Cluster Headaches

Cluster headache (CH) is a primary headache disorder and the most common of the group of headache disorders called trigeminal autonomic cephalalgias (TAC). Its symptoms include recurrent headaches of extreme intensity, accompanied by autonomic symptoms and restlessness. The diagnosis of CH involves excluding other primary headaches and secondary headaches and is based primarily on the patient's symptoms. Currently, there is no cure for CH, but drugs and other treatments can help reduce the incidence and severity of attacks. Short-term drugs such as corticosteroids, ergotamine are taken until one of the long-term medications start working. Long-term drugs, including calcium channel blockers, lithium carbonate and anti-seizure medications, are taken throughout the cluster period. Treatment of CH usually consists of two aspects: the treatment of an acute attack, in which the ongoing attack is effectively aborted, and preventive treatment, in which daily medication is administered to reduce the number of attacks.

Fig.1 Schematic peripheral and central pathway representation summarizing the pathogenesis of CH. (May, 2018)

Calcitonin-gene-related peptide (CGRP) signaling is known to be affected in vascular, inflammatory, as well as neurological diseases. During CH attacks, the trigeminal-autonomic reflex is activated provoking vasodilation of cranial arteries by the release of vasodilatory molecules, including CGRP, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP). Among the various targets, CGRP is the most studied one. CGRP functional blockade alleviates neurogenic inflammation and reduces pain pathway sensitization. Two types of CGRP function-blocking modalities, monoclonal antibodies (mAbs), and small molecules, have been designed to target the CGRP ligands and CGRP receptors, namely ALD403 (eptinezumab), AMG 334 (erenumab), LY2951742 (galcanezumab), TEV-48125 (fremanezumab) and MK-1602 (ubrogepant).

Fig.2 The GPCR receptor and main sites of action for CGRP in CH. (Carmine, 2020)

Creative Biolabs summarizes the potential targets in CH research and offers corresponding products as well as high-quality customized services for our clients. Our services and products include but are not limited to the neural antibodies, small molecules inhibitors, agonists, antagonists, recombinant proteins and customized assay kits. We offer comprehensive services and the best products to aid your disease research. Please feel free to contact us for more information.

References

1. May, A.; et al. Cluster headache. Nature Reviews Disease Primers. 2018, 4(1): 1-17.
2. Carmine, Belin. A.; et al. Calcitonin Gene-Related Peptide (CGRP) and Cluster Headache. Brain Sciences. 2020, 10(1): 30.