Advances in rare disease diagnosis 28 Feb 2023
While a rare disease is defined as a condition that affects fewer than one in 2,000 people, there are an estimated 7,000 rare diseases globally. Though they are individually rare, collectively they are common, with one in 17 people in the UK affected by a rare condition at some point during their life. In addition, it can take around five years or more for a family to get an accurate diagnosis.
Rare diseases disproportionately affect children, who account for 75% of cases. Of these, 30% die before the age of five. At least 80% of rare diseases are genomic, and half of these are found in children.
These facts were an important consideration when establishing the UK’s 100,000 Genomes Project, which was launched in 2013. This ground-breaking initiative achieved its aim of sequencing 100,000 whole genomes from NHS patients and incorporating genomic medicine into NHS care by 2018.
A pilot study conducted by Genomics England and Queen Mary University of London, in partnership with the National Institute for Health Research (NIHR) BioResource, analysed the impact of whole genome sequencing (WGS) on rare, undiagnosed diseases. Between 2014 and 2016 it sequenced the genes of 4,660 people from 2,183 families who were among the first to take part in the 100,000 Genomes Project.
The results were published in the New England Journal of Medicine in November 2021 and found that WGS had led to a new diagnosis for 25% of the participants. Of these new diagnoses, Genomics England reported that ‘14% were found in regions of the genome that would be missed by other conventional methods, including other types of non-whole genomic tests’. Diagnosis meant that these patients could go on to receive more targeted care, such as further family screening, a change of diet, vitamins and/or minerals, or other therapies.
The success of the pilot also supported the case for WGS to be included in the NHS National genomic test directory for rare diseases in 2018.
In January 2021 the UK Rare Diseases Framework was published by the Government, listing the priorities for rare diseases over the following five years. Among those priorities, the document stated, ‘We will build upon recent advances in diagnostic technologies, most notably in genomics and data analysis, to help patients receive a final diagnosis faster and reduce the “diagnostic odyssey” faced by so many’. The four priorities were:
- helping patients get a final diagnosis faster
- increasing awareness among healthcare professionals
- better co-ordination of care
- improving access to specialist care, treatment and drugs.
In February 2022 the Government outlined the progress that had been made towards these goals in its England Rare Diseases Action Plan. Among its achievements was the fact that the NHS Genomic Medicine Service (GMS) carried out over 600,000 genomic tests during the previous year, many for rare diseases.
Professor Dame Sue Hill, Chief Scientific Officer for England, commented at the time that the GMS was key to helping more patients get the right treatment quicker. She added, “The NHS already tests for more than 360 rare and inherited signs of illness covering around 3,200 rare diseases and 203 cancers though our National Genomic Test Directory, and, despite the pandemic, has continued to secure new, innovative and life-changing medicines to help people with rare and genetic conditions, including one-shot gene therapies, transforming their lives.”
Regarding access to specialist care, treatment and drugs, the National Institute for Health and Care Excellence (NICE) announced changes to its health technology evaluation processes to allow for new and emerging technologies, and provide more equitable access for those with severe and rare diseases.
In March 2021, the Government published Saving and Improving Lives: The Future of UK Clinical Research Delivery, setting out its vision of bolstering a patient-centred, pro-innovation and digitally-enabled clinical research environment.
An additional £340 million was allocated to the Innovative Medicines Fund to provide early access to promising new medicines, including cutting-edge gene therapies, in July 2021.
A further development since the Action Plan was published, was Government funding of £105 million to support Genomics England to speed up diagnosis of rare genetic conditions in newborns, that was announced in December 2022.
This year’s Rare Disease Day is focusing on equity, as ‘people living with a rare disease are more likely to experience treatment inequality, misdiagnosis and isolation’. Therefore it is fitting that Genomics England has been allocated £22 million to lead a Diverse Data Strategy to sequence the genomes of up to 25,000 research participants of non-European ancestry. These people are currently under-represented in genomic research, so this work will improve understanding of DNA and its impact on health outcomes, helping to reduce health inequalities and level up patient outcomes across all communities.
Alongside the efforts outlined above, partnerships around the world are also pushing the case for speeding up rare disease diagnosis. In Europe, the Rare Disease Moonshot was launched in December 2022, with the aim of scaling up public-private partnerships to accelerate research and drug development in this field through a coalition of seven organisations.
Meanwhile, Illumina – one of the companies that worked with Genomics England on WGS – is partnering with Genetic Alliance on a $120 million global initiative (the iHope Genetic Health programme) to increase access to WGS for low- and middle-income communities.
While some rare diseases may never be diagnosed, WGS and the increasing will to support research and precision treatments, mean there is rising hope for those with rare diseases and their families.
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