Potential First-In-Class Migraine Medication
Migraine is the 2nd-most disabling disorder worldwide, due in large part to suboptimal treatment with current medications. While there are a number of recently-approved migraine therapeutics, all of these new drugs target CGRP, a peptide that contributes to migraine in many, but not all patients. Targeting PAR-2 is a completely distinct approach from inhibiting CGRP signaling, and may provide efficacy in patients who are non-responsive to current agents.
Emerging evidence supports a role for the immune system in migraine pathology but current drugs (including triptans and CGRP inhibitors) do not effectively block neuroimmune interactions that can contribute to migraine pain. PAR-2 is activated by proteases released by several distinct types of immune cells, it is expressed on pain-sensing neurons that innervate the cranial meninges (neurons that are essential for headache), and our preclinical modeling shows that our PAR-2 antagonists can block headache behavior induced by multiple proteases associated with the immune system. Importantly, these models show that our PAR-2 antagonists have efficacy without the need to access the central nervous system and they have efficacy even after behavioral responses have developed. These are critical factors as many current medications have CNS side effects and most need to be taken before or very early into an attack to be efficacious.