Monoclonal Antibodies as Neurological Therapeutics

Gklinos, Panagiotis; Papadopoulou, Miranta; Stanulović, Vid; Mitsikostas, Dimos D.; Papadopoulos, Dimitrios

doi:10.3390/ph14020092

Cited by 40 publications

(25 citation statements)

References 247 publications

(295 reference statements)

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“…While further studies explore the role of the blockers of these channels, the story of monoclonal antibodies (mAbs) directed towards CGRP (eptinezumab, fremanezumab, and galcanezumab) and its canonical receptor (erenumab) has not come to an end and therapeutic innovation can be anticipated. In fact, mAbs have revolutionized the therapy of several neurologic diseases, acting through direct mechanisms in the case of migraine [ 44 ]. The presence of CGRP immunoreactive fibres around cerebral vessels originating from the trigeminal ganglion has been demonstrated ( Figure 2 ) shedding light on the neurogenic activities exerted by the trigemino-cerebrovascular system [ 45 ].…”

Section: Novel Perspectives and Future Directions: Focus On Eptinezumabmentioning

confidence: 99%

Progress in the Treatment of Migraine Attacks: From Traditional Approaches to Eptinezumab

Scuteri

Bagetta

2021

Pharmaceuticals

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Migraine is the second cause of disability and of lost years of healthy life worldwide. Migraine is characterized by recurrent headache attacks and accompanying disabling symptoms lasting 4–48 h. In episodic migraine, attacks occur in less than 15 days per month and in chronic migraine, in more than 15 monthly days. Whilst successful translation of pharmacological discoveries into efficacious therapeutics has been achieved in the preventative therapy of chronic migraine, treatment of acute migraine suffers the lack of effective advancements. An effective treatment affords complete freedom from pain two hours after therapy and provides the absence of the most bothersome symptom (MBS) associated with migraine after 2 h. However, available anti-migraine abortive treatments for acute attacks do not represent an effective and safe treatment for all the populations treated. In particular, the most used specific treatment is represented by triptans that offer 2-h sustained freedom from pain achieved in 18–50% of patients but they are contraindicated in coronary artery disease, stroke and peripheral vascular disease due to the vasoconstriction at the basis of their pharmacologic action. The most novel therapies, i.e., gepants and ditans, are without sufficient post-marketing data for secure use. Here, an attempt is proposed to analyse the rational basis and evidence in favour of investigating the efficacy and safety in acute migraine attacks of eptinezumab, i.e., monoclonal antibody (mAb) directed towards calcitonin gene-related peptide (CGRP) unique for intravenous infusion administration.

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Section: Novel Perspectives and Future Directions: Focus On Eptinezumabmentioning

confidence: 99%

Progress in the Treatment of Migraine Attacks: From Traditional Approaches to Eptinezumab

Scuteri

Bagetta

2021

Pharmaceuticals

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“…The rationale for nanotheranostics in the treatment of neurological disease by crossing the BBB upon systemic administration is underpinned by the limitations of conventional empirical therapy [39]. Despite numerous advances in this field, particularly in relation to biotechnology and the revolution of monoclonal antibodies and immunotherapies, such therapeutics have hardly increased the delivery efficiency, nor significantly ameliorated the competence of current clinical diagnostics and chemotherapeutic regimens in particular [40,41]. One of the primary attributes of maladies of the brain is that prompt primary diagnosis treatment that is tailored to the patient is at a premium.…”

Section: Rationale For Nanotheranostics Over Standard Therapiesmentioning

confidence: 99%

Advances in Non-Animal Testing Approaches towards Accelerated Clinical Translation of Novel Nanotheranostic Therapeutics for Central Nervous System Disorders

Lynch

Gobbo

2021

Nanomaterials

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Nanotheranostics constitute a novel drug delivery system approach to improving systemic, brain-targeted delivery of diagnostic imaging agents and pharmacological moieties in one rational carrier platform. While there have been notable successes in this field, currently, the clinical translation of such delivery systems for the treatment of neurological disorders has been limited by the inadequacy of correlating in vitro and in vivo data on blood–brain barrier (BBB) permeation and biocompatibility of nanomaterials. This review aims to identify the most contemporary non-invasive approaches for BBB crossing using nanotheranostics as a novel drug delivery strategy and current non-animal-based models for assessing the safety and efficiency of such formulations. This review will also address current and future directions of select in vitro models for reducing the cumbersome and laborious mandate for testing exclusively in animals. It is hoped these non-animal-based modelling approaches will facilitate researchers in optimising promising multifunctional nanocarriers with a view to accelerating clinical testing and authorisation applications. By rational design and appropriate selection of characterised and validated models, ranging from monolayer cell cultures to organ-on-chip microfluidics, promising nanotheranostic particles with modular and rational design can be screened in high-throughput models with robust predictive power. Thus, this article serves to highlight abbreviated research and development possibilities with clinical translational relevance for developing novel nanomaterial-based neuropharmaceuticals for therapy in CNS disorders. By generating predictive data for prospective nanomedicines using validated in vitro models for supporting clinical applications in lieu of requiring extensive use of in vivo animal models that have notable limitations, it is hoped that there will be a burgeoning in the nanotherapy of CNS disorders by virtue of accelerated lead identification through screening, optimisation through rational design for brain-targeted delivery across the BBB and clinical testing and approval using fewer animals. Additionally, by using models with tissue of human origin, reproducible therapeutically relevant nanomedicine delivery and individualised therapy can be realised.

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“…IgG2 and IgG4 exhibit a lower affinity to the Fcγ receptor and are preferred for blocking antigen function. More specifically, both subclasses are preferred when aiming to neutralize the soluble antigen without inducing the host effector mechanisms [42]. Finally, special attention should be given to the fact that galcanezumab is the only one among the four currently approved mAbs, which has also been approved for the prevention of cluster headache [43].…”

Section: Galcanezumab and Other Mabs In Migraine Prophylaxismentioning

confidence: 99%

The Role of Galcanezumab in Migraine Prevention: Existing Data and Future Directions

Gklinos

Mitsikostas

2021

Pharmaceuticals

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Galcanezumab is a humanized monoclonal antibody blocking the calcitonin gene-related peptide (CGRP) pathway by targeting the CGRP. Data from four phase-3 randomized placebo-controlled clinical trials showed that galcanezumab is superior to placebo in reducing migraine headaches, migraine-specific quality of life, and headache-related disability. Most of the adverse events (AEs) were mild to moderate and did not affect trial completion rates significantly. Along with erenumab, fremanezumab, and eptinezumab, galcanezumab forms a novel class of anti-migraine preventative treatments that is disease-specific and mechanism-based, unlike the standard ones. In addition, galcanezumab has also been shown to be effective in cluster headache, though more clinical trials are required. Overall, galcanezumab is a promising emerging treatment in migraine prophylaxis. However, it needs to be tested in larger clinical trials focused on treatment-resistant migraine. Furthermore, its safety profile, especially its potential association with an increased cardiovascular risk, needs to be established through long-term, real-world data. This review aims to give an overview of its pharmacological properties as well as to report and discuss data from clinical trials and its potential place in headache therapeutics.

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Monoclonal Antibodies as Neurological Therapeutics

Cited by 40 publications

References 247 publications

Progress in the Treatment of Migraine Attacks: From Traditional Approaches to Eptinezumab

Progress in the Treatment of Migraine Attacks: From Traditional Approaches to Eptinezumab

Advances in Non-Animal Testing Approaches towards Accelerated Clinical Translation of Novel Nanotheranostic Therapeutics for Central Nervous System Disorders

The Role of Galcanezumab in Migraine Prevention: Existing Data and Future Directions

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