Themes

Spinning down blood samplesThe fourteen Themes detailed here focus on specific groupings of acquired and inherited rare disorders. Although each Theme covers a discrete field of study, all fourteen Theme Leads work closely with one another and the RD-TRC as a whole to create operational synergy and on the creation of a unified strategy designed to deliver our high-level objectives.

In turn, each Theme Lead receives guidance and support on their overall direction and governance from their Theme’s National Working Group, which is also responsible for determining the Theme’s portfolio of studies, sourcing funding, and upholding the RD-TRC’s fundamental values and ethical principles – as well as assuring the health and wellbeing of our volunteers.

Click on the Theme titles below for more information and Theme contact details.

Each theme includes a summary document for the deep phenotyping projects funded by the RD TRC which is available to download.

  • Multiple Endocrine Neoplasia Type 1 (MEN1) and Pancreatic Neuroendocrine Tumours (NETs)

Led by Professor Raj Thakker in Oxford, our first project deals with the rare but potentially fatal group of cancers called pancreatic neuroendocrine tumours including the inherited condition, multiple endocrine neoplasia, which involves genetic mutations in the MEN 1 gene and also affects other organs and sporadic disease (non-MEN 1 disease). Through deep phenotyping of both diseases we aim to better understand their biological behaviour and to use genetic analysis to identify and evaluate new treatments that improve patient care.

This project exemplifies our approach to rare forms of cancer, and over the next 1-2 years we will be adding more examples of unmet clinical need to our portfolio.

Theme

Contact details

Host organisation:
Theme lead: Professor Winette van der Graaf
Theme lead: Professor Tim Meyer
Email: M.Gummadi@rbht.nhs.uk – Mahitha Gummadi (Theme Co-ordinator)

  • Idiopathic and Heritable Pulmonary Arterial Hypertension
  • Sarcomeric Cardiomyopathy
  • Panomic Analysis of Hereditary and Idiopathic Pulmonary Arterial Hypertension

This Theme covers rare, predominantly genetic, disorders of the cardiovascular system including heritable disorders of the heart muscle (cardiomyopathies), inherited arrhythmia syndromes, structural vascular disorders (both systemic and pulmonary) and congenital heart disease. Through better understanding of their genetic aetiology we aim to work towards improved diagnosis, stratification and clinical management, prioritising the collection and phenotyping of cohorts across collaborating centres in diseases where tractable opportunities to develop new therapies are apparent.

Theme

Contact details

Host organisation: NIHR Oxford Cardiovascular Biomedical Research Centre
Prof Hugh Watkins
Theme lead: Professor Hugh Watkins
Email: kathryn.smith@cardiov.ox.ac.uk

  • Autosomal Dominant Parkinson’s disease
  • Motor Neuron Disease (MND)
  • Detailed Phenotyping of Genetic Frontotemporal Dementia for the Development of Clinical Trials

Degenerative diseases affecting the central nervous system are invariably disabling, incurable and complex. There are a large number of individually rare genetic and acquired disorders that can lead to dysfunction of the central nervous system but this Theme currently focuses on rare genetic forms of Parkinson’s disease.

We aim to establish cohorts of genetically tightly defined patients carrying these mutations and those of the many yet-to-be-identified rare genetic disorders that lead to neurodegeneration and at-risk family members patients for deep phenotyping, research and experimental medicine studies.

Theme

Contact details

Host organisation: NIHR University College London Hospitals Biomedical Research Centre
Prof Nicholas Wood
Theme lead: Professor Nicholas Wood
Email: nwoodpa@ucl.ac.uk

  • Stargardt Disease
  • Inherited Optic Neuropathies
  • Characterising Rare iInherited Diseases of the Human Retinal Pigment Epithelium

This theme focuses on detailed retinal functional testing using psychophysics and electrophysiology combined with detailed ocular imaging to explore the effects of specific genetic mutations on retinal and optic nerve function.

We are also one of the few centres in the world using the adaptive optics technology developed in collaboration with the Medical College of Wisconsin, which allows retinal imaging at the level of individual photoreceptors. We are also undertaking studies of the natural history of these rare disorders – providing knowledge that’s vital in planning future clinical trials. Led from Moorfields BRC our studies are part of a multi-centre collaboration with our colleagues in Newcastle, Cardiff, Oxford, Leeds, Cambridge and Manchester.

