Track topics on Twitter Track topics that are important to you
CGRP plays a major role in the pathophysiology of migraine. Concomitant, CGRP plays a role in endogenous neurovascular protection from severe vasoconstriction associated with e.g. cerebral or cardiac ischemia. The CGRP antagonistic antibodies Fremanezumab (TEVA Pharmaceuticals) and Erenumab (Novartis/Amgen) have successfully been developed for the prevention of frequent migraine attacks. Whereas these antibodies might challenge endogenous neurovasular protection during severe cerebral or coronary vasoconstriction, potential future therapeutic CGRP agonists might induce migraine-like headaches in migraineurs. In the current study segments of cerebral artery have been used to obtain mechanistic insight of the CGRP-neutralizing anti-body Fremanezumab in neurovascular regulation in vitro. The basilar artery was selected due to its relevance in subarachnoid hemorrhage (SAH). Erenumab is known to block the human CGRP receptor and Fremanezumab to neutralize both human and rat CGRP. Results confirmed that Erenumab does not block the rat CGRP receptor and that Fremanezumab inhibits the vasodilatory effect induced by both human CGRP, rat CGRP and the metabolically stable CGRP analog, SAX in rat basilar artery. Fremanezumab also inhibits the vasodilatory effect of capsaicin in constricted segments of basilar artery. Capsaicin is used as a pharmacological tool to induce secretion of endogenous perivascular CGRP and our studies confirm that the antibody reach the perivascular sensory synaptic cleft and blocks the vasodilatory response of released CGRP in the present in vitro model. Thus, CGRP neutralization might have the mechanistic potential to block vasoprotective responses to severe vasoconstriction provided they reach the site of action and Fremanezumab is an important tool for future investigations of the impact of CGRP physiology.
This article was published in the following journal.
Name: European journal of pharmacology
Fremanezumab is a fully humanized IgG Δa/kappa monoclonal antibody specific for calcitonin gene-related peptide (CGRP) developed and approved for the preventive treatment of migraine in adults. The p...
Most centrally-acting migraine preventive drugs suppress frequency and velocity of cortical spreading depression (CSD). The purpose of the current study was to determine how the new class of periphera...
Cerebral embolism after carotid artery stenting (CAS) is a well-known complication, but cerebral ischemia due to cerebral vasospasm after CAS is rare and has seldom been reported. We describe a patien...
Effects of superficial temporal artery-middle cerebral artery bypass on hemodynamics and clinical outcomes in the patients with atherosclerotic stenosis in the intracranial segment of internal carotid artery and middle cerebral artery.
To observe the effects of superficial temporal artery-middle cerebral artery bypass (STA-MCA bypass) on hemodynamics and clinical outcomes in the patients with atherosclerotic stenosis in the intracra...
Although some authors proposed that coil embolization in middle cerebral artery (MCA) aneurysms is a useful and effective alternative, the characteristics of the aneurysms may be different at each loc...
Prior to administering PF-04427429 to patients we wish to increase the understanding of functional effects associated with calcitonin gene related peptide (CGRP) pathways. This study will ...
The primary objective of the study is to estimate the treatment effect of fremanezumab administered subcutaneously in reducing pain in adult patients with FM. A secondary objective is to e...
The primary objective is to evaluate the efficacy of monthly 225 mg sc fremanezumab in adult patients with migraine and major depressive disorder (MDD) The secondary objectives are to eva...
This expanded access program is designed to make fremanezumab available to patients with EM or CM who have successfully completed (per protocol) Teva-sponsored Study TV48125-CNS-30051 or T...
The purpose of this study is to evaluate the efficacy, safety, and tolerability of monthly and quarterly subcutaneous (sc) injections of fremanezumab compared with sc injections of placebo...
NECROSIS occurring in the ANTERIOR CEREBRAL ARTERY system, including branches such as Heubner's artery. These arteries supply blood to the medial and superior parts of the CEREBRAL HEMISPHERE, Infarction in the anterior cerebral artery usually results in sensory and motor impairment in the lower body.
Pathological conditions of intracranial ARTERIES supplying the CEREBRUM. These diseases often are due to abnormalities or pathological processes in the ANTERIOR CEREBRAL ARTERY; MIDDLE CEREBRAL ARTERY; and POSTERIOR CEREBRAL ARTERY.
Artery formed by the bifurcation of the BASILAR ARTERY. Branches of the posterior cerebral artery supply portions of the OCCIPITAL LOBE; PARIETAL LOBE; inferior temporal gyrus, brainstem, and CHOROID PLEXUS.
A polygonal anastomosis at the base of the brain formed by the internal carotid (CAROTID ARTERY, INTERNAL), proximal parts of the anterior, middle, and posterior cerebral arteries (ANTERIOR CEREBRAL ARTERY; MIDDLE CEREBRAL ARTERY; POSTERIOR CEREBRAL ARTERY), the anterior communicating artery and the posterior communicating arteries.
Artery formed by the bifurcation of the internal carotid artery (CAROTID ARTERY, INTERNAL). Branches of the anterior cerebral artery supply the CAUDATE NUCLEUS; INTERNAL CAPSULE; PUTAMEN; SEPTAL NUCLEI; GYRUS CINGULI; and surfaces of the FRONTAL LOBE and PARIETAL LOBE.
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...
The Top 100 Pharmaceutical Companies
Top 10 biotech and pharmaceutical companies worldwide based on market value in 2015 2015 ranking of the global top 10 biotech and pharmaceutical companies based on revenue (in billion U.S. dollars) Johnson & Johnson, U.S. 74...