Publication - Progress report

Rare Disease Scotland: progress report

Published: 28 Feb 2018

An update on the work carried out in Scotland against the 51 Commitments in the UK Strategy for Rare Diseases.

83 page PDF

1.6 MB

83 page PDF

1.6 MB

Rare Disease Scotland: progress report
5. Research (31 – 51)

83 page PDF

1.6 MB

5. Research (31 – 51)




Look at how the four UK countries develop, change or expand information systems to capture, connect and analyse data about clinical and social care pathways.


Work together to identify a selection of rare diseases most suited to the development of best-care pathways and propose other rare diseases for possible pathway development, taking on board the needs of patients and carers and the challenges faced during delivery of the first set of pathways.


Examine how they can encourage service providers to involve patients in research and to ensure appropriate funding for excess treatment costs for research in rare diseases.


Make better use of online applications to give patients information about their condition so that they can develop a personalised care path plan with their clinical and social care team.


Use portals to connect patients and relatives to enhance research participation and, where appropriate, promote self-enrolment to approved research studies with online consenting, self-reporting and use of social media.


Encourage patient groups to get involved with regulatory bodies.


Help patient organisations and community engagement events develop more formal partnerships with the NHS research-active organisations.


Explore the feasibility of the UK Clinical Trials Gateway including experimental medicine trials for rare diseases to provide information for patients and their families about research trials.


Work with the research community, regulators, providers of NHS Services and research funders to develop risk-proportional permission systems.


Encourage researchers to use current guidance to produce generic participant information leaflets and consent forms and participate in future guidance reviews.


Promote good practice and the use of systems which facilitate a consistent and streamlined process to local NHS permissions of publically, charitably and commercially funded research with an aim to reduce timescales.


Begin and complete next generation sequencing ( NGS) demonstration projects to: evaluate their usefulness, acceptability and cost-effectiveness; develop effective health economic assessments (for example through Health Technology Assessments) and similar initiatives.




Evaluate the different NGS platform configurations, for example:

  • NGS for clinical condition-specific sets of genes (such as 100-200 of the 22,000 genes);
  • whole exome sequencing (2% of the entire genome); and
  • whole genome sequencing.


Support the introduction of NGS into mainstream NHS diagnostic pathways, underpinned by appropriate clinical bioinformatics, including clinical bioinformatics hubs supported by high performance computing centres, where appropriate.


Ensure that training and education are available to the NHS workforce, highlighting the importance of NGS to all aspects of rare disease care, including the support for evidence-based local counselling for patients and their relatives who receive NGS results.


Work with industry to set priorities and determine how best to support research into rare diseases and promote research collaboration.


Support initiatives to facilitate engagement between patients, clinical care teams, researchers and industry wherever practical.


Set out the benefits of collaboration (besides producing specific treatment) for all stakeholders.


Continue to build a cohesive infrastructure for implementation and coordination of rare disease research in the NHS.


Encourage major research funders to use current structures to coordinate strategic funding initiatives in rare diseases.


Improve engagement between key stakeholders, including:
a. patients and relatives
b. main funding providers
c. healthcare commissioners
d. NHS hospitals and specialist care units
e. industry (pharmaceutical, biotechnology, IT, diagnostics).


SHARE [43] is a new NHS Research Scotland [44] initiative created to establish a register of people interested in participating in health research who agree to allow SHARE to use the coded data in their various NHS computer records to check whether they might be suitable for health research studies. This access can be incredibly useful when it comes to developing new treatments and cures for a wide variety of health conditions.

SHARE aims to have 1 million people registered by 2023, there are currently over 188,000 people registered.

Work has started on raising awareness in the Rare Disease community, and the existence of SHARE has been communicated to the Scottish network within Genetic Alliance UK.

SHARE has also recently started publishing live studies. People can read about the study, and if they are interested in participating can enter their details into the assessment questionnaire, and it will tell them immediately if they are able to participate.

