UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Drug repurposing in neurological diseases: an integrated approach to reduce trial and error

Clout, AE; Della Pasqua, O; Hanna, MG; Orlu, M; Pitceathly, RDS; (2019) Drug repurposing in neurological diseases: an integrated approach to reduce trial and error. Journal of Neurology, Neurosurgery and Psychiatry , 90 (11) pp. 1270-1275. 10.1136/jnnp-2019-320879. Green open access

[img]
Preview
Text
Della Pasqua_Drug repurposing in neurological diseases. An integrated approach to reduce trial and error_AAM2.pdf - Accepted version

Download (482kB) | Preview

Abstract

Identifying effective disease modifying therapies for neurological diseases remains an important challenge in drug discovery and development. Drug repurposing attempts to determine new indications for pre-existing compounds and represents a major opportunity to address this clinically unmet need. It is potentially more cost effective and time efficient than de novo drug development and has yielded notable successes in neurological disorders. However, across all medical disciplines only 30% of repurposed drugs, and 10% of novel candidate molecules, gain market approval. One potentially significant contributor towards this limited success rate is an incomplete knowledge of the exposure-response relationships for the compounds of interest, and how these relate to the new indication, prior to commencing a new trial. We will provide an overview of the current approach to early stage drug repurposing and consider the issues contributing to inconclusive, or possibly falsely negative, Phase II and III trial outcomes in neurological diseases by including examples that illustrate the limitations of empirical evidence generation without a strong scientific basis for the dose rationale. We conclude with a framework suggesting a translational, iterative approach that integrates pharmacological, pharmaceutical and clinical expertise towards preclinical and early clinical drug development. This ensures appropriate dosing regimen, route of administration, and/or formulation are selected for the new indication before their evaluation in prospective clinical trials.

Type: Article
Title: Drug repurposing in neurological diseases: an integrated approach to reduce trial and error
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/jnnp-2019-320879
Publisher version: https://jnnp.bmj.com/content/90/11/1270.info
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10073344
Downloads since deposit
54Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item