Dr Richard Mead

Department of Neuroscience
Sheffield Institute of Translational Neuroscience
University of Sheffield
385a Glossop Road
Sheffield
S10 2HQ

Telephone: +44 (0)114 2222256
Email: r.j.mead@sheffield.ac.uk

Biography

I received my PhD in Neuroimmunology on ‘The role of complement in experimental models of multiple sclerosis (MS)’ from the University of Cardiff in 2001. I moved to Celltech (now part of UCB Pharma) first as a pharmacologist and then pharmacology team leader responsible for MS preclinical development. I joined the Neuroscience department in Sheffield in 2005 to establish in vitro and preclinical small molecule screening programmes for Motor Neuron Disease and in 2010 took up a Research Fellowship in Translational Neuroscience within the Sheffield Institute for Translational Neuroscience (SITraN) to continue this work.

Research Interests

My research interests are in discovery of novel therapies for MND. In particular we have identified a CNS penetrating Nrf2-ARE pathway activating molecule with activity in MND/ALS preclinical models. The Nrf2-ARE pathway is an endogenous system for protecting cells against oxidative stress and some small molecules can activate this pathway. In collaboration with Professor Shaw we have taken a compound from discovery through to orphan designation, with the European Medicines Agency, for treatment of MND/ALS.
I am also interested in developing improved methods for preclinical testing in MND (see publication 1)

Teaching Interests

I teach on the MSc courses in Translational Neuroscience and Molecular Medicine focussing on preclinical study design, analysis of motor function, statistics and drug development. I enjoy training and supervising MSc and BMedSci students on research projects. I also do some scientific outreach work in local schools as a speaker for Understanding Animal Research.

Current Interests

• Identification of novel, non-reactive small molecule activators of the Nrf2-ARE pathway. The Nrf2-ARE pathway is a key endogenous system for increasing cellular defences against oxidative stress. Small molecules that activate this pathway generally react with sulphydryl (SH) groups on Keap1, the cytoplasmic inhibitor of Nrf2. We have developed fluorescence polarisation assays to probe the interaction between Nrf2 and Keap1 with the goal of screening focussed libraries for their ability to disrupt this interaction as opposed to reacting with SH groups on Keap1.

• Screening for modifiers of TDP43 localisation. We have access to MND patient fibroblasts which show mis-localisation of TDP43 and are developing high-content, image based screens which can measure this mis-localisation, with the ultimate goal of screening for compounds that can correct this defect.

• Anti-Inflammatory therapy in ALS. Given the well described role of non-neuronal cells such as astrocytes and microglia in driving disease progression and inflammation in MND/ALS, we are testing a range of anti-inflammatory therapies in our pre-clinical ALS/MND model.

Key Publications

1. Mead RJ, Bennet E, , Kennerly A, Sharp P, Sunyach C, Kasher P, Berwick J, Pettmann B, Battaglia G, Azzouz M, Grierson A, Shaw PJ. Optimisation of pre-clinical pharmacology studies in the SOD1G93A transgenic mouse model of Motor Neuron Disease. 2010. PLoS One 2011. 6(8), e23244.
2. Barber SC, Higginbottom A, Mead RJ, Barber S and Shaw PJ. (2009) An in vitro screening cascade to identify neuroprotective antioxidants in ALS. Free Radical Biology and Medicine 2009. 46(8), 1127-38.
3. Mead RJ, Neal JW, Griffiths MR, Linington C, Botto M, Lasmmann H and Morgan BP. (2004). Deficiency of the complement regulator CD59a enhances disease severity, demyelination, and axonal injury in murine acute experimental allergic encephalomyelitis. Laboratory Investigation 84 (1), 21-28.
4. Mead RJ, Singaroah S, Neal, JW, Lasmmann H and Morgan BP. (2002) The membrane attack complex of complement causes severe demyelination in association with axonal injury. Journal of Immunology 168, 458-465.

Key Patents

1. Method for the treatment of Multiple Sclerosis by Inhibiting IL17 activity. Inventors Christie MI, Mead RJ, Robinson MK, Rapecki, SE. (2005) EP1687026 2006-08-09. WO2005051422. CA2544920. AU2004292393.
2. Therapeutics for neurological disorders. Inventors Shaw P, Mead R, Higginbottom A, Barber SC (2010). Publication number WO2010046710 (A1) describing NRF2 activating compounds for treatment of neurodegenerative diseases.