Neurological diseases

Medical Research Scotland is one of the largest and most comprehensive independent research charities in Scotland. Unlike most medical research charities, our funding isn't restricted to any one disease or condition, we support high-quality research that aims to improve the understanding, diagnosis, treatment and prevention of all diseases and disease mechanisms.

Awards in the past 20 years

The following are some of the awards we made for research into diseases affecting the brain and neurological system, including stroke.

Dr Elaine Hunter (Institute of Neuroscience and Psychology, University of Glasgow) supervised by Dr Stuart Cobb and Dr. Mark Bailey during her Medical Research Scotland sponsored Daphne Jackson Trust Fellowship, "Metabolic resilience of neuronal activity in a mouse model of Rett Syndrome"
Rett syndrome (RTT) is a leading cause of severe disability in girls affecting 1 in 10,000 female births. >95% of girls with RTT have a mutation in the DNA of one gene, methyl-CpG-binding protein 2 (MeCP2), and mouse models have been developed to study this disease. MeCP2 mutations reduce a cell’s ability to make proteins; particularly those proteins involved in energy production within the mitochondria. This study will investigate whether mutations in MeCP2 cause a functional change in the ability of mitochondria to make energy in normal and RTT animals by measuring the amount of oxygen consumed by isolated mitochondria. In the brain, nerve cells which release the neurotransmitter GABA are the main system which calms electrical activity and regulates breathing rhythms. These GABAergic neurons are very active and have high energy demands. We will compare the electrical and mitochondrial activity of individual GABAergic neurons in RTT, to investigate whether their higher energy demands make them more sensitive to MECP2 mutation. This could provide a common cellular pathway linking the various neurological symptoms seen in RTT and open up a series of novel targets for drug development for the symptomatic treatment of the disorder.

Dr Alasdair MacKenzie (School of Medical Sciences, Aberdeen University) to supervise Ms Elizabeth Hay during her PhD Studentship, "The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy." This research will also involve close working with GW Pharmaceuticals.
The cannabinoid-1 receptor protein (CB1) has been implicated in obesity, addiction and chronic inflammatory disease and represents an excellent drug target for their treatment. However, promising drugs designed against CB1 can cause unacceptable side-effects in a proportion of patients. Little evidence exists that mutations in the gene that makes CB1 are involved in disease progression or drug side effects. Could mis-regulation of the CB1 gene be to blame? We have shown that obesity and addiction associated mutations alter genetic control switches required to regulate the healthy expression of the CB1 gene. We also show that activating the CB1 protein activates these switches, demonstrating self-regulation, but that disease-associated mutations disable these control switches. These mutations also change susceptibility of the switches to epigenetic modification; a process influenced by early life events. We will further investigate the switches that regulate the CB1 gene in brain regions that control inflammation and appetite where we believe genetics and the environment interact to influence disease susceptibility and drug-side effects. This project will also test novel drug treatments in development by GW Pharmaceuticals to manipulate these switches aiming to accelerate the development of personalised cures for inflammatory diseases, addiction and obesity.

logo Professor Susan Barnett (Institute of Infection, Immunity & Inflammation, Glasgow University) will be supervising Sara Hosseinzadeh during her PhD Studentship, "Development of polymer scaffolds for use in the repair of spinal cord injury". This research will involve close working with Spheritech.
Spinal cord injury (SCI) is a major cause of persistent disability. One promising therapeutic approach is cell transplantation to fill the damaged injury site and encourage nerve processes to fill the gap. A range of neural/stem and engineered cells have provided tested evidence that this is a plausible approach in animal models of SCI. Although cell transplants can provide a environment conducive to axonal regeneration, however, the resulting axonal growth is poorly organised and this approach will not be possible where physical disruption of the spinal cord is extensive. Further, as growth of human cells in culture can be slow and it is technically challenging to grow the large numbers of cells needed to fill a human lesion, we would like to develop an artificial scaffold seeded with glial cells to bridge the gap and promote repair. The main aim of the project is to test whether novel super-macroporous polymer scaffolds invented by Spheritech and designed to promote well-organised and appropriately aligned axonal growth can support the growth and differentiation of central nervous system cells as a prerequisite for use in vivo. This project will allow us to validate the scaffolds using our cultures that mimic the intact CNS environment prior to using animal models.

