- Bladder pain
- Endometriosis pain
- Hypersensitive cough
- Neuropathic pain
- Sleep apnea
P2X3 receptor antagonists are being evaluated for the potential use in treating a number of hypersensitization disorders. At BELLUS, we are specifically studying our P2X3 receptor antagonist as a potential treatment option for subjects with refractory chronic cough, and subjects with chronic pruritus associated to atopic dermatitis.
It is believed that P2X3, a key sensory receptor in the peripheral nervous system, is responsible for various sensitization reflexes including irritation and pain. Its targeting has been clinically validated as a rational approach for treating symptoms of chronic cough. However, P2X3 receptor antagonism potentially plays a role in a person’s ability to taste likely due to the heterotrimeric nature of the P2X3 receptor and the role the P2X2/3 sub-receptor plays in impairing function.
It is well-known and widely-documented that a P2X3 antagonist with low selectivity has an higher adverse effect on taste, likely due to the inhibition of P2X2/3 receptors on the taste buds. On the other hand, a highly selective P2X3 antagonist is less likely to inhibit P2X2/3 receptors, potentially resulting in decreased cough frequency with minimal taste loss. In the Phase 2 RELIEF trial, BELLUS Health’s highly selective P2X3 antagonist (>1500 fold more selective for P2X3 vs P2X2/3) reduced coughing in chronic cough patients with higher baseline cough count, with less taste alteration.
Based on studied mechanistic similarities between chronic cough and chronic pruritus, BELLUS Health also believes P2X3 receptor antagonists may have an effective therapeutic effect for chronic pruritus associated with atopic dermatitis.
In addition to chronic cough and chronic pruritus, P2X3 receptor antagonists may also have broad applicability across other afferent hypersensitization-related disorders. BELLUS Health is exploring how P2X3 activation can contribute to irritation and pain, and whether inhibition of P2X3 receptors can help treat additional afferent hypersensitization-related disorders.