More information is available on the website:

SHARE addresses Commitments 7, 35, 37, 48, 49 and 50 of the UK Strategy for Rare Diseases.

5.2 The Scottish Genomes Partnership

The Scottish Genomes Partnership ( SGP) [45] was established in January 2015, with a £15m investment from the Universities of Edinburgh and Glasgow. Ten state-of-the-art Illumina HiSeq X genome sequencing instruments were installed at their sequencing hubs. These are Edinburgh Genomics and the Translational Research Centre at the Wolfson Wohl Cancer Research Centre.

In February 2016, the SGP received £6m in research funding from Scotland’s Chief Scientist Office (£4m) and the UK’s Medical Research Council (£2m), This created a Scotland-wide research partnership to pioneer precision medicine and human genome discovery through academic, NHS clinical and industrial collaborations. The aims of the partnership are to:

  • Test the utility of whole genome sequencing for (a) diagnosis of rare diseases and (b) clinical trial stratification for cancers.
  • Add value to Scotland’s strengths in genomic medicine and science, building a strong foundation for health and wealth creation.
  • Expand Scotland’s capacity to lead national and international collaborations in human genomics.
  • Provide a supportive environment for Scottish academics, SMEs and industry to engage in genomics and bioinformatics research.

The 100,000 Genomes Project
In March 2017, the SGP Rare Disease collaboration with Genomics England 100,000 Genomes Project [46] opened for recruitment. One thousand participants will be recruited through the nationally designated NHSScotlandgenetic clinics in Aberdeen, Dundee, Edinburgh and Glasgow by the end of March 2018.

The SGP-NHSScotlandcollaboration with the rare disease arm of the 100 Genomes Project has been established with the direct aim of providing evidence to inform the future delivery of NHS genetics services. SGP is contributing 1,000 genomes to the project from patients with rare diseases and their family members to investigate the extent to which Whole Genome Sequencing could improve genetic diagnosis and clinical follow-up for rare disease patients in Scotland. Through this research, genomics services in Scotland are working with clinical genomics researchers in England, Northern Ireland and Wales. This ensures that Scottish patients will benefit from a UK-wide approach to the analysis of WGS, improving rare disease genetic testing and clinical follow-up for patients.

The SGP describe the study as follows:

“NHSScotlandGenetics Services will identify potential participants and their families, manage the consent process, collect samples and data, extract DNA and provide de-identified data on participant symptoms to Genomics England. The Universities of England and Glasgow will carry out Whole Genome Sequencing on de-identified DNA samples, before sequence data are sent to Genomics England from the Edinburgh Parallel Computing Centre. Genomics England will analyse variants in the Scottish Genome data alongside the data in the 100,000 Genomes Project, to enable comparisons to be made of symptoms and genomic variants across the dataset. Analyses will continue in the future as more data is obtained from genetics centres around the UK. NHSScotlandGenetics Services will check results received from Genomics England, and provide feedback and clinical results to participants. Clinical management will be carried out within the NHS in the normal way.”

As part of the SGP, the NHS National Services Division, which is responsible for commissioning and performance managing Genetics and Molecular Pathology Laboratory services in Scotland, has been leading an alliance of Health Boards across Scotland to facilitate joint working between academic researchers, the four regional clinical Genetics units and four nationally-commissioned Genetic laboratories. A Memorandum of Understanding and Data Sharing Agreement with Genomics England have been put in place to formalise these arrangements.

Intensive working between January 2016 and February 2017 was required to align the Scottish protocol with the Genomics England approach, as well as gaining regulatory approvals from the Public Benefit and Privacy Panel for Health and Social Care and NHS Research Scotland.

With the approval in place, the SGP Rare Disease collaboration with the 100,000 Genomes Project opened for recruitment in March 2017.

Participants are approached by clinical geneticists who will ensure that the participation criteria are met. Potential participants must:

  • Have clear evidence of a genetic or family condition which has not been diagnosed through existing test.
  • Be part of a family group, which is important for genetic analysis.
  • Be eligible according to the list of agreed rare disorders specified by Genomics England.
  • The test result will have clinical utility for the patient and/or their family.

The first set of reports from Genomics England are expected back to regional genetic laboratories around December 2017, with reporting back to all participants completed by the end of February 2019.

Rare Disease Research Projects

The SGP Rare Disease academic studies build on Scotland’s outstanding academic track record in gene identifications and functional analysis of single gene human disorders. Four SGP academic-led studies are underway at the Universities of Edinburgh and Glasgow, which focus on molecular influences on motor neurone disease, eye malformation, microcephalic dwarfism and disorders of sexual development. While these are academic-led studies, the Principal Investigators are all part of Multi-Disciplinary Teams which review local clinical cases, and so the learning from all of these studies will be directly transferrable into clinical decision making. The sequencing of around 800 genomes for these studies is 80% complete, with initial analyses underway prior to the selection of final cases.

SGP Programme developments

Members of the SGP’s internationally respected Scientific Advisory Board have commended the exceptional high quality of the on-going work, and noted the cohesive nature of the cross-Scotland working on cutting edge issues of clinical and biological relevance. At its meeting in April 2017, the Board made several recommendations for going forward, which are relevant to the Scottish Rare Disease Implementation Plan.

  • Develop a single Scottish genome archive. Ensuring that the data collected or generated across the different work streams is integrated and broadly available for clinical and research use as possible, including developing IT tools and infrastructure to facilitate and empower access to the data.
  • Achieving further integration across Scotland. Capitalising on the opportunities for working together within a small geographical area for rare disease genetics research.
  • Inform downstream delivery of healthcare and future services. Considering the way in which genomics will be used to deliver healthcare in the future, including commissioning of services, training the workforce in analysis and interpretation of WGS data, and collection of appropriate data to assess usefulness and cost-effectiveness of WGS for diagnosis, treatment and counselling in families affected by rare diseases.
  • Engage the public in genomics. Advancing understanding and promoting participation are key to future research and genomically-informed care.

The SGP have considered and are now acting on these recommendations.

The work of the SGP addresses Commitments 29, 42, 43, 44, 45, 47, 49 and 50 of the UK Strategy for Rare Diseases.

Patient Involvement in Research Scotland and the rest of the UK are leaders in research into rare conditions. Partnership and collaboration with patients and patient groups in developing research initiatives is necessary to ensure high quality research projects continue to be developed.

An example of positive collaboration in research is the Chief Scientist Office ( CSO) work in partnership with rare diseases charities Action Duchenne and Muscular Dystrophy UK to co-fund a collaborative clinical research fellowship.

This project began when a grandfather of a child with Duchenne Muscular Dystrophy raised the issue of disparity in access to research with Scottish Ministers - patients were unable to access a number of important clinical trials in England. This led to a meeting with the CSO and the agreement to work collaboratively with Action Duchenne and Muscular Dystrophy. Importantly for the charities involved, this provided an opportunity to have a say in shaping the research fellowship. It was important to the charities that the post holder would have a clinical focus, and as such a fellowship which was 70% clinical and 30% research focus was agreed.

A further benefit for the charities involved was that, as grant holder, the CSO’s robust recruitment procedures were used and that the role was to be managed directly by the CSO. The project began approximately one year ago and the charities continue to be involved. Charities are in regular contact with the post holder and have the opportunity to contribute to the project’s development. The CSO also maintains contact with the charities, providing regular updates. This ensures transparency and ongoing patient involvement.

Dr Diana Ribeiro, CEO of Action Duchenne has said ‘This has been a ground breaking collaborative model - this should be used as a best practice example for translational genetic research for genetic conditions like Duchenne across the United Kingdom’.