Dr Andrew Sutherland (School of Chemistry, Glasgow University) to supervise Nikki Sloan during her PhD Studentship "New Metal Catalysed Methods for the Efficient, Non-toxic Generation of PET and SPECT Tracers: Molecular Imaging of Neurological Disease". This research will also involve close working with GE Healthcare.
Radionuclide molecular imaging is increasingly used for the early diagnosis of both neurological diseases and cancer. However, the widespread application of this technology is being limited due to current methods of generating the imaging agents which can involve unstable, highly toxic precursors. In collaboration with GE Healthcare, this project will investigate new transiton metal-catalysed chemical processes that will allow simple, easy access to PET and SPECT tracers from readily available, non-toxic starting materials. In particular, the project will investigate the use of nickel catalysts for the incorporation of radiohalogens into aromatic compounds, structural motifs that are found extensively in molecular tracers. On development of each new reaction, the versatility of this process will be demonstrated by the preparation of molecular tracers used in the imaging of cancer and neurological disorders, particularly Alzheimer's disease. Discovery and successful development of these new chemical transformations for the non-toxic and facile preparation of PET and SPECT imaging agents will accelerate the application of this technology across the NHS and the pharmaceutical/life sciences industries.

Dr Berndt Mueller (School of Medical Sciences, Aberdeen University) to supervise Miss Jihan Anderson during her PhD Studentship "Identification and correction of the molecular and cellular defects in neurons caused by deregulation of the novel autism susceptibility gene EIF4E - an opportunity to develop treatments for autism". This research will also involve close working with Dundee Cell Products.
Autism is an as yet untreatable but common lifelong childhood-onset neurodevelopmental disorder affecting 1 in 200 individuals. The underlying genetics is complex and poorly understood. We have identified EIF4E as an autism susceptibility gene. In addition, mutations in several genes known to control the activity of eIF4E protein cause autism or syndromes with autistic features. Together, this strongly supports our hypothesis that over-expression of eIF4E protein predisposes to autism and we propose that correction of eIF4E over-expression could form the basis of effective treatment of autism. To test this we will identify the abnormalities caused by eIF4E over-expression in neurones using two complementary approaches: we will determine the effect of eIF4E over-expression on the differentiation and behaviour of neurones using live-cell microscopy and immunocytochemistry, and we will identify changes in protein components caused by eIF4E over-expression using state-of-the-art protein profiling methods. Together, this will increase our understanding of the underlying molecular events leading to the development of autism. We will produce reagents for the detection of proteins whose levels are changed, as they may serve as marker proteins for autism. Finally, we will test whether any changes occurring in neurones when eIF4E is over-expressed can be reversed by compounds known to control eIF4E activity. This work will produce reagents to identify subjects with autism caused by dysregulation of eIF4E and will lead to screens that are expected to identify novel compounds to treat this condition.

Professor Colin Campbell (School of Chemistry, Edinburgh University) to supervise Miss Hannah Johnston during her PhD Studentship, "Systems redox biology analysis of a novel family of naturally-derived anti-oxidants/anti-inflammatories". This research will also involve close working with Aquapharm BioDiscovery Ltd.
The regulation of cellular redox potential is important in controlling the behaviour of healthy cells and its dysregulation is implicated in the initiation and proliferation of several disease states. Redox potential is a measure of the driving force for oxidation and oxidative changes are known to be important in the initiation or proliferation of a variety of diseases including arthritis, chronic obstructive pulmonary disease (COPD), Alzheimer's disease, age-related macular degeneration and multiple sclerosis. Aquapharm Biodiscovery Ltd. has recently discovered a new family of molecules which have therapeutic potential as anti-oxidants or anti-inflammatory drugs in diseases such as those listed above. It is thought that this family of molecules works by interacting with pathways involved in cellular redox regulation. Our aim in this project is to use a combination of cutting-edge biophysical techniques, established molecular biology assays and a new approach to visualisation and interpretation of this data to understand the mode of action of Aquapharm's therapeutic molecules with a view to optimising their effect. Through combining quantitative measurements with a systems biology approach we will produce a quantitative map of redox potential distribution in the cell that offers a completely new way to analyse the effects of molecules which alter redox-regulation.

