Alexion and BioMarin, both members of Genomics England’s Discovery Forum, have identified previously undiagnosed patients with life-threatening kidney and neurological diseases.
Diagnosing children likely to develop kidney failure
Nephronophthisis (NPHP) is a childhood genetic disorder primarily affecting the kidneys. It is rare (around 1 in 60,000 births) and usually results in kidney failure by the age of 15. It is responsible for 15% of cases of childhood end-stage renal failure – with no preventative treatments currently available.
Using Genomics England’s dataset, global biopharmaceutical company, Alexion, has identified 14 undiagnosed patients, recruited as part of the 100,000 Genomes Project’s rare disease programme, who carry the gene deletion causing the disease. These findings have been shared with Genomics England and fed back to the patients’ NHS clinical teams.
NPHP is a severe and devastating disease with significant unmet medical need. Our work with Genomics England has enabled us to identify previously undiagnosed NPHP patients, and it has helped us to understand the wide clinical spectrum that these patients show.
Dr Guillermo Del Angel
Senior Director, Data Science, Genomics, and Bioinformatics at Alexion
This discovery is an exciting first step in a broader collaboration between Alexion and Genomics England in applying data sciences and artificial intelligence across a spectrum of genomic and clinical data. The aim is to accelerate the diagnosis of patients suffering from rare diseases, enable paths of intervention, and bring hope to those with the disease and their families.
New hope for Batten Disease
Neuronal ceroid lipofuscinoses 2 (CLN2) is a very rare, inherited disorder caused by mutations in the TPP1 gene, and is one of a group of life-limiting conditions collectively known as Batten Disease. The symptoms typically emerge in children between the ages of two and four. CLN2 can lead to seizures, muscle twitches, vision loss, intellectual disability, and behavioural problems. Around 30-50 children live with the condition in the UK, and life expectancy is around 10 years. Currently, there is no cure or life-extending treatment for CLN2.
Biopharmaceutical company BioMarin, is another Discovery Forum member focused on rare disease patients. It has identified one patient recruited into the 100,000 Genomes Project for a condition unrelated to CLN2, but who carries two pathogenic mutations of the TPP1 gene. This new information has also been fed back to the patient’s NHS clinical team.
BioMarin intends to engage the UK’s National Institute for Health and Care Excellence (NICE) and NHS England on the use of its cerliponase alfa treatment for patients with CLN2 in England. Ultimately, it is hoped that the work from BioMarin and others, supported by evidence from the Genomics England database, will bring clinicians more treatment options for patients with CLN2.
The focus of rare undiagnosed diseases in Genomics England’s 100,000 Genomes Project provides us with a unique opportunity to better understand the clinical spectrum of devastating childhood diseases, and to develop targeted therapeutics that can impact patients and their families. We are excited about these initial findings and about improving alignment between disease diagnosis and access to available therapeutics in the UK and around the world.
Dr Lon Cardon
Chief Scientific Officer at BioMarin
These two examples highlight the range of value that Genomics England’s Discovery Forum is providing to multiple stakeholders. Access to the data is allowing drug developers to strengthen the body of clinical insights for target cohorts; in turn their work is immediately fed back into clinical reporting that Genomics England provides for Project participants through the NHS.
This work exemplifies the Discovery Forum aim to improve patient outcomes. It is a goal that relies on a variety of stakeholders working together and sharing knowledge. While the dataset is a valuable research asset, it is the researchers themselves who will define its value.
The 100,000 Genomes Project has succeeded in its role as a pilot project for establishing a genomic medicine service through the NHS. Our ambition is to grow the legacy of the Project to improve patient outcomes across the globe. Through the Project, and in collaboration with our clinical delivery partners across the NHS, we have built an extraordinarily rich dataset that will continue to grow in breadth and depth.
The potential applications of this are exciting. There are clear immediate benefits in developing new diagnostics technologies and data analysis tools. There are also long-term benefits that tie in with the paradigm shifts we are seeing in the pharmaceutical industry. We are leaving the age of the block-buster drug. The focus has moved to targeted therapies, drug repositioning, and reducing the failure rate of clinical trials. It is here that we see a lot of exciting potential applications of the 100,000 Genomics Project cohort data.
Chief Commercial Officer at Genomics England
People signed up for the 100,000 Genomes Project in the hope that their data could be useful in advancing scientific discovery as well as, perhaps, helping them individually. This news demonstrates that the Project is starting to make tangible progress on both of these fronts.”
Chair of the Genomics England Participant Panel