scholarly journals Inflammatory complications of CGRP monoclonal antibodies: a case series

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jason C. Ray ◽  
Penelope Allen ◽  
Ann Bacsi ◽  
Julian J. Bosco ◽  
Luke Chen ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Molecular Mechanisms ◽  
Case Series ◽  
Preventive Treatment ◽  
The Body ◽  
Temporal Association ◽  
Organ Systems ◽  
Calcitonin Gene ◽  
Close Proximity ◽  
The Central Nervous System

Abstract Background Calcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response. Cases We present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy. Conclusion This case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward.

Early Experiences in Switching between Monoclonal Antibodies in Patients with Nonresponsive Migraine in Spain: A Case Series

2021 ◽  
pp. 1-4
Author(s):  
Ignacio Patier Ruiz ◽  
Javier Sánchez-Rubio Ferrández ◽  
Alba Cárcamo Fonfría ◽  
Teresa Molina García
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Therapeutic Targets ◽  
Case Series ◽  
Similar Efficacy ◽  
Migraine Prophylaxis ◽  
Therapeutic Failure ◽  
Related Peptide ◽  
Early Experiences ◽  
Calcitonin Gene

Monoclonal antibodies targeting the calcitonin gene-related peptide have been introduced into the therapeutic arsenal of migraine prophylaxis. Clinical trials report similar efficacy between them, and there is no evidence of switching to another one after failure. We aim to describe our experience in switching from erenumab to galcanezumab after therapeutic failure. We retrospectively reviewed 30 migraine patients who received monoclonal antibodies, with 15 of them switched after failure to achieve reduction in migraine days per month ≥30%. A ≥30% reduction in migraine days per month compared to baseline was observed in 8/15 (4/15 ≥ 50%) patients after switch. Some nonresponsive patients may benefit from switching between monoclonal antibodies with different therapeutic targets.

scholarly journals A comprehensive review on clinical and mechanistic pathophysiological aspects of COVID-19 Malady: How far have we come?

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Baila Shakaib ◽  
Tanzeel Zohra ◽  
Aamer Ikram ◽  
Muhammad Bin Shakaib ◽  
Amna Ali ◽  
...  
Keyword(s):  
Case Reports ◽  
Case Series ◽  
Signs And Symptoms ◽  
Organ Damage ◽  
Underlying Disease ◽  
The Body ◽  
Host Cells ◽  
Irreversible Damage ◽  
Organ Systems ◽  
Wide Range

AbstractSince its outbreak in 2019, the coronavirus disease (COVID-19) has become a pandemic, affecting more than 52 million people and causing more than 1 million mortalities globally till date. Current research reveals a wide array of disease manifestations and behaviors encompassing multiple organ systems in body and immense systemic inflammation, which have been summarized in this review. Data from a number of scientific reviews, research articles, case series, observational studies, and case reports were retrieved by utilizing online search engines such as Cochrane, PubMed, and Scopus from December 2019 to November 2020. The data for prevalence of signs and symptoms, underlying disease mechanisms and comorbidities were analyzed using SPSS version 25. This review will discuss a wide range of COVID-19 clinical presentations recorded till date, and the current understanding of both the underlying general as well as system specific pathophysiologic, and pathogenetic pathways. These include direct viral penetration into host cells through ACE2 receptors, induction of inflammosomes and immune response through viral proteins, and the initiation of system-wide inflammation and cytokine production. Moreover, peripheral organ damage and underlying comorbid diseases which can lead to short term and long term, reversible and irreversible damage to the body have also been studied. We concluded that underlying comorbidities and their pathological effects on the body contributed immensely and determine the resultant disease severity and mortality of the patients. Presently there is no drug approved for treatment of COVID-19, however multiple vaccines are now in use and research for more is underway.

scholarly journals Minireview: Estrogen Receptor-β: Mechanistic Insights from Recent Studies

2010 ◽  
Vol 24 (9) ◽  
pp. 1703-1714 ◽  
Author(s):  
Bonnie J. Deroo ◽  
Adrian V. Buensuceso
Keyword(s):  
Estrogen Receptor ◽  
Immune System ◽  
Molecular Mechanisms ◽  
The Body ◽  
Estrogen Receptor Β ◽  
Biological Functions ◽  
Significant Progress ◽  
Estrogen Action ◽  
Organ Systems

Abstract The discovery of estrogen receptor-β (ERβ) in 1996 stimulated great interest in the physiological roles and molecular mechanisms of ERβ action. We now know that ERβ plays a major role in mediating estrogen action in several tissues and organ systems, including the ovary, cardiovascular system, brain, and the immune system, and that ERβ and ERα generally play distinct physiological roles in the body. Although significant progress has been made toward understanding the molecular mechanisms of ERβ action, particularly in vitro, there remains a large gap in our understanding of the mechanisms by which ERβ elicits its biological functions in a true physiological context.

