Animal Models of Drug-Resistant Epilepsy as Tools for Deciphering the Cellular and Molecular Mechanisms of Pharmacoresistance and Discovering More Effective Treatments

Cells, Journal Year: 2023, Volume and Issue: 12(9), P. 1233 - 1233

Published: April 24, 2023

In the last 30 years, over 20 new anti-seizure medicines (ASMs) have been introduced into market for treatment of epilepsy using well-established preclinical seizure and models. Despite this success, approximately 20–30% patients with drug-resistant (DRE). The current approach to ASM discovery DRE relies largely on drug testing in various model systems that display varying degrees resistance. recent attempts made include more etiologically relevant models evaluation a investigational drug. Such played an important role advancing greater understanding at mechanistic level hypothesis as experimental evidence becomes available. This review provides critical discussion pharmacology adult focal allow selection responders nonresponders those pharmacoresistance per se two or ASMs. addition, animal major genetic epilepsies is discussed. Importantly, addition chemical compounds, several discussed here can be used evaluate other potential therapies such neurostimulation, dietary treatments, gene therapy, cell transplantation. also discusses challenges associated identifying novel absence mechanisms contribute DRE. Finally, lessons learned from profile recently approved highly efficacious broad-spectrum cenobamate.

Language: Английский

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The Impact of Artificial Intelligence on Optimizing Diagnosis and Treatment Plans for Rare Genetic Disorders

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 11, 2023

Rare genetic disorders (RDs), characterized by their low prevalence and diagnostic complexities, present significant challenges to healthcare systems. This article explores the transformative impact of artificial intelligence (AI) machine learning (ML) in addressing these challenges. It emphasizes need for accurate early diagnosis RDs, often hindered clinical heterogeneity. discusses how AI ML are reshaping healthcare, providing examples effectiveness disease diagnosis, prognosis, image analysis, drug repurposing. highlights AI's ability efficiently analyze extensive datasets expedite showcasing case studies like Face2Gene. Furthermore, tailors treatment plans leveraging deep (DL) create personalized therapeutic regimens. role discovery, including identification potential candidates rare treatments. Challenges limitations related ethical, legal, technical, human aspects, addressed. underscores importance data ethics, privacy, algorithmic fairness, as well standardized evaluation techniques transparency research. second-generation systems that prioritize patient-centric care, efficient patient recruitment trials, significance high-quality data. The integration with telemedicine, growth health databases, recommendations identified promising directions field. In summary, this provides a comprehensive exploration revolutionizing while considering ethical implications rapidly evolving landscape.

Language: Английский

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Complexity in Genetic Epilepsies: A Comprehensive Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14606 - 14606

Published: Sept. 27, 2023

Epilepsy is a highly prevalent neurological disorder, affecting between 5–8 per 1000 individuals and associated with lifetime risk of up to 3%. In addition high incidence, epilepsy heterogeneous variation including, but not limited the following: severity, age onset, type seizure, developmental delay, drug responsiveness, other comorbidities. Variable phenotypes are reflected in range etiologies including genetic, infectious, metabolic, immune, acquired/structural (resulting from, for example, severe head injury or stroke), idiopathic. This review will focus specifically on epilepsies genetic cause, testing, biomarkers epilepsy.

Language: Английский

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Sigma-1 receptor agonist PRE-084 confers protection against TAR DNA-binding protein-43 toxicity through NRF2 signalling

Redox Biology, Journal Year: 2022, Volume and Issue: 58, P. 102542 - 102542

Published: Nov. 17, 2022

Language: Английский

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Current status of research in rare genetic disorders and drug discovery in India

Journal of Biosciences, Journal Year: 2024, Volume and Issue: 49(1)

Published: Feb. 20, 2024

Current status of research in rare genetic disorders and drug discovery India 11The major health agenda so far has prioritized infectious diseases public health.Given the socioeconomic conditions poverty, a large fraction Indian population is exposed to infections from different pathogens, most notably enteric, parasitic, mycobacterial, viral.In recent years, however, there been decline spread these with better surveillance, availability therapy, improvement conditions, education.It now being realized that non-communicable are reaching epidemic proportions greater emphasis on diagnosis management diseases.The proportion deaths due gone up substantially was found be about 61.8% all 2016 (https://www.wbhealth.gov.in/NCD/)The four categories cardiovascular, chronic respiratory, diabetes, cancer, some which share common risk factors including behaviour related lifestyle.There shift Government policy give more importance preventing managing diseases.Programs definite budget allocation have launched by Ministry Health Family Welfare (MoHFW) (National Mission 2023) for control diseases.While initiatives laudable, they tend include only commonly known diseases.Relatively diseases, origin, not place programs.In witnessing gradual increase awareness disorders, coming attention scientists, clinicians, policymakers.It becoming clear as generally perceived, collective burden among substantial.Moreover, therapies available treatment than 95% diseases.Unfortunately, priced much above purchasing power Indians, partly because their development production done outside country, intellectual property new technology platforms, basis novel therapeutics, owned international pharmaceutical companies.Broadly, mutations 2900 genes attributed 7300 individually nature.Studying can improve our understanding relationship between gene function physiology.These natural variants powerful resource provide immense opportunities scientists understand basic biology through genotype-phenotype correlation.In meeting organized level (Rare Genetic Diseases Research Summit it became significant number clinicians working diseases.However, carried out scattered way across country.It important document form single volume useful reflection progress made, gap areas, plan future directions this country.This special issue showcase disease efforts India.It should also help increasing vast area high translation.

