Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects

Lukács, Miklós; Tajti, János; Fülöp, Ferenc; Toldi, József; Edvinsson, Lars; Vécsei, László

doi:10.2174/0929867324666170712163437

Cited by 48 publications

(43 citation statements)

References 134 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although the role of neurogenic inflammation and possibly immune dysfunction in migraine pathophysiology has gained much attention over the last few decades, the exact pathogenesis of migraine headache has not been fully understood as yet. The involvement of the inflammatory system in this process may be mediated through different mechanisms including augmented levels of proinflammatory factors in the nervous system and increased release of a number of neuro‐inflammatory factors (eg, NO, CGRP, SP, vasoactive intestinal peptide [VIP], glutamate [Glu], pituitary adenylate cyclase‐activating polypeptide [PACAP], and neurokinin A) that result in vasodilation in arteries and disturbances in the regulation of mast cells and ultimately pain sensitization in the head . On the other hand, the potential anti‐inflammatory and immune regulating abilities of vitamin D can be beneficial in reducing the risk of migraine occurrence in susceptible individuals.…”

Section: Discussionmentioning

confidence: 99%

Serum Vitamin D Status in a Group of Migraine Patients Compared With Healthy Controls: A Case–Control Study

et al. 2018

View full text Add to dashboard Cite

Objective The association between serum vitamin D and migraine is investigated in this research.s Background Although the pathogenesis of migraine headache is not fully understood, the possible role of inflammation and disturbed immune system has been proposed; thus, higher levels of vitamin D might reduce the risk of migraine. However, the results of related studies have been inconclusive. Methods Seventy healthy individuals and 70 age‐ and sex‐matched migraineurs (34 chronic and 36 episodic migraineurs), diagnosed according to the International Headache Society criteria (ICHD‐IIIβ), were recruited. After obtaining baseline data and assessing migraine disability, a 30‐day headache diary was given to the participants. Blood samples were obtained and 25(OH)D serum concentrations were determined using ELISA techniques. Serum 25(OH)D under 20, 20–29, and 30–100 ng/mL were considered deficient, insufficient, and sufficient, respectively. The applied statistical tests for between‐group comparisons include independent‐sample t‐test, chi‐square, and analysis of variance. Multiple regression analysis was also performed to identify the possible risk factors of migraine headache. Results Migraine patients had significantly lower mean (SD) of serum VitD (30 (16) ng/mL) than healthy subjects (43 (19) ng/mL) (P < .001). The number (%) of subjects with VitD deficiency and insufficiency was significantly higher among the migraineurs (36 (53.7%)) than the controls (18 (26.1%)) (P < .0001). A significant negative association between migraine headache and serum VitD was detected in the fully adjusted multiple regression models when comparing the third and the highest serum 25(OH)D quartiles with the lowest (OR = 0.20; 95% CI = 0.05–0.77; OR = 0.17; 95% CI = 0.04–0.64, respectively, P for trend = .009). For each 5 ng/mL increase in serum 25(OH)D, there was a 22% odds decrease in the odds of migraine (OR = 0.78; 95% CI = 0.68–0.90; P = .001). Conclusion We have found that a higher level of serum VitD (between 50 to less than 100 ng/mL) among a sample of the Iranian population is associated with 80–83% lower odds of migraine headache than those with serum 25(OH)D levels below 20 ng/mL. However, there is a need for well‐designed clinical trials to investigate beneficial effects of increased serum 25(OH)D on lower risk of migraine.

show abstract

Section: Discussionmentioning

confidence: 99%

Serum Vitamin D Status in a Group of Migraine Patients Compared With Healthy Controls: A Case–Control Study

