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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on November 11, 2005; DOI: 10.1124/jpet.105.095844

0022-3565/06/3163-1122-1129$20.00
JPET 316:1122-1129, 2006
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NEUROPHARMACOLOGY

TrkAd5: A Novel Therapeutic Agent for Treatment of Inflammatory Pain and Asthma

Judy J. Watson, Mark S. Fahey, Edwin van den Worm, Ferdi Engels, Frans P. Nijkamp, Paul Stroemer, Steve McMahon, Shelley J. Allen, and David Dawbarn

Molecular Neurobiology Unit, Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Bristol, United Kingdom (J.J.W., M.S.F., S.J.A., D.D.); Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands (E.v.d.W., F.E., F.P.N.); ReNeuron Ltd., Guildford, Surrey, United Kingdom (P.S.); and Neurorestoration Group and London Pain Consortium, King's College London, London, United Kingdom (S.M.)

Elevated levels of nerve growth factor have been linked to the onset and persistence of many pain-related disorders and asthma. Described here are the design, expression, refolding, and purification of a monomeric (nonstrand-swapped) form of the binding domain of the nerve growth factor receptor, designated TrkAd5. We have shown that TrkAd5 produced recombinantly binds nerve growth factor with picomolar affinity. TrkAd5 has been characterized using a variety of biophysical and biochemical assays and is shown here to be stable in both plasma and urine. The palliative effects of TrkAd5 are demonstrated in animal models of inflammatory pain and allergic asthma. We conclude that TrkAd5 will prove effective in ameliorating both acute and chronic conditions where nerve growth factor acts as a mediator and suggest a role for its application in vivo as a novel therapeutic.

Received September 20, 2005; accepted November 10, 2005.

Address correspondence to: Dr. Shelley J. Allen, Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Dorothy Hodgkin Bldg., Whitson St., University of Bristol, Bristol BS1 3NY, UK. E-mail: shelley.allen{at}bristol.ac.uk




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[Abstract] [Full Text] [PDF]


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