Professor Malcolm MacLeod (BSc(Hons) MBChB PhD FRCP Ed)
Professor of Neurology and Translational Neuroscience
Responsibilities & affiliations
- Member, UK Home Office Animals in Science Committee
- Commissioner, Commission for Human Medicines, Medicines and Healthcare Products Regulatory Agency (MHRA)
Every week around 3500 new pieces of research involving animals are published. It is almost impossible for anyone to stay up to date with current knowledge. We have also shown that much of that work is at substantial risk of bias - and the effects observed in animals may be substantially overstated as a consequence.
In our research we are developing tools to provide unbiased summaries of what is already known, including tools to assess whether effects in animals may be overstated. We then use this information to help guide better design of clinical trials testing treatments in humans.
Examples of trials we have helped design using this approach include EuroHYP-1 - a trial of brain cooling in stroke - and MS-SMART, a trial in secondary progressive multiple sclerosis.
Research aims and areas of interest
My group has led the development and application of systematic review and meta-analysis to the analysis of data from animal studies modelling neurological diseases such as stroke. This work allows an overview of how effective the drug is in animals; identification of the limits to efficacy in animals which might be relevant to human clinical trials; and an assessment of the risk that the findings of animal studies are biased because of poor experimental design.
Now we are using this information to provide guidance to those using, funding, publishing and measuring the contribution of research involving animals. With others we are seeking to develop ways of providing real-time summaries of the current state of knowledge to guide future research and to help with research resource allocation decisions. We are also developing techniques of meta-moderation and mediation analysis to better understand pathophysiological pathways in animal models of human diseases such as multiple sclerosis.
I am involved in clinical trials in stroke including EuroHYP-1, a 1500-patient trial of brain cooling for acute ischaemic stroke; FOCUS, a trial of antidepressants following stroke; and phase 1 studies testing the effectiveness of local brain cooling in reducing brain temperature.
Research group members
- Dr Emily Sena, Senior Post Doc and Deputy Group Leader
- Dr Gillian Currie, Post-doc
- Dr Jing Liao, Programmer
- Zsanett Bahor, PhD student
- Alexandra Bannach-Brown, Joint Aarhus-Edinburgh MSc/PhD student
- Prof David Howells, Florey Neurosciences Institute, Melbourne, Australia
- Prof Andrew Rice, Imperial College, London
- Prof Uli Dirnagl, Charite, Berlin
- Prof Greg Wegener, Aarhus University, Denmark
Sources of funding
- European Commission Seventh Framework Programme (FP7)
- NC3Rs (National Centre for the Replacement, Refinement & Reduction of Animals in Research)
The reproducibility opportunity
Nature Human Behaviour
Contribution to journal › Comment/debate (Published)
'Small vessels, dementia and chronic diseases -molecular mechanisms and pathophysiology' Workshop proceedings
Clinical Science, vol. 132, no. 8, pp. 851-868
Contribution to journal › Review article (E-pub ahead of print)
Effect size and statistical power in the rodent fear conditioning literature - A systematic review
PLoS One, vol. 13, no. 4, pp. e0196258
Contribution to journal › Review article (Published)
NXY-059, a Failed Stroke Neuroprotectant, Offers No Protection to Stem Cell-Derived Human Neurons
Journal of Stroke and Cerebrovascular Diseases
Contribution to journal › Article (E-pub ahead of print)
A systematic review and meta-analysis of topoisomerase inhibition in pre-clinical glioma models
Oncotarget, vol. 9, no. 13, pp. 11387-11401
Contribution to journal › Article (Published)