 

Theme

Further Information

Stargardt Disease

Contact details

Host organisation: NIHR Moorfields Biomedical Research Centre
Theme lead: Professor Graeme Black
Email: graeme.black@manchester.ac.uk
Associate lead: Professor Andrew Webster
Email: samantha.lawrence@ucl.ac.uk

    • Autoimmune Hepatitis (AIH): The UK-AIH Cohort
    • Environmental Phenotyping and Translational Therapeutics in Rare Autoimmune Liver Disease (AILD): The UK-AILD Research Platform
    • Prognostic Modelling in Primary Biliary Cirrhosis using Longitudinal Clinical Data Derived from the UK-PBC Research Cohort
    • The UK Primary Sclerosing Cholangitis (PSC) study: establishing a phenotyped cohort of patients, with the ultimate goal of developing effective therapies

This Theme focuses on rare diseases of the liver and gut that present clinical challenges. At present, our focus is on the rare autoimmune liver diseases primary biliary cirrhosis (PBC), Primary Sclerosing Cholangitis (PSC) and autoimmune hepatitis (AIH), which are important causes of ill-health and death, as well as need for liver transplantation.

Recent successes in liver disease drug therapy, in particular around viral hepatitis, have generated industry interest in other forms of liver disease where there is unmet clinical need. Our cohorts and clinical platforms provide a unique opportunity to work with industry partners to better understand our target diseases and develop, validate and eventually implement, novel approaches to treatment.

Theme

Contact details

Host organisation: NIHR Newcastle Biomedical Research Centre
David Jones
Theme lead: Professor David Jones
Email: miriam.lowes@newcastle.ac.uk

  • Common Variable Immunodeficiency CVID
  • Definition Juvenile dermatomyositis (JDM)

This Theme is dedicated to the exploration of rare diseases affecting human immunological mechanisms, which the range from monogenic immunodeficiency to multifactorial autoimmunity.

Our aims are to define detailed phenotypes alongside next-generation genotypic data, and to stratify treatments in a targeted and personalised manner and to use the new knowledge to development novel diagnostic algorithms and implement of effective therapeutic strategies.

Contact details

Host organisation: NIHR Great Ormond Street Biomedical Research Centre
Prof Adrian Thrasher
Theme lead: Professor Adrian Thrasher
Email: susan.ballard@ucl.ac.uk

  • Ciliopathies; Bardet-Biedl Syndrome and Alstrom Syndrome
  • Congenital Hyperinsulinism (CHI)
  • Type 2 Diabetes in Children
  • Investigation of novel biomarkers and treatment strategies in steroid-resistant nephrotic syndrome and lupus nephritis
  • Clinical and molecular genetic investigation into childhood overgrowth disorders

Because the Paediatric Theme cuts across all others, it has collaborated with the NIHR Clinical Research Network Children specialty and CRF paediatric directors to achieve unanimity in the national paediatric research community, in order to give all UK and Northern Irish children comprehensive, equal and inclusive access to rare disease research.

Led by the Birmingham CRF, the work is facilitated in England by a consortium comprising all NIHR and non-NIHR funded infrastructure (Clinical Research Facilities, Biomedical Research Centres, Bio-medical Research Units, Experimental Cancer Medicine Centres, the Clinical Research Network Children’s specialty) and NHS Highly Specialised Services (previously National Specialist Commissioning Groups).

Contact details

Host organisation: NIHR Birmingham Clinical Research Facility for Experimental Medicine
Prof Timothy Barret-Paedeatric Theme
Theme lead: Professor Timothy Barrett

  • Lysosomal Storage Diseases
  • Segmental Overgrowth due to Mosaicism for Mutations Activating Phosphatidylinositol-3-Kinase Signalling

This theme deals with rare inherited or acquired disorders affecting metabolic homeostasis and/or the endocrine system, such as classical inborn metabolic errors, rarer subtypes of common diseases (eg. obesity or diabetes) and rare endocrine conditions as well as supporting work in the cardiac complications of inherited lysosomal disorders and in the metabolic and other related aspects of regional overgrowth syndromes.

Contact details

Host organisation: NIHR Cambridge Biomedical Research Centre
Prof Sir Stephen O’Rahilly
Theme lead:
 Professor Sir Stephen O’Rahilly
Email: cjs54@medschl.cam.ac.uk

  • Osteogenesis Imperfecta Type 1, 3 and 4

Studying diseases across the life course from birth to late adulthood, this theme deals with inherited and acquired rare disorders affecting bone, joints and blood vessels including skeletal dysplasias/metabolic bone diseases, vasculitides, arthritides and connective tissue diseases, including rare reactions to therapies.

Our multi-disciplinary network of clinical and academic bone disorder and vasculitis specialists, together with a web-based recruitment and assessment database (rudystudy.org) for eligible participants, make for efficient data collection, analysis, diagnosis and accurate allocation of participants to appropriate trials.

Theme

Further information

Musculoskeletal RUDY

Contact details

Host organisation: NIHR Oxford Musculoskeletal Biomedical Research Unit
Theme lead: Professor Bryan Paul Wordsworth
Email: paul.wordsworth@ndorms.ox.ac.uk

  • Inclusion Body Myositis (IBM)
  • Duchenne Muscular Dystrophy
  • Deep Phenotyping the Skeletal Muscle and Peripheral Nerve Channelopathies
  • Inclusion Body Myositis (IBM) – Deep phenotyping to improve diagnostics and treatment

Focusing on rare neuromuscular disorders including inclusion body myositis (IBM), Duchenne muscular dystrophy (DMD) and skeletal muscle and peripheral nerve channelopathies, this Theme aims to improve and standardise natural history data collection in order to harmonise and expand our patient registers.