5.3 Next Generation Sequencing ( NGS)

In addition, the Scottish Genetics Centres are now part of the SGP, who will develop the methodology for using Whole Genome Sequencing for diagnosis in Scotland. In the meantime Scottish laboratories continue to develop next generation sequencing for use as a diagnostic tool for genetics. Examples of developments include:

  • NHS Grampian’s development of BRCA1/2 NGS service has resulted in significant cost and staff time efficiencies, and consistently shorter reporting times. This service has been recently expanded to enable and provide BRCA1/2 somatic testing for eligible patients. Similarly, NGS application has also replaced existing Sanger services for the routine delivery of the national cardiac arrhythmias and familial hypercholesterolaemia services. NGS has also been used in the delivery of a newly commissioned service for Primary Immune Deficiencies ( PID)
  • NHS Tayside has implemented NGS into their diagnostic service for familial aortic aneurysms and phaeochromocytoma/paraganglioma. This is based on targeted amplification and sequencing of the genes most commonly associated with these conditions; currently there are 10 genes in each panel. In addition the laboratory is working with clinical colleagues to design similar panels for inherited diabetes, genetic skin disease, cystic renal disorders and Parkinson’s disease. These panels will offer a better service to patients and improve the laboratory workflow.
  • NHS Glasgow Laboratory is delivering Next Generation Sequencing for infantile onset epilepsy ( ION). In addition they have evaluated an extended Next Generation Sequencing panel for Disorders of Sexual Development ( DSD) which will shortly be available for routine diagnostic service delivery.
  • The NHS Lothian laboratory has issued over 2000 NGS reports in the past four years for disease specific panels for Stargardts disease, genes in the RASMAPK pathway, the hypertrophic and dilated cardiomyopathies, Hereditary Haemorrhagic telangiectasia, Alport syndrome, ocular malformations, primary microcephaly, cancer, neurodegeneration. Shifting to NGS technology has increased throughput and decreased costs.

A wide range of Next Generation Sequencing ( NGS) tests are available through the Scottish Genetics Laboratory Consortium ( SGLC)

In relation to developing and rolling out NGS services as detailed above, the Consortium Genetics Laboratories have undertaken evaluation of the performance of numerous testing platforms. In reference to exome the consortia laboratories have also begun to undertake some evaluative analysis e.g. following the experience gained through NHS Lothian pilot study, to evaluate Whole Exome Sequencing ( WES) in relation to Developmental Delay Disorders ( DDD) a outline proposal for the implementation of an exome sequencing strategy for the diagnosis of developmental disorders has been drafted.

The review of Genetics laboratory services conducted throughout 2016 included a comparative assessment of workforce across the Scottish Genetics Laboratory and Molecular Pathology Consortium service. It was recognised that the provision and sustainability of the highly specialist genetics and molecular pathology services was challenging given the lead times for training of skilled staff; and that workforce planning was required on a “Once for Scotland” basis to ensure succession planning in the light of the current age profile of staff in Scotland. The Review Group recommended that the future model of service should ensure adequate training opportunities and succession planning. This work will be taken forward under the revised consortia governance structure.

Recognising the continued need to develop genetics services, the Edinburgh laboratory created a partnership with the Institute of Genetics and Molecular Medicine ( IGMM) to devise a strategy to compliment the NES pre-registration scientists training scheme (on which there is a yearly limited intake) for training clinical scientists. Two fixed term posts for translational science initiatives in diagnostic genetics were created using a vacant unfilled clinical scientist post and funding from the IGMM translational Medicine initiative to appoint two IGMM Clinical Translational post-doc posts. A three year training plan has been devised.

