The impact of genetics on future drug discovery in schizophrenia

Expert Opinion on Drug Discovery
Mitsuyuki MatsumotoKatsunori Tajinda

Abstract

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. Ex...Continue Reading

References

Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M Gossen, H Bujard
Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·P C OrbanJ D Marth
Sep 1, 1992·Archives of General Psychiatry·J W NewcomerJ G Csernansky
Jan 1, 1991·Developmental Neuroscience·N BaumannJ C Turpin
Nov 5, 1999·Human Molecular Genetics·W L KimberA Wynshaw-Boris
Jul 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·David J GerberSusumu Tonegawa
Aug 29, 2003·The American Journal of Psychiatry·Anne S BassettRosanna Weksberg
Mar 17, 2004·Biological Psychiatry·Mark H CorriganUNKNOWN Sonepiprazole Study Group
Jun 1, 2004·The American Journal of Psychiatry·Herbert Y MeltzerUNKNOWN Meta-Trial Study Group
Sep 29, 2004·Biochemical Pharmacology·Elisabeth RüttimannBernhard Bettler
Jul 12, 2005·American Journal of Medical Genetics. Part a·Marie-France PortnoïSandrine Marlin
Sep 2, 2005·The Annals of Otology, Rhinology, and Laryngology·Chris HalpinHeidi L Rehm
May 11, 2006·Proceedings of the National Academy of Sciences of the United States of America·Richard PaylorElizabeth Lindsay
Sep 26, 2006·Biological Psychiatry·Barbara K LipskaJoel E Kleinman
Sep 28, 2006·Brain : a Journal of Neurology·Mathieu SévinFrédéric Sedel
Mar 21, 2007·Journal of Medical Genetics·Charles E SchwartzRoger E Stevenson
Jul 31, 2007·Biochemical and Biophysical Research Communications·Akio NakashimaKazuyoshi Yonezawa
Sep 26, 2007·Neurology·A Salin-CantegrelG A Rouleau
Jan 9, 2008·Archives of General Psychiatry·Tyrone D CannonRobert Heinssen
May 28, 2008·Nature Reviews. Genetics·Cliff Tabin
Jun 19, 2008·Nature Reviews. Genetics·Margit BurmeisterSebastian Zöllner
Jul 3, 2008·The American Journal of Psychiatry·Anantha ShekharChristian C Felder
Aug 1, 2008·Nature·Hreinn StefanssonKari Stefansson
Nov 13, 2008·Human Molecular Genetics·Susan E SwanbergJanine M LaSalle
Apr 21, 2010·Cell·Jon McClellan, Mary-Claire King
May 21, 2010·Nature Reviews. Neuroscience·Maria KarayiorgouJoseph A Gogos
Apr 15, 2011·Nature·Kristen J BrennandFred H Gage
Jul 12, 2011·Expert Opinion on Investigational Drugs·Bjørn H EbdrupBirte Glenthøj
Oct 25, 2011·Annual Review of Pathology·Michael R SantoroStephen T Warren
Nov 19, 2011·Nature Reviews. Neuroscience·Nicholas J Brandon, Akira Sawa
Dec 23, 2011·Annals of Human Genetics·Emmanuel Peprah
Mar 6, 2012·Progress in Retinal and Eye Research·Andreas Ohlmann, Ernst R Tamm
Apr 26, 2012·Schizophrenia Bulletin·Carol A TammingaSubroto Ghose
Jun 30, 2012·Science·Martin JinekEmmanuelle Charpentier

❮ Previous
Next ❯

Citations

Sep 25, 2017·International Journal of Molecular Sciences·Haitao WangWenhua Zheng
Oct 27, 2017·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Giulio PilusoUNKNOWN Italian Network for Research on Psychoses
Jun 23, 2018·Frontiers in Public Health·Pronab GangulyAhmed A Moustafa
Jun 27, 2020·Frontiers in Psychiatry·Sokichi HondaTakuma Mihara
Aug 15, 2020·Frontiers in Psychiatry·Saurav SeshadriKatsunori Tajinda
Jan 21, 2021·Expert Opinion on Drug Discovery·Marinos G SotiropoulosNikolaos Kokras

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antipsychotic Drugs

Antipsychotic drugs are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. Discover the latest research on antipsychotic drugs here

Related Papers

Expert Opinion on Drug Discovery
Graeme Benstead-HumeFrances M G Pearl
Genome Medicine
Candace T Myers, Heather C Mefford
Circulation Research
Sandosh PadmanabhanAnna F Dominiczak
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova
V E Golimbet
© 2022 Meta ULC. All rights reserved