Working with industry and supporting new trials, this involves deep phenotyping on a national scale to maximise the yield of epidemiological data, increase disease awareness, identify prognostic subgroups, define best outcome measures and, ultimately, to translate research advances into tangible patient benefits and improved patient outcomes.

Contact details

Host organisation: NIHR University College London Hospitals Biomedical Research Centre
Prof Michael G Hanna
Theme lead: Professor Michael G Hanna
Email: n.naeem@ucl.ac.uk

  • Congenital Non-Spherocytic Haemolytic Anaemia (CNSHA)
  • Inheritable factor XI deficiency (FXID)
  • Inherited disorders of platelet number, volume and function with or without bleeding (BPD)
  • Phenotypic and Genotypic Characterisation of Paediatric Myelodysplastic Syndromes

Using our network of paediatric and adult haematologists which, as far as possible, builds on existing specialist networks, this Theme concentrates on diseases with a high likelihood of being caused by high-penetrance DNA variants, most of which present in the first decades of life. As well as work in congenital anaemias, Factor XI deficiency, paediatric myelodysplasia and inherited platelet disorders, the Theme covers disorders such as bone marrow failure syndromes, red cell disorders and rare platelet, bleeding and thrombotic disorders.

Contact details

Host organisation: NIHR Oxford Biomedical Research Centre
Prof Irene Roberts
Theme lead: Professor Irene Roberts
Email: irene.roberts@paediatrics.ox.ac.uk

  • Identifying Biomarkers of IgA Nephropathy Progression

Training Fellowship: Adverse pregnancy and renal outcomes in women with chronic kidney disease: The role of the renin-angiotensin-aldosterone system.

Led from Cambridge but with its two current projects centred in Leicester and at Guy’s, the Rare Renal Disorders Theme is based on a well-developed programme of national working groups in seventeen different conditions/groups of disorders. Each is approved by the UK Renal Association’s Rare Diseases Committee, while running costs are provided by Kidney Research UK.

Formed from ‘bottom up’, these groups include multidisciplinary professional as well as patient representation and have all undertaken to provide online patient and clinician information, and to develop national patient registries moderated through the UK Renal Registry.

Theme

Contact details

Host organisation: NIHR Cambridge Biomedical Research Centre
Prof Fiona Karet
Theme lead: Professor Fiona Karet
Email: fek1000@cam.ac.uk

  • Alpha-1 Antitrypsin Deficiency (AAT)
  • Cystic Fibrosis (CF)

This Theme focuses on rare diseases of the respiratory system, of which approximately 60 have been identified to date including monogenetic disorders such as primary ciliary dyskinesia, diseases with complex aetiology such as interstitial lung diseases, and the rarer manifestation of common diseases such as asthma.

Our first two projects have focused on novel biomarkers for alpha1-antitrypsin deficiency and for cystic fibrosis and the Theme currently includes representation from the NIHR Respiratory Biomedical Research Units (Brompton/Imperial, Southampton, Leicester), respiratory areas from the Biomedical Research Centres (Oxford, Cambridge, UCL, Imperial, Guy’s/St Thomas’/King’s), and Clinical Research Facilities with a respiratory interest (Birmingham, Leeds, Liverpool, Newcastle, Nottingham, Sheffield). There also links with Cardiff, Edinburgh and Belfast.

Contact details

Host organisation: NIHR Royal Brompton Biomedical Research Unit
Theme lead: Professor Eric Alton
Email: m.watson-dotchin@imperial.ac.uk

  • Autosomal Recessive Congenital Ichthyosis (ARCI)
  • Molecular Genetic Analysis of Frontal Fibrosing Alopecia

Although some skin diseases such as eczema and psoriasis are common and affect millions, there are several hundred much rarer ones with diverse aetiologies – developmental, genetic, inflammatory and malignant, which generate a huge health burden – to affected individuals, their families and the state and with considerable impacts on an individual’s physical and emotional well-being.

This Theme therefore focuses on the unique opportunities for translational research created by rare skin diseases’ very visible nature – including deep phenotyping, which contributes significantly to the improvement of patients’ clinical management because it can lead to improved diagnostics and prognostics and stratified clinical trials targeting new therapies to optimally recruited subjects.

Theme

Contact details

Host organisation: NIHR Guy’s & St. Thomas’ Biomedical Research Centre
Prof John McGrath
Theme lead: Professor John McGrath
Email: sandra.grant@kcl.ac.uk