£149,790 over three years to Dr Leanne McKay (Institute of Neuroscience & Psychology, Glasgow University), to study the development and maturation of the neural control of breathing.
Respiratory control disorders like sleep apnoea and sudden infant death syndrome are very common, but their origins are not well understood. A better understanding of how the brain generates the nerve signals that produce respiratory rhythm is crucial if ways are to be found to treat or prevent these disorders. This project aims to provide valuable new information about the mechanisms underlying development and maturation of the respiratory system.

£149,855 over three years to Dr Louise S. Bicknell (Institute of Genetics & Molecular Medicine, Edinburgh University) for a project which seeks to uncover the genetic causes of primordial dwarfism, harnessing gene discovery to gain insights into how humans grow.
Primordial dwarfism is a genetic disorder leading to a maximum adult height of only 1 metre. Identifying the cause of such disorders is important for both patient care and reproductive choices for family members. Many different genes are known to underlie the condition, so identifying them could provide insight into how human growth is controlled. This project will use cutting-edge genetic technology to identify the genetic changes in these patients and to study them in detail, to learn more about the dynamics and regulation of cell growth.

£148,872 over 36 months to Dr Richard Mort & Professor Iain Jackson (Medical & Developmental Genetics, MRC Human Genetics Unit, Edinburgh) & Dr Kevin Painter (Mathematics, Heriot-Watt University), to take an integrated multidisciplinary approach to modelling normal neural crest cell development and the abnormalities that contribute to human birth defects.
1 in 3,000 babies born in the UK are diagnosed with neurofibromatosis type 1 (Nf1). As well as having an increased risk of developing cancers of the nervous system, >95% of children diagnosed with Nf1 also have variable amounts of skin and hair hyper- or hypopigmentation. Pigment cells are a subtype of neural crest stem cells (NCSCs), the migration of which is a fundamental antenatal development process. Using a unique integration of live imaging and mathematical modelling, this project aims to explain neural crest cell behaviour in these and related disorders.

£141,848 over 30 months to Dr Hui-Rong Jiang (Institute of Pharmacy & Biomedical Sciences, Strathclyde University), to investigate IL-33 activity in the development of neurological autoimmune diseases.
Multiple sclerosis (MS), a chronic disease which causes irreversible damage to the central nervous system (CNS), is the leading cause of non-traumatic neurological disability among young adults and its prevalence in Scotland is one of the highest in the world. There is currently no cure and existing treatments are largely ineffective. MS is an autoimmune disease in which cell-signalling proteins called cytokines play an important part. This project aims to improve understanding of the role of cytokine IL-33 in the development of MS and other neurological diseases by clarifying its role in modulating immune responses and CNS repair.

£149,861 to Dr Bing Lang & Professor Colin D. McCaig (Institute of Medical Sciences, Aberdeen University) and Dr Colin Smith (Pathology, Western General Hospital, Edinburgh), for a three-year project aiming to uncover novel biomarkers for schizophrenia.
Schizophrenia and bipolar disorder affect 1 in 50 people. No effective medication is available and current antipsychotic drugs often have unpleasant side-effects. This project aims to explain aspects of abnormal brain development in schizophrenia and identify new biomarkers which may be useful in future drug development.

