The Therapeutic Impact of New Migraine Discoveries

2019 ◽  
Vol 26 (34) ◽  
pp. 6261-6281 ◽  
Author(s):  
László Vécsei ◽  
Melinda Lukács ◽  
János Tajti ◽  
Ferenc Fülöp ◽  
József Toldi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Preventive Treatment ◽  
Therapeutic Strategies ◽  
Migraine Treatment ◽  
Preclinical Studies ◽  
Therapeutic Approaches ◽  
Trigeminovascular System ◽  
Glutamate Receptor Antagonists

Background: Migraine is one of the most disabling neurological conditions and associated with high socio-economic costs. Though certain aspects of the pathomechanism of migraine are still incompletely understood, the leading hypothesis implicates the role of the activation of the trigeminovascular system. Triptans are considered to be the current gold standard therapy for migraine attacks; however, their use in clinical practice is limited. Prophylactic treatment includes non-specific approaches for migraine prevention. All these support the need for future studies in order to develop innovative anti-migraine drugs. Objective: The present study is a review of the current literature regarding new therapeutic lines in migraine research. Methods: A systematic literature search in the database of PUBMED was conducted concerning therapeutic strategies in a migraine published until July 2017. Results: Ongoing clinical trials with 5-HT1F receptor agonists and glutamate receptor antagonists offer promising new aspects for acute migraine treatment. Monoclonal antibodies against CGRP and the CGRP receptor are revolutionary in preventive treatment; however, further long-term studies are needed to test their tolerability. Preclinical studies show positive results with PACAP- and kynurenic acid-related treatments. Other promising therapeutic strategies (such as those targeting TRPV1, substance P, NOS, or orexin) have failed to show efficacy in clinical trials. Conclusion: Due to their side-effects, current therapeutic approaches are not suitable for all migraine patients. Especially frequent episodic and chronic migraine represents a therapeutic challenge for researchers. Clinical and preclinical studies are needed to untangle the pathophysiology of migraine in order to develop new and migraine-specific therapies.

scholarly journals Immune Check-Point Inhibitors and Standard Chemoradiotherapy in Definitive Head and Neck Cancer Treatment

2021 ◽  
Vol 11 (5) ◽  
pp. 393
Author(s):  
Francesca De Felice ◽  
Daniela Musio ◽  
Vincenzo Tombolini
Keyword(s):  
Clinical Trials ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Therapeutic Strategies ◽  
Check Point ◽  
Clinical Tool ◽  
Cancer Management ◽  
Check Point Inhibitors

In head and neck cancer management, there is a need for tailored approaches to optimally implement clinical outcomes. Based on the assumption that efficacy and long-term toxicity are not satisfactory for standard concurrent platinum-based chemoradiotherapy, several trials have been designed to test whether induction immunotherapy and/or concomitant immunotherapy and radiotherapy result in improved survival and toxicity outcomes. Here, we present an overview of the most recent concomitant therapeutic strategies for head and neck cancer, focusing on the knowledge available regarding check-point inhibitors. The aim is to present the characteristics of the main check-point inhibitors and to summarize the clinical trials on the combination of immune check-point inhibitors and (chemo)radiotherapy in the definitive HNC setting, in order to provide a useful clinical tool for further research.

scholarly journals New Insights into Molecular Oncogenesis and Therapy of Uveal Melanoma

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 694 ◽  
Author(s):  
Sara Silvia Violanti ◽  
Ilaria Bononi ◽  
Carla Enrica Gallenga ◽  
Fernanda Martini ◽  
Mauro Tognon ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Target Genes ◽  
Therapeutic Strategies ◽  
Biomedical Sciences ◽  
Therapeutic Approaches ◽  
Common Cancer ◽  
Multistep Process ◽  
Systemic Adjuvant Therapy ◽  
Novel Therapeutic

Uveal melanoma (UM), which is the most common cancer of the eye, was investigated in recent years by many teams in the field of biomedical sciences and eye clinicians. New knowledge was acquired on molecular pathways found to be dysregulated during the multistep process of oncogenesis, whereas novel therapeutic approaches gave significant results in the clinical applications. Uveal melanoma-affected patients greatly benefited from recent advances of the research in this eye cancer. Tumour biology, genetics, epigenetics and immunology contributed significantly in elucidating the role of different genes and related pathways during uveal melanoma onset/progression and UM treatments. Indeed, these investigations allowed identification of new target genes and to develop new therapeutic strategies/compounds to cure this aggressive melanoma of the eye. Unfortunately, the advances reported in the treatment of cutaneous melanoma have not produced analogous benefits in metastatic uveal melanoma. Nowadays, no systemic adjuvant therapy has been shown to improve overall survival or reduce the risk of metastasis. However, the increasing knowledge of this disease, and the encouraging results seen in clinical trials, offer promise for future effective therapies. Herein, different pathways/genes involved in uveal melanoma onset/progression were taken into consideration, together with novel therapeutic approaches.

