The impact of genetics on future drug discovery in schizophrenia
| Autor: | Hiroshi Yamada, Yuji Kondo, Katsunori Tajinda, Gerard J. Marek, Noah M. Walton, Mitsuyuki Matsumoto |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetics Drug discovery Schizophrenia (object-oriented programming) Drugs Investigational Disease Biology Bioinformatics Precision medicine Polymorphism Single Nucleotide Biomarker (cell) 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Drug Design Drug Discovery Schizophrenia Animals Humans SNP Genetic Predisposition to Disease 030217 neurology & neurosurgery Exome sequencing Genome-Wide Association Study Genetic association |
| Zdroj: | Expert Opinion on Drug Discovery. 12:673-686 |
| ISSN: | 1746-045X 1746-0441 |
| DOI: | 10.1080/17460441.2017.1324419 |
| Popis: | Failures of investigational new drugs (INDs) for schizophrenia have left huge unmet medical needs for patients. Given the recent lackluster results, it is imperative that new drug discovery approaches (and resultant drug candidates) target pathophysiological alterations that are shared in specific, stratified patient populations that are selected based on pre-identified biological signatures. One path to implementing this paradigm is achievable by leveraging recent advances in genetic information and technologies. Genome-wide exome sequencing and meta-analysis of single nucleotide polymorphism (SNP)-based association studies have already revealed rare deleterious variants and SNPs in patient populations. Areas covered: Herein, the authors review the impact that genetics have on the future of schizophrenia drug discovery. The high polygenicity of schizophrenia strongly indicates that this disease is biologically heterogeneous so the identification of unique subgroups (by patient stratification) is becoming increasingly necessary for future investigational new drugs. Expert opinion: The authors propose a pathophysiology-based stratification of genetically-defined subgroups that share deficits in particular biological pathways. Existing tools, including lower-cost genomic sequencing and advanced gene-editing technology render this strategy ever more feasible. Genetically complex psychiatric disorders such as schizophrenia may also benefit from synergistic research with simpler monogenic disorders that share perturbations in similar biological pathways. |
| Databáze: | OpenAIRE |
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