Language: Английский

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Stage‐by‐stage exploration of normal embryonic development in the Arabian killifish, Aphanius dispar

Developmental Dynamics, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

Arabian killifish, Aphanius dispar, lives in marine coastal areas of the Middle East, as well streams that experience a wide range salinities and temperatures. It has been used mosquito control agent for studying toxicities environmental pollutants. A. dispar's eggshell (chorion) embryos are highly transparent suitable high resolution microscopic observations, offering excellent visibility live tissues.

Language: Английский

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Targeting Ferroptosis in Rare Neurological Disorders Including Pediatric Conditions: Innovations and Therapeutic Challenges

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 265 - 265

Published: Jan. 22, 2025

Ferroptosis, characterized by iron dependency and lipid peroxidation, has emerged as a key mechanism underlying neurodegeneration in rare neurological disorders. These conditions, often marked significant therapeutic gaps high unmet medical needs, present unique challenges for intervention development. This review examines the involvement of ferroptosis disease pathogenesis, focusing on its role oxidative damage neuronal dysfunction. We explore recent pharmacological advancements, including chelators, peroxidation blockers, antioxidant-based strategies, designed to target ferroptosis. While these approaches show promise, such heterogeneity, limited diagnostic tools, small patient cohorts hinder progress. Furthermore, we discuss translational regulatory barriers implementing ferroptosis-based therapies clinical practice. By addressing obstacles fostering innovative solutions, this underscores potential ferroptosis-targeting strategies revolutionize treatment paradigms

Language: Английский

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Genetics of Physiological Variation Within and Between Larval Wild-Type AB and Backcrossed NHGRI-1 Zebrafish (Danio rerio)

Fishes, Journal Year: 2025, Volume and Issue: 10(2), P. 59 - 59

Published: Jan. 31, 2025

Changes in the environment promote variations fish physiological responses. Genetic variation also plays a role variation. To explore of genetics variation, we assessed cardiac function (heart rate, stroke volume, and output), oxygen consumption, yolk conversion efficiency, cost development embryonic larval AB wild-type NHGRI-1 zebrafish (low heterozygosity line backcrossed from wild-type) exposed to different temperature regimes. Fish were fertilization 7 days post-fertilization (dpf) control conditions (28 °C, 21% O2) or low (23 O2), high (33 moderate hypoxia 13% severe 10% O2). We hypothesized that (1) variables will respond similarly both lines (2) data variability be lower than zebrafish. Cardiac decreased at Oxygen consumption was increased by higher fish. Yolk efficiency Cost mainly hypoxia-treated Supporting our hypothesis contributes showed significantly coefficients 84% endpoints. conclude there is strong genetic component fishes are useful models for reducing ‘noise’ backgrounds research fish, which may aid interpretation experimental results facilitate reproducibility.

Language: Английский

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Toxicological screening of jambolan hydroalcoholic extract (Syzygium Cumini (L.) Skeels) in zebrafish (Danio rerio)

Toxicology Reports, Journal Year: 2025, Volume and Issue: unknown, P. 101999 - 101999

Published: March 1, 2025

Jambolan (Syzygium cumini (L.) Skeels) is an important source of phenolic compounds, especially anthocyanins, known for their biological properties. This study investigated the acute toxicity jambolan hydroalcoholic extract (JE) in zebrafish (Danio rerio) at different life stages. JE, obtained from freeze-dried fruits, was analyzed by high-performance liquid chromatography (HPLC) and found to be rich total compounds (TPC). A 15 were identified HPLC extracts, mainly anthocyanins (≈ 82 % TPC), JE presented relevant antioxidant properties vitro tests. Exposure concentrations between 50 200 µg/ml resulted increased malformations mortality both embryos adult zebrafish, doses 300 400 lethal animals. Lethal (LC50) estimated 118.4 68.86 adults. Despite no significant cardiovascular or neurological toxicities, behavioral impacts observed lower (10 µg/ml), indicating a nonmonotonic concentration-response curve. Our findings suggest that moderate (around 25 µg/ml) are safe zebrafish; however, further studies needed ensure its safety efficacy under health conditions exposure regimes.

Language: Английский

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Using Single-Cell RNA sequencing with Drosophila, Zebrafish, and mouse models for studying Alzheimer’s and Parkinson’s disease

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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