Migraine Target Therapy

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Migraine Target Therapy

Migraine is a debilitating primary headache disorder that often results in missed days at work, loss of productivity and severe disability. It has been ranked as the second-most disabling disease worldwide when it comes to years lived without work; thus, preventive therapies are essential to reduce its destructive effects.

Targeting CGRP for acute and prophylactic migraine treatment offers a promising new option to combat migraine. Anti-CGRP monoclonal antibodies are safe and well tolerated, requiring much less administration than typical daily migraine medications that must be taken. Furthermore, these can be used to treat people who experience intolerable side effects from other medicines or don’t respond to them.

CGRP, a neuropeptide within the calcitonin gene-related peptide family (CGRP), plays an active role in several pathogenic mechanisms associated with migraine. It does this by activating various receptors including 5-HT1D receptors found on intracranial blood vessels and sensory nerve endings of the trigeminal system. Monoclonal antagonising antibodies such as rimegepant or lasmiditan inhibit CGRP receptor activity.

Drugs targeting CGRP for prophylactic migraine prevention are currently in development. These include erenumab, fremanezumab, galcanezumab and eptinezumab; they are administered subcutaneously monthly and have shown to decrease migraine attacks among those treated.

Preventive therapy is an integral part of migraine patient care and particularly beneficial for those at higher risk for future attacks. Unfortunately, many do not receive prophylactic treatment – a major obstacle to effective care that also puts a hefty strain on healthcare systems.

Since 2018, four anti-CGRP monoclonal antibodies have been approved by the US Food and Drug Administration for prophylactic use. They include erenumab by Amgen (Thousand Oaks, CA, USA), fremanezumab by Teva (Malvern, PA, USA), galcanezumab by Eli Lilly (Lunenburg, Germany) and eptinezumab from Lundbeck (Padua, Italy).

Anti-CGRP monoclonal antibodies (mAbs) administered monthly under the skin have shown to significantly reduce migraine attacks in patients. The drugs inhibit calcitonin gene related phosphoprotein (CGRP), found in both central and peripheral nervous systems; it exists as two isoforms: a-CGRP and b-CGRP, with CGRPa more prevalent throughout both CNS/PNS regions relevant to migraine while b-CGRP mostly found within enteric nervous systems.

A-CGRP and b-CGRP possess distinct chemical structures, enabling them to bind with distinct receptors. A-CGRP’s binding sites are located on the surface of a cell membrane, while those for b-CGRP reside inside the nucleus.

Anti-CGRP monoclonal antibodies have been known to target not only the CGRP receptor, but also other targets such as CLR/RAMP1 complex and KATP channels in the brain (primarily limbic system and occipital ganglion). These channels have been associated with migraine and related pain disorders.

Recently, researchers reported that levcromakalim, a selective KATP channel opener, inhibited chronic pain and allodynia in an NTG model of migraine in mice. Furthermore, this agent dilatation superficial temporal arteries and radial arteries, increased MCA velocity, decreased occipital artery pressure, as well as evoked cortical spreading depression in both migraine and non-migraine subjects.

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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: