Rare Diseases

Translational Research Collaboration

NIHR Rare Diseases Translational Research Collaboration (RD-TRC)

Funding Request for In-Depth Phenotyping Project Funding

Expression of Interest

Research context: overarching aims of the RD-TRC:

Over 7% of the UK population are affected by one of >5000 different rare diseases, with ~80% being single gene disorders. However, each specific disease is rare, and affects <5 in 10,000 of the population. It is estimated that ~80% of rare diseases are caused by a single gene defect. The overall goal of the RD-TRC is to support in-depth phenotyping of patients with rare diseases, and correlate this to genomic data to provide greater understanding of rare diseases.

Whilst the focus of the RD-TRC is on in-depth pheno-typing, a number of resources are available for acquiring genomic data, including the infrastructure and sequencing capacity provided by the NIHR BioResource – Rare Diseases and Genomics England Ltd. The RD-TRC aims to work with themes to ensure the opportunities for sequencing are fully utilised to exploit synergies across the infrastructure for rare diseases research.

The RD_TRC will support in-depth phenotyping research within a number of themes, each led by a lead within a NIHR BRC / BRU / CRF:

Cancer:Prof. Stan KayeNIHR Royal Marsden BRC

Cardiovascular:Prof. Hugh WatkinsNIHR Oxford BRC

Dementia & Neurodegen.:Prof. Nicholas WoodNIHR UCLH BRC

Eye Disease:Prof. Anthony MooreNIHR Moorfields BRC

Gastrointestinal:Prof. David JonesNIHR Newcastle BRC

Immunological Disorders:Prof. Adrian ThrasherNIHR GOSH BRC

Metabolism:Prof. Stephen O’RahillyNIHR Cambridge BRC

Musculoskeletal Disorders:Prof. Bryan Paul WordsworthNIHR Oxford MSK BRU

Neuromuscular Disorders:Prof. Michael HannaNIHR UCLH BRC

Non-Malignant Haematology:Prof. Irene RobertsNIHR Oxford BRC

Paediatric (Cross-Cutting):Prof. Timothy BarrettNIHR/Wellcome Trust Birmingham CRF

Renal Disease:Prof. Fiona KaretNIHR Cambridge BRC

Respiratory Disease:Prof. Eric AltonNIHR Royal Brompton Respiratory BRU

Skin:Prof. John McGrathNIHR GSST BRC

Criteria for support of in-depth phenotyping of a RD-TRC cohort:

The RD-TRC will provide funding to allow in depth phenotyping for specific rare diseases based on the following criteria:

  • Application endorsed by a NIHR BRC/ BRU or NIHR CRF Director. Any funding awarded will be administered through a variation to a NIHR BRC / BRU / CRF contract.
  • A named lead investigator who has a world-leading track record in rare disease translational research.
  • A clearly articulated, important translational research question with the potential to have impact within 4 years.
  • Evidence from prior knowledge that the research has the potential to advance diagnosis or therapy.
  • Evidence of appropriate existing local clinical infrastructure.
  • Commitment from the lead investigator to develop and use common documentation for consent and information, and to information exchange.
  • The RD-TRC recognises the importance of working with industry in order to successfully deliver health research, development and innovation, and has a strong focus on supporting activity that will foster relationships with industry.

Process

Prospective Investigators are asked to link with the relevant Theme Lead for an initial assessment of their EoI. The Theme Lead, working with the national groups they have established in their rare disease research area, will prioritise up to 4 EoI to be submitted as part of their Theme to the RD-TRC for review by Noon 18th July2014.

Theme Leads will score all submitted EoI and make recommendations to the RD-TRC Co-Chairs as to which EoIs should be invited to submit a full application with detailed costs and a prospective data plan. Deadline for full applications will be the noon 31stOctober 2014.

The process will be iterative and the Themes will work with applicants to ensure their proposals have the greatest possible chance of success at the full application process. Please note that short listing does not guarantee that funding will be awarded.

Funding Types

The RD-TRC will provide project funding for in-depth phenotyping research, typically supporting appropriate research costs including personnel and consumables. Progress against milestones will be reviewed, and failure to progress the project to agreed milestones without satisfactory explanation would lead to withdrawal of funding.

