Yorkshire Brain Research Centre – Strategy for 2015-2018
We have reviewed the initial fundraising strategy for the Yorkshire Brain Research
Centre in light of recent positive developments in the allocation of resources and
personnel in this area.
We are pleased to advise that in January 2015 the Neurosciences Clinical Services
Unit appointed a Clinical Trials Manager (Band 8a) for Neurosciences. The
appointment of a senior research nurse to manage the research nurse team was one
of the key aims of the appeal. In addition we have appointed a full-time Band 3
Clinical Trials Assistant with funding from the Clinical Research Network. This role
provides the administrative support for the neurology research team for which
funding was requested in the original strategy. The combination of these two posts
meets £380,000 of the total costs in the original bid.
We have also approached the CRN in Yorkshire and Humber for delivery time
funding for the specialist consultants in epilepsy and multiple sclerosis (0.1
wte/consultant). Both teams have made significant progress in recruiting patients to
clinical trials in Leeds. We will also explore the possibilities of further protected
research time at job plan reviews. 0.2 PA time for five years will meet £100,000 of
the original bid.
Finally, we also received a £60,000 donation for equipment in the Neurosciences
unit and have a commitment for further fundraising for equipment.
These additional resources for the neurology research team make possible the
submission of a revised funding proposal as follows;
We propose funding the Clinical Neurosciences Group for 0.1 wte/consultant to
provide supervision for the Clinical Research Fellowships:
0.1 wte protected research time for a consultant with an interest in
neurodegenerative disease (Dr Jane Alty)
0.1 wte protected research time for a consultant with an interest in epilepsy (Dr
Melissa Maguire)
0.1 wte protected research time for a consultant with an interest in multiple sclerosis
(Dr Helen Ford)

The approximate cost for 0.3 wte for 3 years would be £90,000.
The Clinical research fellowships aim to support young clinicians in training in the
conduct of research at the highest standard. We would like to establish the Robert
Ogden Brain Research fellowships in the areas of neurodegenerative disease,
epilepsy and multiple sclerosis. We would encourage the appointed fellows to apply
for external funding during the first year of their fellowships. The costs for funding
each fellow for 3 years would be £120,000.

The approximate cost for 3 research fellows for 3 years would be £360,000
In summary, we have gained substantive funding of £380,000 for two posts that were
part of the original strategy, and have bid successfully for consultant funded time, a
further £100,000 of the strategy. In addition, fund raising with the support and
involvement of LTHT patients has already proved successful, confirming that this
project is a strong basis for local fund raising.
These new resources have made it possible to propose initiating the YBRC project
with a reduced budget, refocussing fundraising on the new Brain Research
fellowships, with an aim of raising a total of £450,000 over 3 years; £150,000 per
year from 2015-2018. This more modest budget is an attainable goal within the time
frame, and should help to address any concerns that may exist about the
requirement to raise a large target sum in order to get this project underway.
Helen Ford
Consultant Neurologist
19th January 2015
Chris Inglehearn
Professor of Molecular Ophthalmology
Examples of potential projects
A longitudinal study to discover new biomarkers for neurodegenerative
disorders
Dr Jane Alty, Consultant Neurologist, LTHT
Mr Martin McKibbin, Consultant Ophthalmologist, LTHT
Dr Ewan Morrison, Senior Lecturer, Cell Biology research group, University of Leeds
Prof Chris Inglehearn, Professor of Molecular Ophthalmology, University of Leeds
This study aims to discover new biomarkers for an array of neurodegenerative
disorders such as Parkinson’s disease (PD), Progressive Supranuclear Palsy (PSP),
Multiple System Atrophy (MSA), Dementia with Lewy Bodies (DLB) and Corticobasal
Syndrome (CBS). There are currently no objective tests to distinguish these
conditions in clinic and physicians rely on subjective clinical assessment and
watchful waiting. This greatly impedes drug trials as many patients are only
diagnosed in the advanced phases of disease. New biomarkers are desperately
needed in order to improve diagnostic accuracy, precisely evaluate the response to
new treatments, and to investigate pathophysiology.
Two potentially novel biomarkers will be tested in this study. Defects in the process
by which cells dispose of malfunctioning mitochondria – “mitophagy” – are
increasingly being recognised as a significant contributor to these disorders. Work in
Leeds has led to the development of a simple and robust cell-based assay of
mitophagy (Morrison et al 2011, J. Neurochem. 116, 342-349). With modification,
this assay has the potential to be used to detect defective mitophagy in cells present
in patient blood samples. In addition, patients will be subject to optical coherence
tomography (OCT), a non-invasive test of retinal structure and thickness,
abnormalities of which have been linked to a subset of these disorders.
The proposed longitudinal study will recruit patients presenting with signs suggestive
of PD, PSP, MSA, DLB and CBS (many of whom will have an indeterminate
diagnosis initially) and age-matched healthy controls. Participants will be evaluated
periodically using standardised clinical examinations, cognitive tests and movement
sensor analysis. Blood samples will be analysed by Dr Morrison’s team to assess
mitochondrial function, and a cohort will also undergo genetic tests by Prof
Inglehearn’s team. The OCT scans will be evaluated in conjunction with Mr
McKibbin. It is envisaged that these test results will enable new biomarkers to be
discovered.
This would be a long-term study over at least 7-10 years but there would be enough
data every 2/3 years to form an MD/PhD thesis. Ultimately recruitment would be
opened up to patients with other neurodegenerative conditions.