£141,343 over three years to Dr Gareth B. Miles (School of Biology, University of St Andrews), to test the 'synaptic stripping' hypothesis for amyotrophic lateral sclerosis (ALS), by an investigation of cholinergic synapses on motoneurones in ALS.
ALS is a neurodegenerative, paralysing and fatal disease which results from the selective loss of motoneurones - the nerves in the brain and spinal cord responsible for controlling movement. It is incurable and the only available treatment has limited benefit. This project hopes to shed light on the poorly understood mechanisms which damage the nerves.

£74,715 to Dr Jenni Harvey (Neurosciences Institute, University of Dundee) for a two-year investigation of whether age-related decline in cognitive function is assocated with altered neuronal responsiveness to leptin.
Leptin regulates food intake and body weight and is also involved in the processes underlying learning and memory. Food intake is linked to age-related cognitive decline; over-eating increasing the risk. The levels of brain leptin receptors reduce with age and this research will investigate whether age-related decline in cognitive performance and brain leptin function are linked.

£79,111 to Dr Trevor John Bushell (Physiology & Pharmacology, University of Strathclyde) for a two-year project to determine the role of proteinase-activated receptor 2 upregulation in CNS neurones.
This study aims to understand the part played by proteinase-activated receptors in communication between nerve cells in the central nervous system, information that is key to the development of treatments for diseases such as multiple sclerosis, Alzheimer's and Parkinson's.

£79,816 to Dr Julie Calvert (Vision Sciences, Glasgow Caledonian University) & Professor Gordon Neale Dutton (Royal Hospital for Sick Children, Glasgow) for a two-year project on the identification, characterisation and management of dorsal stream dysfunction in children.
Many children with early brain damage have complex visual problems which may result from damage to the nerve pathway which processes information on the spatial properties and motion of objects. This project aims to develop a test to identify affected children as early as possible, to avoid their educational and social development being impaired.

The Medical Research Scotland/Mrs Jean V. Baxter Medical Research Fellowship 2006-08 was awarded to Dr Marie-Astrid Pezze (Centre for Cognitive & Neural Systems, University of Edinburgh) for her project entitled "Dopamine signalling from the ventral tegmental area to the hippocampus, novelty, and memory encoding: investigating the substrates of cognitive deficits in schizophrenia".
This work will identify possible links between the effects of current treatments for, and the memory impairment associated with, schizophrenia.

£69,971 over two years to Dr Thomas Gillingwater (Anatomy, University of Edinburgh) for high-resolution imaging of synapse loss in mouse models of spinal muscular atrophy.
The junction between nerve and muscle is a primary site of damage in spinal muscular atrophy, one form of the degenerative and ultimately fatal condition known as motor neurone disease. This study will investigate the detail of the anatomical changes occurring in the cells of the junctions between the nerves and the muscles in the disease.

£79,820 to Dr Giles E. Hardingham (Preclinical Veterinary Sciences, Edinburgh University) for a two-year investigation into neuronal pro-survival pathways triggered by the synaptic activation of NMDA receptors.
Nerve cells communicate with each other by chemical signals, detected by receptors. One such receptor, NMDA, causes signal activation which seems to keep neurones alive. This project proposes to study these 'pro-survival' signals, whose effects are depleted in brain diseases such as Alzheimer's and Huntington's and also in other forms of brain damage, such as is caused by strokes.

£79,982 to Dr Sanbing Shen (Biomedical Sciences, Aberdeen University) for a two-year investigation of the cellular and molecular mechanisms of neural tube defects.
By studying the activity of two enzymes found in the developing brain, this progect aims to establish if, in inappropriate quantities, they are a cause of neural tube defects such as spina bifida.

£79,644 to Dr Fiona A. White (Division of Clinical Neurosciences, Glasgow University) for a two-year project for the assessment of GADD34 as a potential therapeutic target in cerebral ischaemia.
This work aims to improve understanding of the molecular and cellular processes involved in the damage to brain cells which can result in stroke.

£63,236 over 18 months to Dr Neil McLennan & Professor David W. Melton (Molecular Medicine Centre, Edinburgh University) to study the role of the prion protein in protecting the brain from oxidative stress. Oxidative stress is known to cause damage to neurones in diseases such as Parkinson's.
This research seeks to establish if prion proteins have a role in protecting neurons from oxidative stress, which would protect the brain and its functioning.

