Summary
- Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is a cold receptor, somewhat the opposite of the capsaicin receptor (TRPV1), which is a heat receptor.
- TRPA1 is a chemosensor and it has an abundance of agonists, exogenous (cigarette smoke, etc...) and endogenous (prostaglandins, etc…). All neurons that express TRPA1 also express TRPV1.
- Stimulating TRPA1 causes pain.
- Hydra Biosciences is developing TRPA1 antagonists (receptor blocker) to block pain and inflammation.
Analysis
Hydra Biosciences has developed at least 2 TRPA1 antagonists:
- HC-030031 was used in vitro and in vivo pre-clinical studies
- HC-068559 is the candidate compound for clinical studies. It is much more potent.
In pre-clinical studies, HC-030031 does not affect normal cold sensitivity but does block cold hypersensitivity in models of inflammation (CFA). Of note, Non-steroidal Anti-inflammatory Drugs (NSAIDs) do not block cold hypersensitivity and high doses of opiates only partially block cold pain.
Possibly the most significant finding of these pre-clinical studies is that HC-030031 is an anti-inflammatory. The market for new anti-inflammatories are at least as important as those for pain.
The finding that all neurons expressing TRPV1 also express TRPA1, means that the failure of TRPV1 antagonists to reach market might be a great opportunity for TRPA1 antagonists.
Luc Jasmin, MD, PhD consults with leading institutions through GLG
Analyses are solely the work of the authors and have not been edited or endorsed by GLG.
