The challenge and promise of anti-epileptic therapy development in animal models

ABSTRACT Select agents (SA) pose unique challenges for licensing vaccines and therapies. In the case of toxin-mediated diseases, HHS assigns guidelines for SA use, oversees vaccine and therapy development, and approves animal models and approaches to identify mechanisms for toxin neutralization. In this commentary, we discuss next-generation vaccines and therapies against ricin toxin and botulinum toxin, which are regulated SA toxins that utilize structure-based approaches for countermeasures to guide rapid response to future biothreats.

Download Full-text

Pathophysiological Aspects of Alcohol Metabolism in the Liver

International Journal of Molecular Sciences ◽

10.3390/ijms22115717 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5717

Author(s):

Jeongeun Hyun ◽

Jinsol Han ◽

Chanbin Lee ◽

Myunghee Yoon ◽

Youngmi Jung

Keyword(s):

Lipid Metabolism ◽

Liver Disease ◽

Animal Models ◽

Alcohol Intake ◽

Molecular Mechanisms ◽

Alcohol Metabolism ◽

Inflammatory Reactions ◽

Novel Treatments ◽

Major Organ ◽

Therapy Development

Alcoholic liver disease (ALD) is a globally prevalent chronic liver disease caused by chronic or binge consumption of alcohol. The liver is the major organ that metabolizes alcohol; therefore, it is particularly sensitive to alcohol intake. Metabolites and byproducts generated during alcohol metabolism cause liver damage, leading to ALD via several mechanisms, such as impairing lipid metabolism, intensifying inflammatory reactions, and inducing fibrosis. Despite the severity of ALD, the development of novel treatments has been hampered by the lack of animal models that fully mimic human ALD. To overcome the current limitations of ALD studies and therapy development, it is necessary to understand the molecular mechanisms underlying alcohol-induced liver injury. Hence, to provide insights into the progression of ALD, this review examines previous studies conducted on alcohol metabolism in the liver. There is a particular focus on the occurrence of ALD caused by hepatotoxicity originating from alcohol metabolism.

Download Full-text

Epilepsy therapy development: Technical and methodologic issues in studies with animal models

Epilepsia ◽

10.1111/epi.12295 ◽

2013 ◽

Vol 54 ◽

pp. 13-23 ◽

Cited By ~ 39

Author(s):

Aristea S. Galanopoulou ◽

Merab Kokaia ◽

Jeffrey A. Loeb ◽

Astrid Nehlig ◽

Asla Pitkänen ◽

...

Keyword(s):

Animal Models ◽

Epilepsy Therapy ◽

Therapy Development

Download Full-text

Challenges in modelling the Charcot-Marie-Tooth neuropathies for therapy development

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-318834 ◽

2018 ◽

Vol 90 (1) ◽

pp. 58-67 ◽

Cited By ~ 28

Author(s):

Manisha Juneja ◽

Joshua Burns ◽

Mario A Saporta ◽

Vincent Timmerman

Keyword(s):

Animal Models ◽

Genetic Heterogeneity ◽

Cellular Reprogramming ◽

Disease Modelling ◽

Gene Technology ◽

Technological Advancement ◽

Charcot Marie Tooth ◽

Precise Diagnosis ◽

Therapy Development ◽

Shed Light

Much has been achieved in terms of understanding the complex clinical and genetic heterogeneity of Charcot-Marie-Tooth neuropathy (CMT). Since the identification of mutations in the first CMT associated gene, PMP22, the technological advancement in molecular genetics and gene technology has allowed scientists to generate diverse animal models expressing monogenetic mutations that closely resemble the CMT phenotype. Additionally, one can now culture patient-derived neurons in a dish using cellular reprogramming and differentiation techniques. Nevertheless, despite the fact that finding a disease-causing mutation offers a precise diagnosis, there is no cure for CMT at present. This review will shed light on the exciting advancement in CMT disease modelling, the breakthroughs, pitfalls, current challenges for scientists and key considerations to move the field forward towards successful therapies.