scholarly journals Autophagy Intertwines with Different Diseases—Recent Strategies for Therapeutic Approaches

Diseases ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 15 ◽  
Author(s):  
Janani Ramesh ◽  
Larance Ronsard ◽  
Anthony Gao ◽  
Bhuvarahamurthy Venugopal
Keyword(s):  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Open Reading Frames ◽  
Signaling Cascades ◽  
Progression Rate ◽  
Therapeutic Approaches ◽  
Genes Encoding ◽  
Novel Therapeutic Strategies ◽  
Reading Frames

Autophagy is a regular and substantial “clear-out process” that occurs within the cell and that gets rid of debris that accumulates in membrane-enclosed vacuoles by using enzyme-rich lysosomes, which are filled with acids that degrade the contents of the vacuoles. This machinery is well-connected with many prevalent diseases, including cancer, HIV, and Parkinson’s disease. Considering that autophagy is well-known for its significant connections with a number of well-known fatal diseases, a thorough knowledge of the current findings in the field is essential in developing therapies to control the progression rate of diseases. Thus, this review summarizes the critical events comprising autophagy in the cellular system and the significance of its key molecules in manifesting this pathway in various diseases for down- or upregulation. We collectively reviewed the role of autophagy in various diseases, mainly neurodegenerative diseases, cancer, inflammatory diseases, and renal disorders. Here, some collective reports on autophagy showed that this process might serve as a dual performer: either protector or contributor to certain diseases. The aim of this review is to help researchers to understand the role of autophagy-regulating genes encoding functional open reading frames (ORFs) and its connection with diseases, which will eventually drive better understanding of both the progression and suppression of different diseases at various stages. This review also focuses on certain novel therapeutic strategies which have been published in the recent years based on targeting autophagy key proteins and its interconnecting signaling cascades.

Controversies on neuroprotection therapy in non-arteritic anterior ischaemic optic neuropathy

2019 ◽  
Vol 104 (2) ◽  
pp. 153-156
Author(s):  
Sohan Singh Hayreh
Keyword(s):  
Clinical Trials ◽  
Ischaemic Stroke ◽  
Optic Neuropathy ◽  
Experimental Studies ◽  
Therapeutic Strategies ◽  
Ischaemic Optic Neuropathy ◽  
Pubmed Search ◽  
Anterior Ischaemic Optic Neuropathy ◽  
Study Designs

ObjectiveThere has long been a great interest in neuroprotection therapy for ischaemic stroke and various types of optic neuropathies. In view of that, I reviewed the literature on the role of neuroprotection for non-arteritic anterior ischaemic optic neuropathy (NA-AION).MethodsThe review is based on a PubMed search of literature about the use of neuroprotectors in stroke and optic neuropathies and about current clinical trials of RPh201 and QPI-1007 in NA-AION.ResultsSeveral neuroprotection agents for ischaemic stroke and various types of optic neuropathies have been evaluated extensively in experimental studies in animals and benefits claimed. However, translation of therapeutic strategies for neuroprotection from experimental research to humans has invariably been fraught with failure. Two currently ongoing studies dealing with neuroprotection by RPh201 and QPI-1007 in NA-AION may have limitations in their rationale and study designs.ConclusionsUnfortunately, in spite of all the experimental and clinical research on neuroprotection agents in NA-AION so far, we have no scientifically proven evidence of neuroprotection agents showing any benefit in the human clinical studies so far.

scholarly journals How I manage ibrutinib intolerance and complications in patients with chronic lymphocytic leukemia

Blood ◽  
2019 ◽  
Vol 133 (12) ◽  
pp. 1298-1307 ◽  
Author(s):  
Deborah M. Stephens ◽  
John C. Byrd
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Chronic Lymphocytic Leukemia ◽  
Adverse Events ◽  
Real World ◽  
Lymphocytic Leukemia ◽  
Targeted Therapeutics ◽  
Therapeutic Approaches ◽  
Therapeutic Alternatives

