Methods for modulating the axonal outgrowth of central...

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A61K 31/70 (2006.01) A61K 31/52 (2006.01) A61K 31/7076 (2006.01)

Patent

CA 2302156

Methods and compositions for modulating the axonal outgrowth of central nervous system neurons are provided. Methods for stimulating the axonal outgrowth of central nervous system neurons following an injury (e.g., stroke, Traumatic Brain Injury, cerebral aneurism, spinal cold injury and the like) and methods for inhibiting the axonal outgrowth of central nervous system neurons in conditions such as epilepsy, e.g., post traumatic epilepsy, and neuropathic pain syndrome, are also provided. These methods generally involve contacting the central nervous system neurons with a purine nucleoside, or analog thereof. Preferably, inosine or guanosine is used to stimulate axonal outgrowth and 6-thioguanine is used to inhibit axonal outgrowth. The methods and compositions are particularly useful for modulating the axonal outgrowth of mammalian central nervous system neurons, such as mammalian retinal ganglion cells. Pharmaceutical and packaged formulations that include the purine nucleosides, and analogs thereof, of the invention are also provided.

L'invention concerne des procédés et des compositions permettant de moduler l'excroissance axonale des neurones du système nerveux central. L'invention concerne aussi des procédés de stimulation de l'excroissance axonale des neurones du système nerveux central à la suite de lésions cérébrales (p. ex. accidents cérébrovasculaires, lésion traumatique du cerveau, anévrisme artériel cérébral, traumatisme de la colonne vertébrale et lésions analogues) et des procédés d'inhibition de l'excroissance axonale des neurones du système nerveux central lors de maladies telles que l'épilepsie, par exemple épilepsie post-traumatique et syndrome de douleur névropathique. Ces procédés consistent normalement à mettre en contact les neurones du système nerveux central avec un nucléoside purique ou une molécule analogue. L'inosine ou la guanosine est de préférence utilisée pour stimuler l'excroissance axonale et la 6-thioguanine est utilisée pour inhiber l'excroissance axonale. Les procédés et les compositions sont particulièrement utiles pour la modulation de l'excroissance axonale des neurones du système nerveux central chez le mammifère, telles que les cellules ganglionnaires rétiniennes. Les formulations pharmaceutiques et conditionnées renfermant les nucléosides puriques et molécules analogues font aussi l'objet de cette invention.

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