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Personal profile

Research interests

Alan leads a programme of research in Parkinson’s disease and other movement disorders at the Bristol Brain Centre, Southmead Hospital. Since 2010 Alan has been Principal Applicant or Co-applicant on £5-million of peer reviewed grant funding (Parkinson’s UK, NIHR) and £1 million of industry or local charities research funding.

The research programme in Parkinson’s has two arms:
• Addressing unmet symptom needs, “helping people with Parkinson’s live better today” and;
• Addressing unmet disease modification needs, “giving people with Parkinson’s hope for the future”.
Studies to address unmet symptom needs include observational or clinical trial investigations of medicinal products or devices. Experiments to address unmet disease-modification needs are clinical trial and laboratory based (for further details see Research tab).

Investigations into Unmet Symptom Needs:

We wish to case impact the common, disabling and costly symptoms created by Parkinson’s axial manifestations (falls, postural instability, gait-freezing) and neuropsychiatric and or cognitive complications.

• Led by Emily Henderson and in collaboration with Professor Yoav Ben Shlomo, Alan and colleagues completed a successful investigator-led single-centre phase II clinical trial to assess if the cholinesterase inhibitor Rivastigmine could be repositioned, through its effect on increased attention, to reduce gait instability and falls in people with Parkinson’s without dementia. The primary endpoint, improvement in step time variability, and a secondary endpoint, a reduction in falls (40%), was reached. Alan was joint last author on the subsequent paper in Lancet Neurology, 2016. The study was funded as a Research Training Fellowship by Parkinson’s UK for Emily Henderson. An HTA has been awarded in 2017 by the NIHR for a confirmatory phase III multi-centre study where falls are the primary outcome and as part of which there will be an economic cost benefit analysis.
• Alan collaborates in studies led by Drs Coulthard and Grogan to understand cognitive changes in Parkinson’s and the role of dopamine in the formation of memory.
• NBT is one of the largest providers of Deep Brain Stimulation Surgery for Movement Disorders in the UK. Alan is Neurology lead for this service and integrated with this service is a programme of DBS research that involves both novel stimulation devices and novel targets for stimulation.
• With Professors Apps and Gilchrist, University of Bristol and Dr Boca, Dr Rolinski and Hannah Findlay, Alan is preparing an MRC Programme Grant to determine the effects of reward and training on motor adaptation, in Parkinson’s and prodromal Parkinson’s (REM Sleep Behaviour Disorder).
• In Bristol we have a unique digital health experimental facility known as SPHERE (Sensor Platform for Healthcare in a Residential Environment), which is a highly-instrumental living-lab (http://theinstitute.ieee.org/technology-topics/smart-technology/the-sphere-house-can-monitor-its-residents-health). Working with Professor Craddock, Director of SPHERE, Alan and Drs Morgan, Rolinski, Boca and Hannah Findlay are developing research to provide better outcome measures for trials of putative disease modifying agents in Parkinson’s.
• Since 2010 Alan has been Principal Investigator on 8 further multi-centre investigator-led or commercial studies in Parkinson’s and currently we have 5 investigator or commercial trials in set-up.

Investigations into Unmet Neuroprotection/Neurorestorative Needs:

Currently there are no treatments to slow the progression of Parkinson’s and over 70% of patients eventually develop dementia and a high-burden of social care.

• Alan was Chief Investigator of a single-centre, investigator-led, randomised placebo-controlled – followed by open-label clinical trial, to assess the safety and efficacy of intermittent bilateral intraputamenal Glial Cell Line-Derived Neurotrophic Factor (GDNF) infusions administered via convection-enhanced delivery (CED) on a monthly basis via a skull-mounted port in Parkinson’s. 41 subjects were randomised and over 1000 brain infusions administered between 2012 and 2017. The double-blind phase completed April 2016 and the open label extension phase completed February 2017. In addition to assessing the putative neurorestorative effect of GDNF, these investigations were the first to demonstrate the tolerability and feasibility of an intermittent infusion methodology for bypassing the blood brain barrier and to show successful convection-enhanced delivery in Parkinson’s. Alan led the complex collaboration between the stakeholders that included: a Canadian biotech industry (MedGenesis), a high-tech industry (Renishaw), North Bristol NHS Trust, Cardiff University and the University of British Columbia and two charities - Parkinson’s UK and the Cure Parkinson’s Trust. Subsequently Alan has been collaborating with MedGenesis and Pfizer to take this forward to a phase III confirmatory multi-centre trial. For a talk on this trial delivered at the Royal Institution, London, at primary study start in 2013 – see https://www.youtube.com/watch?v=h3ZDxnwwbzc. For an update talk on this trial delivered at the Royal College of Surgeons, London, in late 2016, see:https://www.youtube.com/watch?v=XcZQEct4yCI
• Alan is currently collaborating with investigators at the Universities of Lund and Helsinki and the Karolinska Institute for a separate investigation of an alternative growth factor, CDNF, in Parkinson’s.
• Alan has previously collaborated with researchers in Bristol and the U.S. to investigate molecular changes in Parkinson’s at the cell culture level utilising skin collected from patients with genetic forms of Parkinson’s to look at both fibroblasts (published in Nature Medicine) and induced pluripotent stem cells. Similarly, Alan has previously investigated the potential neuroprotective effect of human bone marrow stem cells on cultured dopaminergic neurons through trophic factor release.

In the past 5 years Alan has given multiple invited research lectures including at The Royal Institution, London, The Royal College of Physicians, London, The Royal College of Surgeons, London, The Royal College of Physicians, Edinburgh, The National Hospital for Neurology, Queen Square, London, Cambridge University, and outside the UK at international meetings in Dublin, the U.S. and Japan.


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