Conjugates of galactose-binding lectins and clostridial...

A - Human Necessities – 61 – K

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A61K 47/48 (2006.01) A61K 35/74 (2006.01) A61K 38/16 (2006.01) A61K 38/48 (2006.01) A61P 25/04 (2006.01) A61P 29/00 (2006.01) C07K 14/33 (2006.01) C07K 19/00 (2006.01) C12N 9/52 (2006.01) C12P 21/02 (2006.01)

Patent

CA 2306350

A class of novel agents that are able to modify nociceptive afferent function is provided. The agents may inhibit the release of neurotransmitters from discrete populations of neurones and thereby reduce or preferably prevent the transmission of afferent pain signals from peripheral to central pain fibres. They comprise a galastose-binding lectin linked to a derivative of a clostridial neurotoxin. The derivative of the clostridial neurotoxin comprises the L-chain, or a fragment thereof, which includes the active proteolytic enzyme domain of the light (1.) chain, linked to a molecule or domain with membrane translocating activity. The agents may be used in or as pharmaceuticals for the treatment of pain particularly chronic pain.

L'invention concerne une classe de nouveaux agents capables de modifier la fonction afférente nociceptive. Ces agents peuvent inhiber la libération de neurotransmetteurs par des populations discrètes de neurones et réduire ainsi ou, de préférence, prévenir la transmission des signaux de douleur afférents des fibres nociceptives périphériques vers les fibres nociceptives centrales. Ces agents comprennent une lectine fixatrice de galactose liée à un dérivé d'une neurotoxine clostridiale. Le dérivé de neurotoxine clostridiale comprend la chaîne légère ou un fragment de cette dernière qui comprend le domaine enzymatique protéolytique actif de la chaîne légère (L), liée à une molécule ou à un domaine présentant une activité de translocation membranaire. Ces agents peuvent être utilisés seuls ou combinés à d'autres médicaments, pour le traitement de la douleur, en particulier de la douleur chronique.

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