Clifford J. Woolf,Michael Costigan,Robert Griffin,Irmgard Tegeder
申请号：
US13649776
公开号：
US20130210826A1
申请日:
2012.10.11
申请国别(地区):
US
年份:
2013
代理人:
摘要：
The present invention features methods and compositions for preventing, reducing, or treating a traumatic, metabolic, or toxic peripheral nerve lesion or pain including neuropathic pain, inflammatory, and nociceptive pain by administering to a mammal a compound that reduces expression or activity of BH4. This reduction may be achieved by reducing activity of a BH4 synthetic enzyme, including GTP cyclohydrolase, sepiapterin reductase, or dihydropteridine reductase antagonizing the cofactor function of BH4 or BH4-dependent enzymes or blocking BH4 binding to membrane bound receptors. The invention provides methods for diagnosing pain or a peripheral nerve lesion in a mammal by measuring levels of BH4 or its metabolites in biological sample or the levels or activity of any one of the BH4 synthetic enzyme in tissue samples of a mammal. Disclosed are screening methods that use BH4 or BH4 synthetic enzymes, BH4-dependent enzymes, and BH4-binding receptors to identify therapeutics for the treatment, prevention, or reduction of pain.
