Enzyme-deficient c3 botulinum protein species and their use...

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/31 (2006.01) A61K 31/7088 (2006.01) A61K 38/16 (2006.01) A61K 39/08 (2006.01) A61K 48/00 (2006.01) A61P 25/28 (2006.01) C07K 14/33 (2006.01) C07K 16/12 (2006.01) G01N 33/566 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2465371

The present invention is directed to nucleotide sequences and their encoded enzyme-deficient proteins and peptides which regulate neurite especially axonal growth, recognitions agents thereto, and the therapeutic and diagnostic uses of such proteins and peptides. The invention relates also to the use of enzyme-deficient or enzymatic inactive C3 proteins/peptide-derivatives derived from Clostridium botulinum for regulation of the growth, expansion and/or differentiation of neurons and neuronal stem cells as well as the regeneration of neurons. In a specific embodiment of the invention, proteins and peptides may be used to promote the regeneration of neuronal axons over long distances following spinal cord damage. The proteins and peptides allow neurite especially axonal outgrowth - without actions on glial cells - in nervous system tissue in vivo and in vitro. They may have important uses in the treatment of central nervous system damage and degenerative nerve diseases.

La présente invention concerne des séquences nucléotidiques et leurs protéines et peptides à déficience enzymatique qui régulent la croissance des neurites, notamment la croissance axonale, des agents de reconnaissance, et les utilisations thérapeutiques et diagnostiques desdites protéines et desdits peptides. L'invention concerne également l'utilisation de protéines/dérivés peptidiques C3 inactifs enzymatiques ou à déficience enzymatique dérivés du Clostridium botulinum pour réguler la croissance, l'expansion et/ou la différentiation de neurones et de cellules embryonnaires neuronales ainsi que pour régénérer les neurones. Selon un mode de réalisation spécifique de l'invention, des protéines et des peptides peuvent être utilisés pour favoriser la régénérescence d'axones neuronaux sur de longues distances suite à une lésion de la moëlle épinière. Lesdites protéines et lesdits peptides permettent l'excroissance des neurites, notamment l'excroissance axonale - sans action sur les cellules gliales - dans les tissus de système nerveux in vivo et in vitro. Ils peuvent notamment être utilisés dans le traitement de lésions du système nerveux central et de maladies neurodégénératives.

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