Investigating the pathophysiology of dystonia
Dr Jane Alty, Consultant Neurologist, LTHT
TBA, neuropsychologist, LTHT
TBA, MRI physicist, University of Leeds
Dystonia is a poorly understood neurological condition that causes involuntary
muscle spasms and twisting postures. It can result in considerable disability and
reduced quality of life. This proposed study would use detailed MRI scans,
neurophysiology, neuropsychological assessments and movement analysis to better
understand the underlying pathophysiology of dystonia and the response to
botulinum toxin injection treatments. Research participants would be recruited from
the large cohort of patients (n=250) who currently attend the dystonia clinics at
Leeds General Infirmary and would undertake assessments before and after their
routine injections.
The changing epidemiology of MS in Leeds and Bradford
Dr Helen Ford, Consultant Neurologist, LTHT
Dr Cord Spilker, Consultant Neurologist, Bradford Teaching Hospitals Foundation
Trust
Mr Roger Parslow, Epidemiologist, University of Leeds
We have previously established population-based registers of people with MS living
in Leeds and Bradford. Recent international evidence suggests significant changes
in the incidence of MS and in the female/male ratio with increasing numbers of
women diagnosed with MS. Our work in Bradford has identified differences in the
clinical presentation of MS in the South Asian population. This may be due to the
effect of different environmental risk factors (Vit D, smoking, diet, EBV, childhood
infections, etc) in South Asian people with MS in Bradford compared to in Pakistan.
Disease modifying treatment for MS may have different efficacy in different groups.
We propose investigating these questions in the combined population of people with
MS in Leeds and Bradford. This will be an in-depth epidemiological study of the
changing incidence and prevalence of MS.
Employment and MS – keeping people with MS in work
Dr Helen Ford, Consultant Neurologist, LTHT
Professor Alan Tennant (Emeritus), University of Leeds
Professor Anna Madill, University of Leeds
People with multiple sclerosis stop working about ten years earlier than expected.
We have developed a measure of the risk of job loss called the Multiple Sclerosis
Work Instability Scale (MS-WIS). This scale has been validated and is now being
used in 7 MS centres in the UK and 5 international centres. We have measured
psychological factors, work instability and the impact of MS in a prospective
longitudinal cohort study of 221 people with MS in paid employment.. Mean age was
40.6 and 75.1% were female. 90.6% had relapsing-remitting MS. 57.2% of
participants were at medium to high risk of job loss. Chi-Square analysis showed
strong associations between work instability and the psychological variables
measured
In this study we aim to design and test a psychological intervention to aid job
retention.
A prospective study investigating predictive biomarkers of epileptogenesis in
patients with major depressive disorder
Dr Melissa Maguire, Consultant Neurologist, LTHT
Dr David Protheroe, Consultant Neurologist, LTHT
Prof Chris Inglehearn, Professor of Molecular Ophthalmology, University of Leeds
There is increasing clinical and experimental evidence to support the existence of a
bi-directional relationship between epilepsy and major depressive disorders.
Epidemiological studies show a four to seven times greater prevalence of primary
psychiatric disorders in new-onset epilepsy than the general population, preceding
the onset of the seizure disorder. In animal models of depression, amygdala kindling
occurs more rapidly when the animal is subjected to conditions of stress. The
development of biomarkers for epileptogenesis may assist in early intervention and
prevention of seizures, thereby preventing SUDEP (sudden unexplained death in
epilepsy) and improving depression and quality of life outcomes.
We aim to explore and identify biomarkers for epileptogenesis in patients with major
depressive disorders. The proposed long-term prospective cohort study will involve
participants undergoing periodic clinical assessment for seizure disorders and
depressive symptoms, structural and functional brain imaging, and blood samples.
Blood will be examined for cortisol levels and genetic testing. Genetics of interest
include polymorphisms of genes encoding the 5HT1a receptor, pro-inflammatory
cytokines and opioid receptor classes: µ-(MOR), - (DOR) and - (KOR).
A randomised controlled trial of SSRIs versus talking therapies in the
treatment of seizures and depressive symptoms in patients with epilepsy
Dr Melissa Maguire, Consultant Neurologist, LTHT
Dr Tom Hughes, Consultant Psychiatrist and Associate Medical Director R&D Leeds
& York PFT
Epilepsy affects around 1% of the UK population. One third of patients with epilepsy
suffer depression. Existing evidence on the effectiveness of anti-depressants and
talking therapies in treating depressive symptoms associated with epilepsy is very
limited. Observational studies provide low quality evidence of safety in terms of
seizure exacerbation, with some studies demonstrating a potential anti-epileptic
effect.
We aim to design a randomised controlled trial (RCT) comparing efficacy of SSRIs
(selective serotonin reuptake inhibitors) and talking therapies in patients ≥16 years
with epilepsy and co-existing major depressive disorder (HAMD depression scale
score >15). The RCT will address the question of comparative efficacy in controlling
depressive symptoms, effect on seizure frequency and also quality of life measures.
We aim to use the innovative true colours data collection tool for collecting and
measuring outcomes.
As part of the trial we aim to sample DNA from participants to explore the impact of
5HT1a receptor gene polymorphisms on clinical presentation and treatment
response. This pharmacogenetic association study may enable a more tailored and
bespoke treatment of depression in patients with epilepsy.