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.

scholarly journals Inflammation and Atherosclerosis

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1197
Author(s):  
Klaus Ley
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Basic Science ◽  
Translational Science ◽  
Special Issue

This 11-chapter Special Issue of Cells spans the gamut from basic science in mechanistic animal models to translational science to outcomes of clinical trials, all focused on the role of inflammation in atherosclerosis [...]

scholarly journals Using magnetic resonance imaging in animal models to guide drug development in multiple sclerosis

2013 ◽  
Vol 20 (1) ◽  
pp. 3-11 ◽  
Author(s):  
Nabeela Nathoo ◽  
V Wee Yong ◽  
Jeff F Dunn
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Magnetic Resonance ◽  
Animal Models ◽  
Mr Imaging ◽  
Preclinical Studies ◽  
Resonance Imaging ◽  
Magnetic Resonance Imaging Mri ◽  
Potential Therapeutics

Major advances are taking place in the development of therapeutics for multiple sclerosis (MS), with a move past traditional immunomodulatory/immunosuppressive therapies toward medications aimed at promoting remyelination or neuroprotection. With an increase in diversity of MS therapies comes the need to assess the effectiveness of such therapies. Magnetic resonance imaging (MRI) is one of the main tools used to evaluate the effectiveness of MS therapeutics in clinical trials. As all new therapeutics for MS are tested in animal models first, it is logical that MRI be incorporated into preclinical studies assessing therapeutics. Here, we review key papers showing how MR imaging has been combined with a range of animal models to evaluate potential therapeutics for MS. We also advise on how to maximize the potential for incorporating MRI into preclinical studies evaluating possible therapeutics for MS, which should improve the likelihood of discovering new medications for the condition.

scholarly journals A new era for stroke therapy: Integrating neurovascular protection with optimal reperfusion

2018 ◽  
Vol 38 (12) ◽  
pp. 2073-2091 ◽  
Author(s):  
Ligen Shi ◽  
Marcelo Rocha ◽  
Rehana K Leak ◽  
Jingyan Zhao ◽  
Tarun N Bhatia ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Cell Types ◽  
Phase Iii ◽  
Preclinical Studies ◽  
New Era ◽  
Stroke Research ◽  
Neuroprotective Strategies ◽  
Neurovascular Protection ◽  
Phase Iii Trials

Recent advances in stroke reperfusion therapies have led to remarkable improvement in clinical outcomes, but many patients remain severely disabled, due in part to the lack of effective neuroprotective strategies. In this review, we show that 95% of published preclinical studies on “neuroprotectants” (1990–2018) reported positive outcomes in animal models of ischemic stroke, while none translated to successful Phase III trials. There are many complex reasons for this failure in translational research, including that the majority of clinical trials did not test early delivery of neuroprotectants in combination with successful reperfusion. In contrast to the clinical trials, >80% of recent preclinical studies examined the neuroprotectant in animal models of transient ischemia with complete reperfusion. Furthermore, only a small fraction of preclinical studies included long-term functional assessments, aged animals of both genders, and models with stroke comorbidities. Recent clinical trials demonstrate that 70%–80% of patients treated with endovascular thrombectomy achieve successful reperfusion. These successes revive the opportunity to retest previously failed approaches, including cocktail drugs that target multiple injury phases and different cell types. It is our hope that neurovascular protectants can be retested in future stroke research studies with specific criteria outlined in this review to increase translational successes.

scholarly journals Complex Regional Pain Syndrome (CRPS/RSD) and Neuropathic Pain: Role of Intravenous Bisphosphonates as Analgesics

2008 ◽  
Vol 8 ◽  
pp. 229-236 ◽  
Author(s):  
Jennifer Yanow ◽  
Marco Pappagallo ◽  
Letha Pillai
Keyword(s):  
Clinical Trials ◽  
Neuropathic Pain ◽  
Animal Models ◽  
Complex Regional Pain Syndrome ◽  
Bone Pain ◽  
Treatment Options ◽  
Pain Syndrome ◽  
Pain Pathways ◽  
Intravenous Bisphosphonates