scholarly journals Roles of Gasotransmitters in Synaptic Plasticity and Neuropsychiatric Conditions

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Ulfuara Shefa ◽  
Dokyoung Kim ◽  
Min-Sik Kim ◽  
Na Young Jeong ◽  
Junyang Jung
Keyword(s):  
Nervous System ◽  
Synaptic Plasticity ◽  
Neural Plasticity ◽  
Molecular Mechanisms ◽  
Electrical Signal ◽  
The Body ◽  
Major Depressive ◽  
Essential Information ◽  
The Central Nervous System ◽  
Neuropsychiatric Conditions

Synaptic plasticity is important for maintaining normal neuronal activity and proper neuronal functioning in the nervous system. It is crucial for regulating synaptic transmission or electrical signal transduction to neuronal networks, for sharing essential information among neurons, and for maintaining homeostasis in the body. Moreover, changes in synaptic or neural plasticity are associated with many neuropsychiatric conditions, such as schizophrenia (SCZ), bipolar disorder (BP), major depressive disorder (MDD), and Alzheimer’s disease (AD). The improper maintenance of neural plasticity causes incorrect neurotransmitter transmission, which can also cause neuropsychiatric conditions. Gas neurotransmitters (gasotransmitters), such as hydrogen sulfide (H2S), nitric oxide (NO), and carbon monoxide (CO), play roles in maintaining synaptic plasticity and in helping to restore such plasticity in the neuronal architecture in the central nervous system (CNS). Indeed, the upregulation or downregulation of these gasotransmitters may cause neuropsychiatric conditions, and their amelioration may restore synaptic plasticity and proper neuronal functioning and thereby improve such conditions. Understanding the specific molecular mechanisms underpinning these effects can help identify ways to treat these neuropsychiatric conditions.

scholarly journals Calcitonin Gene-Related Peptide Monoclonal Antibodies Versus Botulinum Neurotoxin a in the Preventive Treatment of Chronic Migraine: An Adjusted Indirect Treatment Comparison Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yao-Yao Chen ◽  
Xiao-Qian Ye ◽  
Tai-Chun Tang ◽  
Tian-Wei She ◽  
Min Chen ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Chronic Migraine ◽  
Botulinum Neurotoxin ◽  
Meta Analysis ◽  
Preventive Treatment ◽  
Calcitonin Gene Related Peptide ◽  
Controlled Trials ◽  
Botulinum Neurotoxin A ◽  
Related Peptide ◽  
Calcitonin Gene

Purpose: Calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are new agents approved by the US Food and Drug Administration for preventive treatment of chronic migraine. Comparison between CGRPmAbs and previously approved Botulinum neurotoxin A (BoNT-A) will inform optimal preventive treatment of chronic migraine, but head-to-head trials are lacking. We therefore aimed to perform adjusted indirect comparison between CGRPmAbs and BoNT-A through a meta-analysis.Methods: OVID MEDLINE, EMBASE and the Cochrane central register of controlled trials, clinical registries, and government websites were searched from inception to September 2019. Randomized controlled trials comparing CGRPmAbs or BoNT-A with placebo in the preventive treatment of chronic migraine were included. The primary outcomes were headache days and migraine days measured at week 12. Data were synthesized by using a frequentist approach; and the treatments were ranked by P-score.Results: We included 10 trials (n = 4,678) after screening 1049 candidates. Six trials were with low risk of bias. Fremanezumab had an effect similar to BoNT-A in the reduction of headache days at week 12 (standard mean difference [SMD] 0.08, 95%CI -0.55 to -0.7). Galcanezumab reduced more migraine days than BoNT-A at week 12 (SMD, -0.94, 95%CI −1.24 to −0.63); fremanezumab showed similar findings (SMD, −0.55, 95%CI −0.85 to −0.24). Galcanezumab and fremanezumab had better effect in mitigating headache impact at week 12. CGRPmAbs and BoNT-A had similar adverse event rate.Conclusion: CGRPmAbs and BoNT-A had similar effect in the preventive treatment of chronic migraine. BoNT-A might be preferentially selected owing to its cost-effectiveness profiles. Further studies with direct comparison of the two treatments are warranted.

