Migraine, a headache for all seasons

Unlike many conditions, migraine can be hard to define. There are no identifying biological markers (yet) and migraine is still very much defined subjectively by the physician and the sufferer. Classically, migraine is often associated with episodic pain in one side of the head and/or a variety of other symptoms. As such, considering other brain centric conditions such as autism, ADHD, schizophrenia etc are thought to exist within a spectrum, migraine should probably be considered in the same light. For many sufferers, there is a plethora of Occam Razor type associations linking environmental factors to symptom onset but for many others such linkages remain a mystery. However, with so many potential paths to migraine onset, is it reasonable to expect the resolution of migraine symptoms to be restricted to a few essential pathways? Are there such nexus points residing within the maelstrom of cellular signalling critical to the onset and subsequent alleviation of pain and other migraine associated symptoms? Are clinical trials, designed to target symptoms, unintentionally hampered by the very patients they are trying to help?; with subjects chosen because they satisfy the gross morphology of certain symptoms but from an underlying migraine onset point of view are unfortunately lumbered with a ‘not all paths lead to Rome’ route planner. Yet, judging by the number of pipeline migraine products hovering just out of each, a major target of particular focus for pharma is the calcitonin gene-related peptide (CGRP) pathway. There are a number of monoclonal antibodies, erenumab, galcanezumab, fremanezumab, eptinezumab as well as chemical entities, atogepant, ubrogepant, rimegepant, all competing to be part of the story. Has the targeting of the CGRP pathway demonstrated benefits in some migraine sufferers; yes. Will therapeutic agents targeting the CGRP pathway constitute a valuable treatment option; probably yes. Will targeting the CGRP pathway be the definitive word in treating migraine sufferers; no. Until we truly understand the variable processes involved in developing migraine in the first place, relieving symptoms for all sufferers will remain very much of a game of catch them if you can.

Gary Paterson PhD, Evidence and Information Manager

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