Abstract Chronic lymphocytic leukemia (CLL) therapy has changed dramatically with the introduction of several targeted therapeutics. Ibrutinib was the first approved for use in 2014 and now is used for initial and salvage therapy of CLL patients. With its widespread use in clinical practice, ibrutinib’s common and uncommon adverse events reported less frequently in earlier clinical trials have been experienced more frequently in real-world practice. In particular, atrial fibrillation, bleeding, infections, and arthralgias have been reported. The management of ibrutinib’s adverse events often cannot be generalized but must be individualized to the patient and their long-term risk of additional complications. When ibrutinib was initially developed, there were limited therapeutic alternatives for CLL, which often resulted in treating through the adverse events. At the present time, there are several effective alternative agents available, so transition to an alternative CLL directed therapy may be considered. Given the continued expansion of ibrutinib across many therapeutic areas, investigation of the pathogenesis of adverse events with this agent and also clinical trials examining therapeutic approaches for complications arising during therapy are needed. Herein, we provide strategies we use in real-world CLL clinical practice to address common adverse events associated with ibrutinib.

scholarly journals The Role of Animal Models in Evaluating Reasonable Safety and Efficacy for Human Trials of Cell-Based Interventions for Neurologic Conditions

2008 ◽  
Vol 29 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Alan Regenberg ◽  
Debra JH Mathews ◽  
David M Blass ◽  
Hilary Bok ◽  
Joseph T Coyle ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Regenerative Medicine ◽  
Therapeutic Agents ◽  
Preclinical Studies ◽  
Safety And Efficacy ◽  
Proper Role ◽  
New Treatments ◽  
Gathering Data

Progress in regenerative medicine seems likely to produce new treatments for neurologic conditions that use human cells as therapeutic agents; at least one trial for such an intervention is already under way. The development of cell-based interventions for neurologic conditions (CBI-NCs) will likely include preclinical studies using animals as models for humans with conditions of interest. This paper explores predictive validity challenges and the proper role for animal models in developing CBI-NCs. In spite of limitations, animal models are and will remain an essential tool for gathering data in advance of first-in-human clinical trials. The goal of this paper is to provide a realistic lens for viewing the role of animal models in the context of CBI-NCs and to provide recommendations for moving forward through this challenging terrain.

Clinical Trials in Recurrent Ovarian Cancer

2011 ◽  
Vol 21 (4) ◽  
pp. 771-775 ◽  
Author(s):  
Michael Friedlander ◽  
Edward Trimble ◽  
Anna Tinker ◽  
David Alberts ◽  
Elisabeth Avall-Lundqvist ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Gynecologic Cancer ◽  
Recurrent Ovarian Cancer ◽  
Consensus Conference ◽  
Ca 125 ◽  
Therapeutic Approaches ◽  
Cooperative Research ◽  
International Consensus

The 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup was held in Vancouver, Canada, in June 2010. Representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. Group C, 1 of the 3 discussion groups, examined recurrent ovarian cancer, and we report the consensus reached regarding 4 questions. These included the following: (1) What is the role of cytoreductive surgery for recurrent ovarian cancer? (2) How do we define distinct patient populations in need of specific therapeutic approaches? (3) Should end points for trials with recurrent disease vary from those of first-line trials? (4) Is CA-125 progression alone sufficient for entry/eligibility into clinical trials?

scholarly journals The Role of Simulation Modeling in Planning Long-Term Clinical Trials in Type 2 Diabetes

2013 ◽  
Vol 16 (7) ◽  
pp. A587-A588
Author(s):  
V. Foos ◽  
D. Grant ◽  
J.L. Palmer ◽  
M. Lamotte ◽  
P. McEwan
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trials ◽  
Simulation Modeling

scholarly journals Potential Therapeutic Strategies for Alzheimer’s Disease Targeting or Beyondβ-Amyloid: Insights from Clinical Trials

2014 ◽  
Vol 2014 ◽  
pp. 1-22 ◽  
Author(s):  
Qiutian Jia ◽  
Yulin Deng ◽  
Hong Qing
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Drug Targets ◽  
Neurodegenerative Disorder ◽  
Therapeutic Strategies ◽  
Therapeutic Approaches ◽  
Drug Candidates ◽  
Effective Drugs ◽  
Novel Drug

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with two hallmarks:β-amyloid plagues and neurofibrillary tangles. It is one of the most alarming illnesses to elderly people. No effective drugs and therapies have been developed, while mechanism-based explorations of therapeutic approaches have been intensively investigated. Outcomes of clinical trials suggested several pitfalls in the choice of biomarkers, development of drug candidates, and interaction of drug-targeted molecules; however, they also aroused concerns on the potential deficiency in our understanding of pathogenesis of AD, and ultimately stimulated the advent of novel drug targets tests. The anticipated increase of AD patients in next few decades makes development of better therapy an urgent issue. Here we attempt to summarize and compare putative therapeutic strategies that have completed clinical trials or are currently being tested from various perspectives to provide insights for treatments of Alzheimer’s disease.

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