Download Full-text

Duchenne Muscular Dystrophy Animal Models

10.5772/intechopen.96738 ◽

2021 ◽

Author(s):

Tatiana V. Egorova ◽

Ivan I. Galkin ◽

Yulia V. Ivanova ◽

Anna V. Polikarpova

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Animal Models ◽

Structural Protein ◽

Gene Deletions ◽

Advantages And Disadvantages ◽

Potential Applications ◽

Fundamental Research ◽

Therapy Development ◽

The Moment

Duchenne muscular dystrophy is a complex and severe orphan disease. It develops when the organism lacks the expression of dystrophin - a large structural protein. Dystrophin is transcribed from the largest gene in the human genome. At the moment, there is no cure available. Dozens of groups all over the world search for cure. Animal models are an important component of both the fundamental research and therapy development. Many animal models reproducing the features of disease were created and actively used since the late 80’s until present. The species diversity spans from invertebrates to primates and the genetic diversity of these models spans from single mutations to full gene deletions. The models are often non-interchangeable; while one model may be used for particular drug design it may be useless for another. Here we describe existing models, discuss their advantages and disadvantages and potential applications for research and therapy development.

Download Full-text

Reductionist thinking and animal models in neuropsychiatric research

Behavioral and Brain Sciences ◽

10.1017/s0140525x18001231 ◽

2019 ◽

Vol 42 ◽

Cited By ~ 1

Author(s):

Nicole M. Baran

Keyword(s):

Animal Models ◽

Mental Disorders ◽

Environmental Factors ◽

Neuropsychiatric Disorders ◽

Model Organisms ◽

Developmental Genetic ◽

Term Study ◽

Genetic And Environmental Factors ◽

Mechanisms Of Plasticity

AbstractReductionist thinking in neuroscience is manifest in the widespread use of animal models of neuropsychiatric disorders. Broader investigations of diverse behaviors in non-model organisms and longer-term study of the mechanisms of plasticity will yield fundamental insights into the neurobiological, developmental, genetic, and environmental factors contributing to the “massively multifactorial system networks” which go awry in mental disorders.

Download Full-text

Inflammational Animal Models for Schizophrenia

Zeitschrift für Psychologie ◽

10.1027/2151-2604/a000216 ◽

2015 ◽

Vol 223 (3) ◽

pp. 157-164 ◽

Cited By ~ 1

Author(s):

Georg Juckel

Keyword(s):

Animal Model ◽

Animal Models ◽

Immune Activation ◽

Microglial Activation ◽

Treatment Options ◽

Early Adulthood ◽

Brain Regions ◽

Synaptic Connections ◽

Preventive Interventions ◽

Immunological System

Abstract. Inflammational-immunological processes within the pathophysiology of schizophrenia seem to play an important role. Early signals of neurobiological changes in the embryonal phase of brain in later patients with schizophrenia might lead to activation of the immunological system, for example, of cytokines and microglial cells. Microglia then induces – via the neurotoxic activities of these cells as an overreaction – a rarification of synaptic connections in frontal and temporal brain regions, that is, reduction of the neuropil. Promising inflammational animal models for schizophrenia with high validity can be used today to mimic behavioral as well as neurobiological findings in patients, for example, the well-known neurochemical alterations of dopaminergic, glutamatergic, serotonergic, and other neurotransmitter systems. Also the microglial activation can be modeled well within one of this models, that is, the inflammational PolyI:C animal model of schizophrenia, showing a time peak in late adolescence/early adulthood. The exact mechanism, by which activated microglia cells then triggers further neurodegeneration, must now be investigated in broader detail. Thus, these animal models can be used to understand the pathophysiology of schizophrenia better especially concerning the interaction of immune activation, inflammation, and neurodegeneration. This could also lead to the development of anti-inflammational treatment options and of preventive interventions.

Download Full-text