Drug discovery in ophthalmology: past success, present challenges, and future opportunities

BMC Ophthalmology
Nicholas J D GowerAlastair K Denniston

Abstract

Drug discovery has undergone major transformations in the last century, progressing from the recognition and refinement of natural products with therapeutic benefit, to the systematic screening of molecular libraries on whole organisms or cell lines and more recently to a more target-based approach driven by greater knowledge of the physiological and pathological pathways involved. Despite this evolution increasing challenges within the drug discovery industry are causing escalating rates of failure of development pipelines. We review the challenges facing the drug discovery industry, and discuss what attempts are being made to increase the productivity of drug development, including a refocusing on the study of the basic biology of the disease, and an embracing of the concept of 'translational research'. We consider what ophthalmic drug discovery can learn from the sector in general and discuss strategies to overcome the present limitations. This includes advances in the understanding of the pathogenesis of disease; improvements in animal models of human disease; improvements in ophthalmic drug delivery and attempts at patient stratification within clinical trials. As we look to the future, we argue that investment in ophthalm...Continue Reading

References

Nov 7, 1995·Proceedings of the National Academy of Sciences of the United States of America·L P AielloL E Smith
Mar 15, 1994·Biochemical and Biophysical Research Communications·S CostagliolaM Ludgate
Aug 10, 2000·Neoplasia : an International Journal for Oncology Research·D RibattiF Dammacco
Oct 7, 2003·Oncogene·Peter Anthony Campochiaro, Sean Francis Hackett
Dec 13, 2003·Endocrine Reviews·Bellur S PrabhakarTerry J Smith
Apr 27, 2004·Experimental Eye Research·M HalhalF Behar-Cohen
May 12, 2004·Nature Reviews. Drug Discovery·Napoleone FerraraWilliam Novotny
May 12, 2004·Nature Reviews. Drug Discovery·Bruce Booth, Rodney Zemmel
Oct 8, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·S John CurnowMike Salmon
Dec 31, 2004·The New England Journal of Medicine·Evangelos S GragoudasUNKNOWN VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group
Feb 3, 2005·Nature Reviews. Drug Discovery·Fredric J Cohen
Oct 6, 2006·The New England Journal of Medicine·Philip J RosenfeldUNKNOWN MARINA Study Group
Nov 14, 2006·Advanced Drug Delivery Reviews·Arto Urtti
Feb 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Raymond S DouglasTerry J Smith
Jun 14, 2008·The New England Journal of Medicine·Rama D JagerJoan W Miller
Sep 16, 2008·Thyroid : Official Journal of the American Thyroid Association·Terry J SmithAndrew G Gianoukakis
Oct 4, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Raymond S DouglasTerry J Smith
Nov 15, 2008·Nature Reviews. Drug Discovery·Ian Walker, Herbie Newell
Jul 9, 2009·Retina·Gholam A PeymanDarius M Moshfeghi
Jan 13, 2010·MAbs·Adith Venkiteshwaran
Feb 16, 2010·Pharmaceutical Research·Esther Eljarrat-BinstockAbraham J Domb
Feb 20, 2010·Nature Reviews. Drug Discovery·Steven M PaulAaron L Schacht
May 4, 2010·The AAPS Journal·Ripal GaudanaAshim K Mitra
Oct 6, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Patrick J RobertsMark A Socinski
Dec 25, 2010·Veterinary Ophthalmology·Alan L Weiner, Brian C Gilger
Mar 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kang ZhangGeorge A Williams
May 3, 2011·Nature Reviews. Drug Discovery·John Arrowsmith
Jun 2, 2011·Nature Reviews. Drug Discovery·Fabio PammolliMassimo Riccaboni
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Jun 28, 2011·Nature Reviews. Drug Discovery·David C Swinney, Jason Anthony
Jun 28, 2011·Drug Discovery Today·Youssef L Bennani
Oct 6, 2011·Ocular Immunology and Inflammation·Aurore MuselierAlain Bron

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Citations

Dec 15, 2016·Expert Opinion on Drug Delivery·Vibhuti AgrahariAshim K Mitra
Mar 23, 2017·Journal of Pharmaceutical Sciences·Upendra A ArgikarBindi Sohal
Oct 17, 2017·Advanced Healthcare Materials·Michelle L RataySteven R Little
Jul 20, 2018·Investigative Ophthalmology & Visual Science·Yulia KaluzhnyMitchell Klausner
Feb 23, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Michael J ReidTerry Podoll
Jan 6, 2017·Oxidative Medicine and Cellular Longevity·Yuhei Nishimura, Hideaki Hara
Jul 1, 2020·Ophthalmic Epidemiology·David Gu, Timothy M Janetos
Mar 12, 2021·Database : the Journal of Biological Databases and Curation·Shaikh Farhad HossainMd Altaf-Ul-Amin
Sep 28, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Kritika Nayak, Manju Misra
Jun 22, 2021·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Wei HuangBasil Rigas

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Methods Mentioned

BETA
surgical resection
xenograft

Clinical Trials Mentioned

NCT01749930
NCT01895972
NCT01749904
NCT02565173
NCT02246764
NCT02207621
NCT02207491
NCT02558374
NCT02558400
NCT02250612

Software Mentioned

MARINA
EyeGate

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