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

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Received for publication September 20, 2005.
Revised November 10, 2005.
Accepted for publication November 10, 2005.

TrkAd5: A novel therapeutic agent for treatment of inflammatory pain and asthma

Judy J Watson 1, Mark S Fahey 1, Edwin van den Worm 2, Ferdi Engels 2, Frans P Nijkamp 2, Paul Stroemer 3, Steve McMahon 4, Shelley J Allen 1*, David Dawbarn 1

1 University of Bristol 2 University of Utrecht 3 ReNeuron Ltd 4 Kings College London

* Address correspondence to: E-mail: shelley.allen{at}bristol.ac.uk

Abstract

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 (non strand-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.


Key words: asthma, cystitis, nerve growth factor (NGF), pain, therapeutic, tyrosine receptor kinase A (TrkA)


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Antibodies to Nerve Growth Factor Reverse Established Tactile Allodynia in Rodent Models of Neuropathic Pain without Tolerance
J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 282 - 287.
[Abstract] [Full Text] [PDF]


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