£ 64,995 over two years to Dr James M. Brewer (Division of Immunology) and Drs Clive Bate & Alun Williams (Veterinary Pathology, Glasgow University) for an analysis of the role of cholesterol-sensitive domains in the trafficking and neurotoxicity of prions.
Prion diseases,such as CJD and BSE, cause death and dysfunction of neurones through mechanisms which are not fully understood. This study will look at the role of cholesterol-rich areas on neurones to establish if high levels of cholesterol are needed by prions to exert their destructive effects.

£57,838 over two years to Dr Gayle H. Middleton (Preclinical Veterinary Sciences, Royal (Dick) Vet School, Edinburgh University) to investigate the role of the Bcl-2 protein family in regulating cell survival in the substantia nigra and striatum.
Neurodegenerative diseases, such as Parkinson's & Huntington's, involve an imbalance of the molecules promoting brain cell death and those preventing it. This research focuses of the Bcl-2 molecule family to understand their role in these processes.

The Nasmyth Travelling Research Scholarship 2000-2002 was awarded to Dr Tracey A. Baird (Neurology, Southern General Hospital, Glasgow) to visit the Department of Neurology, Royal Melbourne Hospital and the Centre for Brain Imagine Research, Austin & Repatriation Medical Centre, Heidelberg, Victoria, Australia. The focus of Dr Baird's research is to find new, simple and cost-effective ways to diagnose and treat acute stroke - a disease which remains the third commonest cuase of dealth in Scotland.

£69,957 over three years to Dr Frank J. Gunn-Moore (School of Biology, St Andrews University) to investigate the amyloid-ABAD complex, a novel model for Alzheimer's Disease.
The protein amyloid is known to be deposited in the brains of patients with Alzheimer's disease, where it is thought to bind to ABAD protein. This research will study the molecular effects of deposition and look at the early processes in Alzheimer's.

£99,418 over three years to Drs Andrew J. Irving and Bruno Frenguelli (Pharmacology & Neuroscience, Dundee University) for a study linking hypoxia/ischaemia with altered glutamate receptor expression and dynamic changes in the neuronal cytoskeleton.
Neurodegeneration following reduced blood flow and oxygen deprivation involves the production of certain receptor complexes which are activated by glutamate, intensifying the damage. By studying these neurotoxic receptors this research hopes to find a way to modify the neurone damage and prevent loss of normal functioning.

£31,293 over three years to Dr Stuart R. Cobb (Neurosience & Biomedical Systems, Glasgow University) to investigate the role of nicotinic acetylcholine receptors in controlling epileptiform activity.

£62,411 over 18 months to Dr Christine Bell, Ms Caroline Clark & Professor Neva E. Haites (Medical Genetics, Aberdeen University) to investigate the role of regulatory sequences of the candidate genes in the pathogenesis of hereditary motor and sensory neuropathy Type 1 (HMSN1).

£68,457 over two years to Dr Stephany M. Biello (Psychology, Glasgow University) for a study of the neural basis of circadian timing.

£84,954 over two years to Dr Gurman Pall, Professor Keith Johnson & Dr Catherine Winchester (Molecular Genetics, Glasgow University) for the identification and characterisation of the genes regulated by the homeodomain protein SIX5 and their contribution to the pathogenesis in myotonic dystrophy.

£40,695 over one year to Drs Alasdair M.J. MacLullich (Molecular Endocrinology Unit) & Joanna M. Wardlaw (Clinical Neurosciences) and Professors Jonathan R. Seckl (Molecular Endocrinology Unit) & Ian J. Deary (Psychology, Edinburgh University) to investigate the relationshp between hippocampal structure, metabolites, glucocorticoids and age-related cognitive decline by means of an mri and spectroscopy study.

