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Systematic Approach for Drug Repositioning of Anti-Epileptic Drugs.

ABSTRACT: Epilepsy is a central neurological disorder affecting individuals of all ages and causing unpredictable seizures. In spite of the improved efficacy of new antiepileptic drugs and novel therapy, there are still approximately 20%~30% of patients, who have either intractable or uncontrolled seizures. The epilepsy drug-target network (EDT) is constructed and successfully demonstrates the characteristics and efficacy of popularly used AEDs through the identification of causative genes for 60 epilepsy patients. We discovered that the causative genes of most intractable patients were not the targets of existing AEDs, as well as being very far from the etiological mechanisms of existing AEDs in the functional networks. We show that the existence of new drugs that target the causative genes of intractable epilepsy patients, which will be potential candidates for refractory epilepsy patients. Our systematic approach demonstrates a new possibility for drug repositioning through the combination of the drug-target and functional networks.

SUBMITTER: Ko Y

PROVIDER: S-EPMC6963462 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Systematic Approach for Drug Repositioning of Anti-Epileptic Drugs.

Ko Younhee Y Lee Chulho C Lee Youngmok Y Lee Jin-Sung JS

Diagnostics (Basel, Switzerland) 20191130 4

Epilepsy is a central neurological disorder affecting individuals of all ages and causing unpredictable seizures. In spite of the improved efficacy of new antiepileptic drugs and novel therapy, there are still approximately 20%~30% of patients, who have either intractable or uncontrolled seizures. The epilepsy drug-target network (EDT) is constructed and successfully demonstrates the characteristics and efficacy of popularly used AEDs through the identification of causative genes for 60 epilepsy ...[more]

PMID: 31801232

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Project description:Increase in global population and growing disease burden due to the emergence of infectious diseases (Zika virus), multidrug-resistant pathogens, drug-resistant cancers (cisplatin-resistant ovarian cancer) and chronic diseases (arterial hypertension) necessitate effective therapies to improve health outcomes. However, the rapid increase in drug development cost demands innovative and sustainable drug discovery approaches. Drug repositioning, the discovery of new or improved therapies by reevaluation of approved or investigational compounds, solves a significant gap in the public health setting and improves the productivity of drug development. As the number of drug repurposing investigations increases, a new opportunity has emerged to understand factors driving drug repositioning through systematic analyses of drugs, drug targets and associated disease indications. However, such analyses have so far been hampered by the lack of a centralized knowledgebase, benchmarking data sets and reporting standards. To address these knowledge and clinical needs, here, we present RepurposeDB, a collection of repurposed drugs, drug targets and diseases, which was assembled, indexed and annotated from public data. RepurposeDB combines information on 253 drugs [small molecules (74.30%) and protein drugs (25.29%)] and 1125 diseases. Using RepurposeDB data, we identified pharmacological (chemical descriptors, physicochemical features and absorption, distribution, metabolism, excretion and toxicity properties), biological (protein domains, functional process, molecular mechanisms and pathway cross talks) and epidemiological (shared genetic architectures, disease comorbidities and clinical phenotype similarities) factors mediating drug repositioning. Collectively, RepurposeDB is developed as the reference database for drug repositioning investigations. The pharmacological, biological and epidemiological principles of drug repositioning identified from the meta-analyses could augment therapeutic development.

Dataset Information

Systematic Approach for Drug Repositioning of Anti-Epileptic Drugs.

Publications

Systematic Approach for Drug Repositioning of Anti-Epileptic Drugs.

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