Organ system effects and reinfection of COVID-19: A systematic review

2021 ◽  
Vol 9 (1) ◽  
pp. 6-6
Author(s):  
Inderbir Padda ◽  
Nimrat Khehra ◽  
Urooj Jaferi ◽  
Dina Mosabbeh ◽  
Harshan Atwal ◽  
...  
Keyword(s):  
Case Reports ◽  
Meta Analysis ◽  
Case Series ◽  
Kidney Injury ◽  
Multiple Organ ◽  
Organ System ◽  
Fulminant Myocarditis ◽  
Preventative Measures ◽  
Organ Systems ◽  
The Central Nervous System

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its effects on the organ systems have been summarized in recent literature with predominant pulmonary characteristics as a hallmark of the COVID-19 virus. Considering its accelerated appearance from Wuhan, China, in December 2019, extrapulmonary effects have been reported globally of SARS-CoV-2 involving the central nervous system (CNS), cardiovascular, gastrointestinal, renal, and hematologic systems; thus, the potential mechanisms, pathophysiology, clinical characteristics, management, outcome, and case reports per organ system are summarized in depth. The authors interpreted articles composed of case reports, case-series, meta-analysis, cohort studies, retrospective studies, and narrative reviews focusing on COVID-19 confirmed cases and their effects on the organ systems. Prevalent clinical organ system complexities include pneumonia, acute respiratory distress syndrome (ARDS), pulmonary hypertension, pulmonary embolism, hypertension, cardiac arrhythmias, myocarditis progressing to fulminant myocarditis, anorexia, nausea, vomiting, diarrhea, liver dysfunction, encephalopathy, encephalitis, meningitis, intracerebral hemorrhage, acute kidney injury, and hypercoagulability causing stroke and disseminated intravascular coagulation (DIC). This comprehensive literature review article will help clinicians and researchers gain insight about SARS-CoV-2 and its diverse effects on multiple organ systems involved, therefore help implement prospective management and preventative measures.

scholarly journals Current Challenges in Understanding the Cellular and Molecular Mechanisms in Niemann–Pick Disease Type C1

2019 ◽  
Vol 20 (18) ◽  
pp. 4392 ◽  
Author(s):  
Anja U. Bräuer ◽  
Angela Kuhla ◽  
Carsten Holzmann ◽  
Andreas Wree ◽  
Martin Witt
Keyword(s):  
Rare Diseases ◽  
Molecular Mechanisms ◽  
Disease Type ◽  
The Body ◽  
Niemann Pick Disease ◽  
Organ Systems ◽  
Causal Therapy ◽  
Niemann Pick ◽  
The Impact ◽  
Pick Disease

Rare diseases are a heterogeneous group of very different clinical syndromes. Their most common causes are defects in the hereditary material, and they can therefore be passed on to descendants. Rare diseases become manifest in almost all organs and often have a systemic expressivity, i.e., they affect several organs simultaneously. An effective causal therapy is often not available and can only be developed when the underlying causes of the disease are understood. In this review, we focus on Niemann–Pick disease type C1 (NPC1), which is a rare lipid-storage disorder. Lipids, in particular phospholipids, are a major component of the cell membrane and play important roles in cellular functions, such as extracellular receptor signaling, intracellular second messengers and cellular pressure regulation. An excessive storage of fats, as seen in NPC1, can cause permanent damage to cells and tissues in the brain and peripheral nervous system, but also in other parts of the body. Here, we summarize the impact of NPC1 pathology on several organ systems, as revealed in experimental animal models and humans, and give an overview of current available treatment options.

CGRP ligand and receptor monoclonal antibodies for migraine prevention: Evidence review and clinical implications

Cephalalgia ◽  
2019 ◽  
Vol 39 (3) ◽  
pp. 445-458 ◽  
Author(s):  
David W Dodick
Keyword(s):  
Monoclonal Antibodies ◽  
Preventive Treatment ◽  
Calcitonin Gene Related Peptide ◽  
Long Term Outcomes ◽  
Open Label ◽  
Peptide Receptor ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Open Label Extension

Background: Monoclonal antibodies that target calcitonin gene-related peptide or the canonical calcitonin gene-related peptide receptor have emerged as effective and well tolerated for the preventive treatment of migraine. These large molecules appear ideally suited for migraine prevention. They have an extended biological half-life, are administered either monthly or quarterly either by subcutaneous injection or intravenous infusion, require minimal or no dose-titration and have the potential for a rapid onset of effect compared to conventional oral preventive drugs. There is high selectivity and they target an important mediator in the pathogenesis of migraine. Investigation: Phase II and pivotal phase III studies have all yielded positive results with a favorable adverse event profile. No serious treatment-related adverse outcomes have thus far been reported in controlled or long-term open-label extension studies. This tolerability profile promises to improve adherence and, possibly, long-term outcomes. Conclusions: Calcitonin gene-related peptide monoclonal antibodies are effective and well tolerated for the preventive treatment of migraine. They have distinct advantages over currently available oral preventive drugs. While treatment-related serious adverse events have not been observed in open-label extension studies, long-term outcomes and safety will require broad exposure in heterogeneous patient populations in clinical practice. In addition, their safety in women, especially during pregnancy, will require longitudinal surveillance. Given the overlapping mechanism(s), the effectiveness of existing (triptans) and emerging (calcitonin gene-related peptide receptor antagonists) acute therapies in those using a calcitonin gene-related peptide mAb will require further study.

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