Neuropathic pain is a sequela of dysfunction, injuries, or diseases of the peripheral and/or central nervous system pain pathways, which has historically been extremely difficult to treat. Complex regional pain syndrome (CRPS) types 1 and 2 are neuropathic pain conditions that have a long history in the medical literature but whose pathophysiology remains elusive and whose available treatment options remain few. While an exact animal model for CRPS doesn't yet exist, there are several animal models of neuropathic pain that develop behaviors of hypersensitivity, one of the hallmark signs of neuropathic pain in humans.Bisphosphonates have been used for pathologic conditions associated with abnormal bone metabolism, such as osteoporosis, Paget’s disease and cancer-related bone pain for many years. More recently, results of clinical trials have indicated the potential role of bisphosphonates in the treatment of CRPS/RSD.In this paper we will review the preclinical studies regarding the use of bisphosphonates as analgesics in animal models of neuropathic pain, and also summarize the clinical trials that have been done to date. We will give an overview of bisphosphonate pharmacology and discuss several potential mechanisms by which bisphosphonates may be analgesic in CRPS/RSD and bone pain of noncancer origin.

scholarly journals Safety of Mesenchymal Stem Cells for Clinical Application

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Youwei Wang ◽  
Zhi-bo Han ◽  
Yong-ping Song ◽  
Zhong Chao Han
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Therapeutic Agents ◽  
Great Promise ◽  
Safety Issues ◽  
Human Use

Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine and autoimmune diseases, based on their differentiation abilities and immunosuppressive properties. However, the therapeutic applications raise a series of questions about the safety of culture-expanded MSCs for human use. This paper summarized recent findings about safety issues of MSCs, in particular their genetic stability in long-termin vitroexpansion, their cryopreservation, banking, and the role of serum in the preparation of MSCs.

scholarly journals Reinforcement-based cognitive biases as vulnerability factors in alcohol addiction: From humans to animal models

2021 ◽  
Author(s):  
Karolina Noworyta ◽  
Agata Cieslik ◽  
Rafal Rygula
Keyword(s):  
Animal Models ◽  
Cognitive Biases ◽  
Alcohol Addiction ◽  
Vulnerability Factors ◽  
Preclinical Research ◽  
Reinforcement Sensitivity ◽  
Recent Developments ◽  
Psychiatric Conditions ◽  
New Treatments

Alcohol use disorder (AUD) is one of the most common but still poorly treated psychiatric conditions. Developing new treatments requires a better understanding of the aetiology of symptoms and evaluation of novel therapeutic targets in preclinical studies. Recent developments in our understanding of the reinforcement-based cognitive biases (RBCBs) that contribute to the development of AUD and its treatment offer new opportunities for both clinical and preclinical research. In this review, we first briefly describe psychological and cognitive theories that implicate various aspects of reinforcement sensitivity in the development, maintenance, and recurrence of alcohol addiction. Furthermore, in separate sections, we describe studies investigating RBCBs and their neural, neurochemical, and pharmacological correlates, and we discuss possible interactions between RBCBs and trajectories of AUD. Finally, we describe how recent translational studies using state-of-the-art animal models can facilitate our understanding of the role of reinforcement sensitivity and RBCBs in various aspects of AUD.

scholarly journals Mitochondria-Targeted Drugs

2019 ◽  
Vol 12 (3) ◽  
pp. 202-214 ◽  
Author(s):  
Roman A. Zinovkin ◽  
Andrey A. Zamyatnin
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Targeted Drugs ◽  
Molecular Pharmacology ◽  
National Library ◽  
Lipophilic Cations ◽  
Wide Range ◽  
Metabolic Conditions ◽  
Available Information