The purpose of this EoI is to identify areas of innovation and opportunity that will translate advances in research into patient benefit. There is no prescribed format and we encourage a diverse range of activity. We are particularly interested in proposals that have identified a partner in industry. If you feel that you can make a significant contribution to the aims of the RD-TRC with regard to in-depth phenotyping, and you have an identified research and/or collaborative opportunity then the RD-TRC would encourage your submission. Applications that build on and extend projects that are currently funded by the RD-TRC will also be considered.Awards of up to £100,000 per annum over two year maximum, will be available starting the 1st April 2015.

Please note the RD-TRC will not fund capital equipment, equipment service contracts and animal work of any description. Indirect NHS costs may be included, though not indirect University costs. NHSSupport Costs should be recovered from your BRC / BRU / CRF, or where sites are not linked to these, via the NIHR Clinical Research Network.

The RD-TRC does not provide funding for genomic studies, but would encourage investigators to seek support from other sources, including NIHR supported infrastructure.

Costing: Approximate cost is required at this stage; however funding will only be awarded once a detailed breakdown has been submitted along with the full application.

Submission: Expressions of Interest should be discussed with the relevant Theme Leads.Theme Leads are requested to submit up to four EoIs for their Theme to: bynoon, 18th July 2014.

NIHR Rare Diseases TRC – Currently funded disease areas

Cancer

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

Cardiovascular

•Idiopathic and heritable pulmonary arterial hypertension

•Sarcomeric cardiomyopathy

•Hereditary and Idiopathic Pulmonary Arterial Hypertension

Dementia & Neurodegenerative (UCLH BRC)

•Autosomal Dominant Parkinson's disease

•Motor neuron disease (MND)

•Genetic frontotemporal dementia

Eye Disease

•Stargardt disease

•Inherited optic neuropathies

•Retinal pigment epithelium

Gastrointestinal

•Autoimmune Hepatitis (AIH): The UK-AIH Cohort

•Rare Autoimmune Liver Disease (AILD)

•Primary Biliary Cirrhosis

Immunological Disorders

•Common Variable Immunodeficiency (CVID)

•Definition Juvenile dermatomyositis (JDM)

Metabolism

•Lysosomal Storage Diseases

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

Musculoskeletal Disorders

•Osteogenesis imperfecta type 1, 3 and 4

Neuromuscular Disorders

•Inclusion Body Myositis (IBM)

•Duchenne muscular dystrophy

•Skeletal muscle and peripheral nerve channelopathies

•Inclusion Body Myositis (IBM)

Respiratory Disease

•Alpha-1 Antitrypsin Deficiency (AAT)

•Cystic fibrosis (CF)

Skin

•Autosomal Recessive Congenital Ichthyosis (ARCI)

•Frontal Fibrosing Alopecia

Paediatric Cross Cutting

•Ciliopathies; Bardet-Biedl Syndrome and Alstrom Syndrome

•Congenital Hyperinsulinism (CHI)

•Steroid Resistant Nephrotic Syndrome (SRNS)

•childhood overgrowth disorders

Non-Malignant Haematology Disorders (NMHD)

•Paediatric Myelodysplastic Syndromes

Renal

•IgA nephropathy

•chronic kidney disease (CKD) in pregnancy

RD-TRC

Expression of Interest

RD-TRC Reference: ...... (admin use only)

Principal Investigator
Name......
E-mail......
BRC / BRU / CRF......
………………………………………………………………………….
Full Title of Study
Alternative ‘Short’ Title (no more than 20 characters)
Please indicate one major theme and any related themes that your project aligns to
Theme(s)
Patient Group to be studied
Sample Size
Proposed start date
Proposed end date
Related Theme(s)
Research Summary (not more than 200 words)
Please provide a summary of your project and the research question it will address
Track Record and opportunities to link this work with Industry if appropriate (not more than 100 words)
Please provide a summary of any experience of working with industry
Evidence of Public and Patient Engagement(not more than 100 words)
Resource (funding) Requested (Approximate annual costs)

Signature Applicant Signature Theme LeadSignature BRC/BRU/CRF Director

Name: Name: Name:

Date:Date:Date:

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