The Glasgow laboratory received funding for two research and development scientists to work within the NHS laboratory following the approval of a Joint Working Project, via the NHS GG&C/Pharmaceutical Industry Alliance Partnership Group. The posts are funded for three years as part of this joint working partner initiative between NHS GG&C and pharmaceutical industry partners for the development and evaluation of services (including NGS) for cancer diagnostics. The long term strategy of the initiative is to build infrastructure and resources for sustained future development and translation into routine genetic cancer services, and it was recognised that there were difficulties in freeing up development time. Since the recruitment of two scientists in 2015, they have been working on a programme to develop the delivery of NGS for cancer which has included the evaluation of secondary and tertiary analysis software for, cross training of scientists in basic bioinformatics, along with the training of technical staff in NGS laboratory work flows.

5.4 Co-funding of research

Within the Scottish Government, the Chief Scientist Office ( CSO) has responsibility for the funding of clinical research. They work with a number of charities and have awarded over £1 million to studies into rare diseases. They are as follows:


Total Funding

Project Title

Action Duchenne Muscular Dystrophy UK


Secondary Osteoporosis and Its Therapy in Duchenne Muscular Dystrophy – ScOT-DMD

Motor Neurone Disease Assoc MND Scotland


Population based genotype-phenotype correlation to stratify incident cases of patients with MND in Scotland from 2015-2017

Muscular Dystrophy UK


Structural CNS changes, neuropsychological impairment and sleep disturbance in myotonic dystrophy

PSP Association


Improving diagnostic and care pathways in progressive supranuclear palsy and corticobasal degeneration

Scottish Huntington’s Assoc RS MacDonald Trust


Towards improvement in care delivery in Huntington’s Disease

This addresses Commitment 46, 47 and 48 of the UK Strategy for Rare Diseases.

5.5 Motor Neurone Disease ( MND)

Explanation: What is Motor Neurone Disease?

The MND Association describe Motor Neurone Disease as “a group of diseases that affect the nerves (motor neurones) in the brain and spinal cord that tell your muscles what to do. With MND, messages from these nerves gradually stop reaching the muscles, leading them to weaken, stiffen and waste.” [47]

The Scottish Government announced on 22 February 2017 that they were setting up the Gordon Aikman Scholarship to honour the late campaigner, who lost his fight with MND on 3 February 2017. The £50,000 a year will support individuals and professionals to develop, implement and evaluate practical interventions to improve the quality of life of people affected by MND. The scholarship will be run in partnership with MND Scotland.

The scholarship scheme will accept applications from people working in healthcare and from those affected by MND and their carers whose experience and expertise is invaluable in helping to continually improve care.

The scholarship will support individuals and professionals to develop, implement and evaluate practical interventions to improve the quality of life of people affected by MND. This may be through travel to identify best practice and/or using improvement and research approaches to test the impact and suitability of those interventions. This could include non-medicine based interventions such as specialised physiotherapy techniques, or non-medicalised assisted breathing techniques.

Projects are expected to be completed in 12 months. Successful applicants will be expected to share their findings, learning and best practice with their peers and across Scotland.

MND and MS PhD programmes

The 2016 SNP manifesto contained the following commitment:

‘We will work to support research into – and treatment of patients with – neurological conditions. Funding will be made available for three research Ph.D.’s in Motor Neurone Disease and a further three in Multiple Sclerosis’

The Chief Scientist Office was tasked with the delivery of this commitment, and following a rigorous external peer review process, a decision was in taken in November 2016 to fund a bid led by the University of Edinburgh to host the above-mentioned PhD Programmes.

The Edinburgh-led bid represents strong multicentre effort that will combine MS and MND in an integrated Scotland wide approach. The participating Universities (Aberdeen, Dundee, Edinburgh, Glasgow, St Andrews) have committed to fund an additional 6 PhD’s, bringing the total available to 12. There are plans to recruit to 4 PhD positions per year, thereby building a cohort over the 5 year duration of the programme (each PhD having a duration of 3 years). Recruitment of the first round of PhD’s has been completed (109 applications were received and 9 candidates interviewed). There were 4 successful candidates, and 3 of the 4 projects are on MND.

The work undertaken for MND helps to contribute to meeting Commitment 47 of the UK Strategy for Rare Diseases.