Background: Targeting of drugs to the subcellular compartments represents one of the modern trends in molecular pharmacology. The approach for targeting mitochondria was developed nearly 50 years ago, but only in the last decade has it started to become widely used for delivering drugs. A number of pathologies are associated with mitochondrial dysfunction, including cardiovascular, neurological, inflammatory and metabolic conditions. Objective: This mini-review aims to highlight the role of mitochondria in pathophysiological conditions and diseases, to classify and summarize our knowledge about targeting mitochondria and to review the most important preclinical and clinical data relating to the antioxidant lipophilic cations MitoQ and SkQ1. Methods: This is a review of available information in the PubMed and Clinical Trials databases (US National Library of Medicine) with no limiting period. Results and Conclusion: Mitochondria play an important role in the pathogenesis of many diseases and possibly in aging. Both MitoQ and SkQ1 have shown many beneficial features in animal models and in a few completed clinical trials. More clinical trials and research efforts are needed to understand the signaling pathways influenced by these compounds. The antioxidant lipophilic cations have great potential for the treatment of a wide range of pathologies.

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.

A Role of Clinical Trial in Management of Hypertension and Medication of Hypertension

2021 ◽  
pp. 3215-3222
Author(s):  
Minesh Patel ◽  
G.S. Chakraborthy
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Clinical Trials ◽  
Left Ventricle ◽  
New Drugs ◽  
Research Review ◽  
Incremental Growth ◽  
Indian Food ◽  
New Treatments

Clinical trials are essence for the progress of new treatments. Whether a person should engage confide in on their compassionate of the liability and gain for themselves and for society as an entity. Clinical trials are research review in which people volunteer to attempt major treatments, interventions or experiment as a means to forbid, detect, evaluate or manage assorted diseases or medical conditions. Some investigations glance at how people react to a new arbitration and what side effects valor occur. Every new medicine and treatment initiated with volunteers engage in clinical trials. We incur our present high ideal of medical care to studies that have been operate in the past under guidance of the INDIAN Food and Drug Administration (FDA). In addition to Research on new drugs and devices, clinical trials bring a scientific footing for urge and treating patients. Even when researchers do not achieve the conclusion they anticipate; trial results can help point scientists in the mend direction. Blood pressure is great because the larger than your blood pressure is, the larger than your risk of health problems in the future. If your blood pressure is higher than it is putting extra ache on your arteries and on your heart. High blood pressure clouts your heart to work higher to pump blood to the comfort of your body. This causes part of your heart (left ventricle) to congeal. A congeal left ventricle high your risk of heart attack, heart failure and sudden cardiac death. Heart failure. The arena for clinical trials of hypertension management is in transition. The stage of mega trials may not be bygone but is assuredly in decline. Incremental growth in the therapies assessable in the face of a high global disease hardship has imply that hypertension researchers have also attract on getting beat efficacy and value from the available treatments through arrangement improvement, combinations, and algorithms. There has been go on amuse in the role of nonpharmacological compute in cure and management of hypertension.

scholarly journals Memory T Cells in Flavivirus Vaccination

Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 73 ◽  
Author(s):  
Guangyu Li ◽  
Cody Teleki ◽  
Tian Wang
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Animal Models ◽  
Yellow Fever ◽  
Protective Immunity ◽  
Memory T Cells ◽  
Host Protection ◽  
Tick Borne Encephalitis ◽  
Flavivirus Infection

Flaviviruses include many medically important viruses, such as Dengue virus (DENV), Japanese encephalitis (JEV), tick-borne encephalitis (TBEV), West Nile (WNV), yellow fever (YFV), and Zika viruses (ZIKV). Currently, there are licensed human vaccines for DENV, JEV, TBEV and YFV, but not for WNV or ZIKV. Memory T cells play a central role in adaptive immunity and are important for host protection during flavivirus infection. In this review, we discuss recent findings from animal models and clinical trials and provide new insights into the role of memory T cells in host protective immunity upon vaccination with the licensed flavivirus vaccines.

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