF-1R AB) or with HNMPA, a specific inhibitor of the insulin receptor. While s-CPG15 alone can rescue neurons from starvation-induced apoptosis, this effect was blocked by the IGF-1R blocking AB and the insulin receptor inhibitor. (*P<0.001).
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Inventors
Professor Elly Nedivi
Department of Brain and Cognitive Sciences, MIT
External Link (nedivilab.mit.edu)
Managed By
Jon Gilbert
MIT Technology Licensing Officer
Patent Protection

CPG15 compounds as insulin receptor and insulin-like growth factor receptor agonists

US Patent 7,884,078

Applications

This invention can be used to treat or prevent any disease or disorder associated with aberrant insulin or  insulin-like growth factor 1 signaling, including but not limited to, diabetes, obesity, cancer, hyperglycemia, hypoglycemia, cardiovascular disease, syndrome X, neurodegeneration and Alzheimer’s disease, appetite control, osteoporosis, decreased muscle mass, psoriasis, gigantism, and immune modulation disorders.

Problem Addressed

Improper insulin-regulation of blood glucose levels leads to diabetes and obesity. Likewise, insulin-like growth factor 1 (IGF-1), a single-chain protein that stimulates cell differentiation and proliferation and has a possible role in metabolic pathways, has been implicated in a number of cancers. Insulin and IGF-1 are similar in size, sequence and structure and have low affinity to each other’s receptors: insulin receptor (IR) and IGF-1 receptor (IGF-1R) respectively. This technology includes IR and IGF-1R agonists and antagonists to control the insulin and IGF-1 signaling pathways which are responsible for glucose levels, lipid metabolism, DNA and RNA synthesis, and cellular proliferation.

Technology

This technology includes the discovery of IR and IGF-1R agonists and antagonists. Insulin binding receptor activators such as s-CPG15, CPG15-2, and s-CPG15-2 can act as agonists (either directly or indirectly) to the insulin-binding receptors by activation of signaling pathways or by recruiting downstream signaling proteins. Furthermore, inhibitors of s-CPG15 or CPG15-2 (including inhibitors of s-CPG15-2), such as dominant negative forms of CPG15 or CPG15-2, can block the function of insulin and IGF-1 but not that of other growth factors, such as BDNF and NT-3.  Therefore, s-CPG15 or s-CPG15-2 compounds and inhibitors can be used to treat or prevent any number of disorders associated with aberrant insulin or IGF-1 signaling including the regulation of blood glucose levels.

Advantages

  • Allows treatment for a wide-variety of disorders caused by improper insulin and IGF-1 signaling

  • Antagonists do not block other growth factors