A Medical Research Scholarship 1999-2000 was awarded to Dr Susan Kerr (Aberdeen Royal Infirmary) to study the effect of nitric oxide donation on regional cerebral blood flow and metabolism in acute ischaemic stroke

£70,000 over two years to Dr Keiran C. Breen (Pharmacology, Dundee University) to continue his research into the role of tau protein glycosylation in the generation of neurofibrillary tangles associated with Alzheimer's Disease.

£69,674 over two years to Dr Peter D. Currie (Human Genetics Unit, Edinburgh University) for the identification of downstream mediators of the secreted signalling moelcule Sonic Hedgehog.

£33,671 over one year to Dr Colin D. McCaig (Biomedical Sciences) & Professor John V. Forrester (Ophthalmology, Aberdeen University) to investigate sprouting nerves and healing cornea.

£30,415 over one year to Dr Malcolm P. Caulfield (Pharmacology & Neuroscience, Ninewells Hospital & Medical School, Dundee) for a study of metatropic glutamate receptors in cerebellar Purkinje neurones.

The Mrs Jean V. Baxter Medical Research Fellowship 1997-1999 was awarded to Dr Alasdair M.J. MacLullich (Rehabilitation Medicine, Astley Ainslie Hospital, Edinburgh) for a study of the association between glucocorticoids and brain ageing.

£99,697 to Dr Bruno Frenguelli (Pharmacology, Ninewells Hospital & Medical School, Dundee) for a three-year investigation into neuronal function after hypoxia/ischaemia in the in vitro rat hippocampal slice.

£94,237 to Dr Ian J. Holt (Molecular & Cellular Pathology, Ninewells Hospital & Medical School, Dundee) & Dr Alan R. Prescott (Biochemistry, Medical Science Institute, Dundee University) for a three-year project analysing innervated cultured muscle from patients with mitochondrial disease.

£25,963 to Dr Deborah Dewar (Wellcome Surgical Unit, Glasgow University) for a one-year in vitro study using organotypic slice cultures of presynaptic protein damage after ischaemia.

£85,285 to Mr Robert P. Mills (Otolaryngology, Ninewells Hospital & Medical School, Dundee) and Dr Eric W. Abel (Biomedical Engineering, Dundee University) for a two-year in vitro evalulation of physiological models of the ossicular chain.

£63,539 to Dr Malcolm P. Caulfield (Pharmacology & Clinical Pharmacology, Ninewells Hospital & Medical School, Dundee) for a study to define the transduction pathways inducing long-term synaptic depression and release of calcium from intracellular stores by investigating the metabotropic glutamate receptors in cerebellar Purkinje neurones.

£56,145 to Professor Janet M. Allen (Biochemistry & Molecular Biology, Glasgow University) for a study of neuronal differentiation induced by the neuropeptide pituitary adenylyl cyclase activating peptide (PACAP).

£36,063 to Dr Karen Horsburgh (Wellcome Surgical Institute & Hugh Fraser Laboratories, Glasgow University) for a one-year study of alterations in protein kinase C and amyloid precursor protein in human head injury and stroke.

£19,211 to Drs Richard Ashley & Cecile Martin (Biochemistry, Edinburgh University) and Dr Karen Chapman (Medicine, Western General Hospital, Edinburgh) for a six-month pilot study of the expression of calcium release channel genes in human brain.

£89,854 over three years to Dr Kieran C. Breen (Pharmacology & Clinical Pharmacology, Dundee University) for a study of neural glycosylation state in Alzheimer's Disease.

£89,850 over two and a half years to Drs Hugh J. Willison & G. Paterson (Neurology, Glasgow University) and colleagues in Cambridge, London and Texas, for a study involving combinatorial library cloning of anti-ganglioside antibodies from autoimmune neuropathy patients.

The Mrs Jean V. Baxter Medical Research Fellowship 1993-95 was awarded to Dr Karen J. Horsburgh (Wellcome Surgical Institute & Hugh Fraser Laboratories, Glasgow University) for work on protein kinase and beta-amyloid protein deposition in human head injury and stroke.