A Fresh Approach to Migraine Therapy

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A Fresh Approach to Migraine Therapy

A novel approach to migraine treatment seeks to inhibit calcitonin gene-related peptide (CGRP) receptor. CGRP plays an integral role in migraine pain by increasing sensitivity of the trigeminal nerves to visual, auditory and other stimuli. To combat this condition, several drugs have been developed; small-molecule antagonists like erenumab, rimegepant and ubrogepant; as well as monoclonal antibodies targeting CGRP receptors.

Cgrp-receptor antagonists have proven effective, but they do come with potential side effects such as injection site pain, constipation and muscle spasms. Despite their benefits, these drugs cannot guarantee complete relief from migraine headaches; further research is necessary to confirm their safety for long-term usage.

Fremanezumab, an oral CGRP receptor antagonist, was approved by the US Food and Drug Administration in September 2018 for migraine prophylaxis. It can be administered monthly as 225 mg subcutaneous injection or quarterly at 675 mg subcutaneous injection. Phase 3 trials have demonstrated its efficacy in both episodic and chronic migraine, with significantly fewer headache days with fremanezumab than with placebo (Table 2).

Anti-CGRP monoclonal antibodies (mAbs) are peptides that bind to the CGRP receptor and have a long half-life. Given they’re parenterally administered, anti-CGRP mAbs may be more tolerable than other preventive therapies and even help improve patient compliance and adherence to treatment.

Migraine is a debilitating neurological disorder that causes intense headaches that can last hours or days, often with nausea, vomiting and extreme sensitivity to light and sound. Patients may also experience visual disturbances called an aura which may include flashes or spots of light.

CGRP-receptor antagonists differ from most other medications used to treat headaches in that they do not cross the blood-brain barrier but instead target CGRP receptors on trigeminal nerve fibers outside of the brain, allowing them to target perivascular trigeminal sensory fiber terminals which often become sensitized in migraine patients.

According to a new study published online October 27, 2022 by Greg Dussor of the University of Texas at Dallas in the US, researchers led by Professor Greg Dussor have discovered that inhibiting an isoform of MNK1 (an enzyme vital in translation regulation) can alleviate hypersensitivity symptoms in mouse models of migraine. They observed reduced sensitivity to both visual and auditory stimuli when this MNK was inhibited.

This work adds to the growing body of evidence suggesting ion channels are important gatekeepers of pain and may be an ideal target for migraine therapeutics. These channels regulate many essential cell functions, including chemical signalling between neurons.

These ion channels, also referred to as “tiny transportation tunnels” in the brain, allow cells to move from one region to another. During a migraine attack, these ion channels become disrupted.

Studies have demonstrated that CGRP-receptor antagonists, such as erenumab and eptinezumab, can reduce headache attacks in those suffering from migraine. Compared with small-molecule CGRP receptor antagonists, these monoclonal antibodies (mAbs) are more effective at preventing migraine attacks with fewer side effects.

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- Welcome, SoundTherapy.com lowers anxiety 86%, pain 77%, and boosts memory 11-29%. Click on the brain to sign up or share with buttons below to help others: