Patient-led research features in Rare Diseases Action Plan for England

To coincide with publication today – Rare Disease Day 2023 - of the second Rare Diseases Action Plan for England, we’re delighted to expand upon one of our case studies featured in the Department for Health and Social Care’s annual update on progress in their efforts to support the rare disease community.

Our Rare Diseases BioResource comprises patients and family members from 50-60 rare disease areas and is a unique resource for overcoming the challenges associated with conducting rare disease research, particularly the process of efficiently recruiting research participants.

Disparate groups of patients – and their genetic, phenotypic and health and lifestyle data, along with NHS records – are brought together into one central source of information for researchers to access.

The very nature of a rare disease means the diagnostic odyssey can be long and difficult for patients and their families. Once diagnosed, the prospect of improved patient outcomes or care is limited by the fact that many rare diseases are significantly underserved in terms of therapeutic discovery, in part due to the complex biology behind structural genetic variants that cause many rare diseases.

Undeniably there are also commercial pressures that mean rare disease research is often overlooked because of the perceived smaller population that stands to benefit, despite rare disease research often being fundamental to understanding more common diseases.

The UK government’s Rare Diseases Action Plan for England is a welcomed annual report on national efforts set out in the UK Rare Diseases Framework: to improve speed of diagnosis, raise awareness amongst healthcare professionals, improve coordination of care, and access to specialist interventions.

The diagnostic decline faced by patients and families of one ultra-rare form of epilepsy led to a unique partnership between the patient group Ring20 Research and Support UK CIO (Ring20) and Illumina - a global leader in DNA sequencing and array-based technologies – on a study called UNRAVEL: making genomic understanding in ring chromosome 20 syndrome possible.

Phase I of UNRAVEL launched in January 2021 and sought to raise awareness and build expertise within the community around the experience and science behind diagnosis and its methods.

Ring20 logo

Allison Watson, Ring20 CEO said:

“Ring chromosomes occur in 1 in 30,000 to 60,000 births so collectively not so rare. It is estimated that only 1% of ring chromosome cases are currently diagnosed.

“Ring20 are passionate about driving patient-led research to try to move the dial forwards in both diagnostic opportunity and therapeutic discovery to improve health outcomes. We are very proud to be partnering with industry, but we also work very closely with other patient organisations supporting those affected by ring chromosome disorders including Ring14 International and Unique – the rare chromosome disorder group.

“Additionally, we recently established UK Rare Epilepsies Together (UKRET), a network of UK based patient groups supporting those living with rare and complex epilepsies and their families to address common unmet needs at a national level”

Ring Chromosome 20 Syndrome, or r(20) syndrome, is a very rare condition in which one of the two copies of chromosome 20 has formed a ring rather than the typical linear chromosome structure.

The consequence of the ring formation is a difficult to control epilepsy, typically with onset in early childhood and associated with intellectual disability and behaviour problems which may be progressive.

It is believed to be underdiagnosed or misdiagnosed in some people with epilepsy.

To enable the scientific partnership to work on unravelling the genomes of r(20) patients to identify new cases and develop an effective diagnostic test for the future, Ring20 contacted the NIHR BioResource to propose a collaboration on a new patient cohort to facilitate research efforts into r(20) syndrome.

NIHR BioResource has been working with Ring20 to collect DNA samples from a subset of r(20) syndrome patients for Phase II of the UNRAVEL study.  Samples provided to the NIHR BioResource have been shared with Illumina in order to undergo whole genome sequencing (WGS).

The goal is to use WGS to detect the genetic variations that underlie ring chromosome 20 syndrome and to consequently further our understanding of ring chromosome syndromes. The hope is that this will support efforts to diagnose ring chromosome conditions and improve patient outcomes.

Dr Shirlene Badger, Head of Patient Advocacy, Illumina said:

“We are at a pivotal point where genomics is giving us greater insight on the variations that explain symptoms and enable diagnosis. However, we know that there is a long way to go to improve knowledge and access, especially for ultra-rare conditions such as r(20).

“While we can see the ring with cytogenetic methods, we do not yet know what causes that ring to form. This important research is about trying to increase the resolution of that view. At Illumina, we value the power of collaboration. The problem of diagnostic decline is one that cannot be ignored and it requires shared problem-solving, learning, and collaboration if we are going to unravel the genomics of r(20) and improve outcomes for rare disease families.”

A priority for 2023 is establishing a ring chromosome patient cohort within the Rare Diseases BioResource.

The NIHR BioResource is continuing to partner with Ring20 Research and Support UK CIO to assist with participant recruitment, sample collection, and providing the governance and ethics framework for establishing the patient cohort.

This model is currently used for more than 50 rare diseases at the NIHR BioResource and has been very successful with other charity partners such as the Cystic Fibrosis Trust.

The project is led by Principal Investigator Dr Fernando Pinto and a team from Royal Hospital for Children in Glasgow and supported by the Patient Led Research Hub (PLRH) in Cambridge.

Commenting on the collaboration and hopes for the future of r(20) and epilepsy research as a whole, Allison added:

“We are very grateful to the NIHR BioResource and Illumina for listening and responding to our challenge. Our hope is that the new ring chromosomes rare disease research cohort will be an enabler to fostering future research interest and collaborations. Now is an optimum time to invest in researching these underserved conditions, with the approval of the Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders (IGAP) and the results of Epilepsy Research UK’s UK Epilepsy PSP setting the priorities in epilepsy diagnosis, treatment and care over the next 10 years.

“It is imperative that ring chromosomes are not left behind and our needs are addressed within the UK’s Rare Diseases Action Plans. Success in r(20) syndrome can equal success in other epilepsies.

“There has never been a greater interest in r(20) syndrome. r(20) syndrome is ripe for research. The time for change is now. Carpe Diem.”

Collaboration – between government, NHS, academia, industry and the patient community – is fundamental to success of this framework. The NIHR BioResource is proud to work with our research partners to continue our support for vital rare disease research.

Find out more about the newly published second Rare Diseases Action Plan for England, which features two NIHR BioResource case studies on how our work is supporting rare disease research: this Ring20 project and our interview with a family taking part in our Rare Diseases RNA Phenotyping project.

Find out more about our Rare Diseases BioResource, including the conditions we are currently recruiting patients with, and the studies our volunteers have supported over the past 15 years.

If you are a researcher interested in finding out how the BioResource can facilitate your research by providing samples, data or participant recall, please get in touch today.

You can keep up to date with the NIHR BioResource on Twitter and LinkedIn. 


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