Summary of Invention

This invention relates to the use of a bacterial toxin called CNF1 on inflammatory pain. CNF1, firstly isolated at Istituto Superiore di Sanità in 1983, is a chromosomally-encoded protein toxin produced by certain strains of Escherichia coli. This toxin possesses an enzymatic activity that induces a highly specific and permanent activation of the small GTPases of Rho family, encompassing three main subfamilies, Rho, Rac and Cdc42. The Rho proteins control a variety of cellular processes, including the cytoskeleton organization and the expression of membrane receptors, and it has been recently suggested a role for these proteins in the mechanisms involved in the neuropathic pain. In the present work, we have demonstrated an activity of CNF1 in the pain perception in experimental animals. More precisely, we have verified that the intracerebroventricular and peripheral injections of CNF1 in mice were followed by a potent analgesic activity towards inflammatory pain, as shown by the significant decrease of licking response in the formalin test. The CNF1 molecule, or part of it, could also be administered sub- coutaneously or intrathecally to counteract inflammatory and postoperative pain. Solution to which problem (s) The deeper knowledge of the mechanisms underlying pain transmission and the clinical practice, have ameliorated the characterization of the different types of pain and pushed for the research of more specific and appropriated therapy. CNF1 modulates the opioid receptors, and this can provide a new way to reduce the dose and the side-effects of morphine, by combining this last drug with the toxin. Possible utilization for the treatment of both acute and chronic inflammatory pain and for postoperative pain. Key applications We propose the use of CNF1 in the treatment of hyperalgesic conditions, such as those linked to degenerative pathologies and to pro-inflammatory pharmacological treatments, particularly in human chronic-degenerative and neoplastic diseases.

Stage of Development: The technology is in the pre-clinical stage with in vivo animal studies ongoing.

Priority Filing in Italy in July 2005

Developmental partnership, Out-license, Sale