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Despite its severity and prevalence, migraine is still poorly understood, underscoring a clear unmet therapeutic need for many patients. The gold standard of acute migraine therapy remains oral triptan treatment; however, its use is limited by its propensity to induce medication-overuse headache with frequent use and rare but potentially serious cardiovascular and cerebrovascular adverse events (Loder, 2010;Russo, 2015;Obermann and Holle, 2016;Lukacs et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…PACAP is a multifunctional neuropeptide that has been implicated in migraine pathophysiology (reviewed by Schytz et al, 2010b;Kaiser and Russo, 2013;Lukacs et al, 2017;Vollesen and Ashina, 2017;Rubio-Beltrán et al, 2018). PACAP is a member of the secretin/vasoactive intestinal peptide (VIP)/ growth hormone-releasing hormone family and exists in two a-amidated active forms, one composed of 38 amino acids and a second composed of 27 amino acids (PACAP38 and PACAP27, respectively) (Miyata et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Pharmacologic Characterization of ALD1910, a Potent Humanized Monoclonal Antibody against the Pituitary Adenylate Cyclase-Activating Peptide

Loomis

Dutzar

Ojala

et al. 2019

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Migraine is a debilitating disease that affects almost 15% of the population worldwide and is the first cause of disability in people under 50 years of age, yet its etiology and pathophysiology remain incompletely understood. Recently, small molecules and therapeutic antibodies that block the calcitonin gene-related peptide (CGRP) signaling pathway have reduced migraine occurrence and aborted acute attacks of migraine in clinical trials and provided prevention in patients with episodic and chronic migraine. Heterogeneity is present within each diagnosis and patient's response to treatment, suggesting migraine as a final common pathway potentially activated by multiple mechanisms, e.g., not all migraine attacks respond to or are prevented by anti-CGRP pharmacological interventions. Consequently, other unique mechanisms central to migraine pathogenesis may present new targets for drug development. Pituitary adenylate cyclase-activating peptide (PACAP) is an attractive novel target for treatment of migraines. We generated a specific, high-affinity, neutralizing monoclonal antibody (ALD1910) with reactivity to both PACAP38 and PACAP27. In vitro, ALD1910 effectively antagonizes PACAP38 signaling through the pituitary adenylate cyclase-activating peptide type I receptor, vasoactive intestinal peptide receptor 1, and vasoactive intestinal peptide receptor 2. ALD1910 recognizes a nonlinear epitope within PACAP and blocks its binding to the cell surface. To test ALD1910 antagonistic properties directed against endogenous PACAP, we developed an umbellulone-induced rat model of neurogenic vasodilation and parasympathetic lacrimation. In vivo, this model demonstrates that the antagonistic activity of ALD1910 is dosedependent, retaining efficacy at doses as low as 0.3 mg/kg. These results indicate that ALD1910 represents a potential therapeutic antibody to address PACAP-mediated migraine.

show abstract

“…There are two potential explanations: 1. the two amids act peripherally, metabolized only in small proportion two KYNA, 2. the pharmacokinetic studies were performed in intact animals. In case of neurogenic inflammation, an important phenomenon that occurs during trigeminovascular activation causes BBB dysfunction, where the BBB becomes penetrable for substances that are normally unable to pass [17,168]. We assume that during migraine attack the BBB dysfunction occurs and penetrance of KYNA analogues might be possible but future studies are needed to test this hypothesis.…”

Section: Kynurenic Acid (Kyna)mentioning

confidence: 99%

“…The studies concluded that any future therapeutic approach related to NO. synthesis should be handled with dubitation [168].…”

Section: Nitric Oxide (No)mentioning

confidence: 99%

The Therapeutic Impact of New Migraine Discoveries

Vécsei

Lukács

Tajti

et al. 2019

CMC

Self Cite

View full text Add to dashboard Cite

show abstract

Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects

Cited by 48 publications

References 134 publications

Serum Vitamin D Status in a Group of Migraine Patients Compared With Healthy Controls: A Case–Control Study

Serum Vitamin D Status in a Group of Migraine Patients Compared With Healthy Controls: A Case–Control Study

Pharmacologic Characterization of ALD1910, a Potent Humanized Monoclonal Antibody against the Pituitary Adenylate Cyclase-Activating Peptide

The Therapeutic Impact of New Migraine Discoveries

Contact Info

Product

Resources

About