The General Hospital Corporation

Children's Medical Center Corporation

Michael Costigan

Clifford J Woolf

Irmgard Tegeder

Alban A Latremoliere

Alexandra S Latini

Robert Griffin

Nick A Andrews

Described herein are methods and assays relating to the inhibition of sepiapterin reductase and measuring said inhibition by measuring the level of sepiapterin. In some embodiments, the methods can further relate to treating a subject with BH4 and/or BH2.

Methods and assays relating to sepiapterin reductase inhibition

The present invention features methods and compositions for preventing, reducing, or treating a traumatic, metabolic or toxic peripheral nerve lesion or pain including, for example, neuropathic pain, inflammatory and nociceptive pain by administering to a mammal in need thereof a compound that reduces the expression or activity of BH4. According to this invention, this reduction may be achieved by reducing the enzyme activity of any of the BH4 synthetic enzymes, such as GTP cyclohydrolase (GTPCH), sepiapterin reductase (SPR), or dihydropteridine reductase (DHPR); by antagonizing the cofactor function of BH4 on BH4-dependent enzymes; or by blocking BH4 binding to membrane bound receptors. The compounds of the invention may be administered alone or in combination with a second therapeutic agent.

Methods for treating pain

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Cambridge, MA, United States of America

Michael Costigan