Honorary Consultant Neurologist, Newcastle upon Tyne Hospitals NHS Foundation Trust
A. Non-Motor Complications in Parkinson’s Disease
My primary short- and long-term aims are to improve our knowledge of the evolution of cognitive impairment in non-demented PD patients and also the pathophysiological basis for this devastating complication.
(i) Working within the overall IAH / DLB Framework and Strategy
The Dementia with Lewy Bodies (DLB) programme is now “bridging” the clinical spectrum more comprehensively between DLB and PDD. Professor Ian McKeith is the Clinical lead on the current MRC-funded DLB programme, and we foresee the shift towards PDD as being an integral component of future grant applications.
(ii) Developing large community-based Parkinson’s disease cohorts
A prospective study of prevalent people with Parkinson’s disease (PD) in Sunderland examined the relationship between falls, orthostatic hypotension and cognition in nearly 180 cases. We now plan to recruit an incident community-based PD cohort in Newcastle and Gateshead. This population will provide an unparalleled opportunity for un-biased, prospective risk factor clinical, imaging and genetic studies for dementia in PD. The study is a 5-year, PDS-funded collaboration with Cambridge and Imperial College, London.
(iii) Treatment of Dementia in Parkinson’s Disease
I lead applicant on a £3.4m proposal to the HTA to undertake a UK-based, multi-centre, double-blind, placebo-controlled trial of the cholinesterase inhibitor donepezil in early dementia associated with PD. The trial (MUSTARDD-PD) was conceived via DeNDRoN. We currently await news regarding the outcome of the preliminary application.
(iv) Depression in Parkinson’s Disease
I am principle investigator in a UK multicentre proposal (coordinating site, King’s College London, Chief Investigaotr Professor Richard Brown; £1.2m PDS funded) to better define depression in PD and its determinants, with a view to undertaking a therapeutic trial.
B. Progressive Supranuclear Palsy (PSP)
In an original study, funded by the PSP (Europe) Association, over 180 cases were identified and short term research aims included following up local patients as part of a natural history study, with pathological correlation. This work also included serial magnetic resonance spectroscopic and electro-oculographic studies, to assess the utility of these tests in early diagnosis and prognosis. Pathological studies are in collaboration with Professor Andrew Lees (London).
The PSP studies are now integrated more within the DLB / PDD programme. A project, cortical and striatal cholinergic receptor subtypes in PSP, Alzheimer’s disease and DLB (funded by the Society for PSP: Burn, Piggott MA and Lees, London UK) undertook preliminary neurochemical studies and ongoing work funded by the PSP (Europe) Association, is extending this work further.
I am lead applicant in the UK for a joint NINDS-PSP (Europe) Association funded study of the tolerability of lithium in PSP, with a view to larger randomised controlled trials to examine whether this agent has disease-modifying effects.
1. Co-applicant: Establishment of a Clinical Ageing Research Unit (CARU). Wellcome Trust: 2006 (£7.5 million) (G Ford, D Burn, JT O'Brien, R Taylor, IG McKeith, J Edwardson, T Kirkwood).
2. Co-applicant: The role of mitochondrial DNA in the pathogenesis of Parkinson’s disease. Parkinson’s Disease Society, UK: June 2007- May 2010 (£181207) (Chinnery PF, Burn DJ).
3. Co-applicant: Does cueing improve gait in people with Parkinson’s disease with dementia? Parkinson’s Disease Society, UK: August 2007 - July 2008 (£8184) (Rochester L, Burn DJ, Nieuwboer A).
4. Lead investigator: Visual symptoms in Parkinson’s disease and Parkinson’s disease dementia: Association with ocular and retinal pathology, visuo-perceptual deficits and impact on daily living and quality of life. Parkinson’s UK: November 2007-October 2010 (£206,446) (Archibald N, Mosimann UP, Clarke MP, Burn DJ).
5. Co-applicant: The role of common DNA variants in Parkinson’s disease. Wellcome Trust: February 2008 – January 2009 (£53,885) (Wood NW, Barker RA, Burn DJ, Chinnery PF, Hardy J, Morris HR, Morrison K, Clarke CE, Williams N).
6. Chief investigator: Predicting Dementia in Parkinson’s disease: A genotypic and phenotypic study (ICICLE-PD). Parkinson’s UK REF J0802, UK: October 2007 – September 2012 (£1,184,209) (Burn DJ, Barker RA, Brooks DJ, O’Brien JT, McKeith IG, Chinnery PF, Owen AM, Brayne CEG, Robbins T, Sawcer S, Coleman S).
7. Co-applicant: Genome-wide association studies in Parkinson’s disease. Parkinson’s UK REF J-0804: January 2009 – December 2010 (£292,590) (Wood NW, Hardy J, Barker RA, Burn DJ, Chinnery PF, Morris HR, Morrison K, Williams NM).
8. Chief investigator: Multicentre UK Study of the acetylcholinesterase inhibitor donepezil in early dementia associated with Parkinson's disease (MUSTARDD-PD). NIHR Health Technology Assessment Programme Project REF: 08/14/13: 1st Sept 2010 – 31st Aug 2015 (£2,119,113) (Burn DJ, Barker RA, Braithwaite B, Burns A, Clarke CE, Hindle JV, Knapp M, Lees AJ, Leroi I, McColl E, McKeith IG, O’Brien JT, Steen IN, Wheatley K).
9. Co-applicant: The Parkinson’s Repository of Biomarkers and Networked Datasets (PROBAND) programme: A UK national clinical consortium linking novel biomarker research to clinical expression, and progression rates, in Parkinson’s disease. Parkinson’s UK: 2011-2015 (£1,633,503) (Grosset D, Burn DJ, Barker RA, Ben-Shlomo Y, Bajaj N, Hardy J, Wood NW, Morris HR).
10. Principal applicant: Apomorphine: A modifier of amyloid deposition in Parkinson’s disease? Parkinson’s UK REF K-1101: October 2011 - April 2012 (£29,318) (Burn DJ, Revesz T, Lees AJ).
11. Principal applicant: Clinical trial to compare cognitive scales. Michael J Fox Foundation: 1st October 2011 - 30th September 2016 ($1,480,548) (Burn DJ, Weintraub D).
12. Principal applicant: A Biomedical Research Unit in Lewy Body Dementia. NIHR: 1st April 2012 - 31st March 2017 (£4.5M) (Burn DJ, McKeith IG, O’Brien JT, Kirkwood TBL, Chinnery PF, Ford GA).
13. Principal applicant: Predicting cognitive profiles in Parkinson’s disease: A multimodal approach. Michael J Fox Foundation: 1st November 2011 - 31st October 2013 ($153,342) (Burn DJ, Rochester L, O’Brien JT, Coleman SY, Baker MR).
14. Principle investigator in Parkinson's disease drug studies, including trials of cholinesterase inhibitors (rivastigmine and donepezil), memantine, ACP-103 (pimavanserin; UK Chief Investigator), droxidopa, rasagiline (ADAGIO UK Chief Investigator), rotigotine, istradefylline, intranasal apomorphine, entacapone, preladenant (UK Chief Investigator) and putative neuroprotective agents. Also UK Chief Investigator in NIH-funded tolerability of low dose lithium in PSP, davudenant as a neuroprotectant in PSP (Allon) studies.