Co-factors for trophic factors, and methods of use thereof

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 14/81 (2006.01) A61K 35/12 (2006.01) A61K 38/00 (2006.01) A61K 38/14 (2006.01) A61K 38/57 (2006.01) C07K 14/00 (2006.01) C07K 16/40 (2006.01) C12N 5/00 (2006.01) C12N 5/02 (2006.01) C12N 5/06 (2006.01) C12Q 1/00 (2006.01) G01N 33/53 (2006.01) G01N 33/554 (2006.01)

Patent

CA 2354378

The present invention is based on the discovery and isolation of a co-factor for trophic factors. It has been discovered that trophic factors require a co- factor to stimulate and/or potentiate the trophic factor activity and/or specificity. This was clearly identified in low density cells where trophic factors are unable, or at best, at minimal levels, able to proliferate undifferentiated cells without a co-factor. In a particular embodiment of the present invention, there is provided a composition comprising glycosylated cystatin C (CCg), an FGF co-factor that stimulates proliferation of neural and fibroblast associated undifferentiated cells. The N-glycosylation of cystatin C is required for its activity. Moreover, CCg acts in cooperation with basic fibroblast growth factor (FGF-2) to induce neural progenitor cell proliferation.

La présente invention est fondée sur la découverte et l'isolement d'un cofacteur pour facteurs trophiques, découverte selon laquelle un cofacteur est requis pour stimuler et/ou potentialiser l'activité et/ou la spécificité des facteurs trophiques. Cela a été clairement identifié dans les cellules à faible densité où les facteurs trophiques ne sont pas capables ou sont capables, au mieux, à des niveaux minimes, de faire proliférer des cellules indifférenciées sans cofacteur. Dans un mode de réalisation particulier, la présente invention concerne une composition comprenant une cystatine C glycosylée (CCg), un cofacteur de facteur de croissance des fibroblastes (FGF), qui stimule la prolifération de cellules nerveuses indifférenciées associées à des fibroblastes. La N-glycosylation de la cystatine C est requise pour son activité. De plus, la CCg agit en coopération avec un facteur de base de croissance des fibroblastes (FGF-2) pour induire une prolifération de cellules souches nerveuses.

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