Kidney Research UK has announced a £2.55m ($3.42m USD) investment from the Stoneygate Trust to fuel research aimed at researching and developing treatments for Alport syndrome. The condition is a rare genetic disorder but the second most common cause of inherited chronic kidney disease.
The hub (based at the Wellcome Trust Centre for Cell-Matrix Research in Manchester) will be headed by Rachel Lennon from the University of Manchester, in collaboration with Daniel Gale from University College London and Neil Turner from the University of Edinburgh. The research team reportedly hopes the hub will serve as a model to address a range of kidney diseases and conditions in the future.
Outsourcing-Pharma connected with Aisling McMahon (executive director of research, innovation, and policy with Kidney Research UK) about the hub.
OSP: Could you please tell us a wee bit about Kidney Research UK—who you are, what you do, any recent achievements you’d like to brag about, etc.?
AM: As the UK’s largest kidney research charity, our goal is to fund vital studies into new and groundbreaking treatments for kidney disease. Once someone becomes a kidney patient, they have to live with the condition for life as there is still no cure for this chronic disease.
As part of our mission to transform treatments for kidney patients, we are investigating new and exciting treatment options including advances in gene therapy, medical innovations, and utilizing the latest findings on how patients can improve their quality of life through diet and exercise.
Our funding into research has extended into a number of fields looking into the impact of COVID-19 in kidney patients, improving outcomes for dialysis patients, and of course funding research into rare conditions such as Alport syndrome.
In recent years we have looked beyond the laboratory to raise awareness and participation in organ donation and in medical research with marginalized communities for whom these topics can be taboo.
OSP: Please tell us about Alport syndrome, and why this particular condition is especially worth pursuing treatments for.
AM: Alport syndrome is the second most common inherited kidney disorder after polycystic kidney disease, and it also causes hearing loss and eye problems. It is caused by faults in one of the type IV collagen genes that create the normal glomerular basement membrane. This scaffold of proteins is at the core of the filter mechanism in the kidney.
At its most severe, when there is no normal Alport gene, the condition has long been known to cause kidney failure and deafness in teenagers and young adults. Family members with one faulty and one normal copy of the gene are also at increased risk of serious kidney disease. However, faulty Alport genes are now also being identified in unexpected conditions and seem to play a wider role in other types of kidney disease than was previously thought.
When Alport syndrome causes kidney disease it leads to kidney failure and it shares many features with other conditions that affect kidneys. By pursuing a greater understanding of Alport syndrome, we have the opportunity to learn more about kidney disease in general and to progress treatments that are based on a deep understanding of how kidneys are affected by disease processes.
Alport syndrome is also caused by a fault in one of three genes, making it a promising candidate for gene therapy.
OSP: Can you share a little bit more about the Alport Research Hub, including the scientific talent who’ll be contributing work, what its base at the Wellcome Trust Center entails, and any short- or long-term goals you might have?
AM: Our vision for the Alport Research Hub is to bring together a network of UK researchers to progress the investigation of new treatments and to study the genetics of a large group of individuals with Alport syndrome.
The new treatments will be tested in research laboratories based in the Wellcome Centre for Cell-Matrix Research, in Manchester where there is expertise in the study of protein scaffolds known as basement membranes. For the detailed study of genetics in individuals with Alport syndrome, the physical hub in Manchester will link to a virtual hub with experts in London and Edinburgh and together researchers will analyze whole genome sequencing data from patients with Alport syndrome.
The hub will be directed by Professor Rachel Lennon (University of Manchester) in collaboration with Professor Daniel Gale (University College London) and Professor Neil Turner (University of Edinburgh), all hugely accomplished leaders in the field.
There will also be a restricted fund for an open call for three new project grants to encourage innovative ideas and potentially nurture new researchers in their academic careers in the kidney field.
Some goals of the hub:
Finding biomarkers to detect levels of kidney damage. The team will test for biomarkers in the urine which will assess the stage of kidney disease and help to guide clinical decisions.
Identifying and testing new treatments. Some new treatments are coming along that may slow many diseases where there is a protein leak from the kidneys, as in Alport syndrome. Large-scale clinical trials in patients are needed to find this out but to justify the expense and risk of conducting trials there is a significant need to first test potential new therapies in the laboratory using cells, organoids, and animal models with features of Alport syndrome. Establishing and maintaining a testing platform would therefore substantially improve evaluation of potential novel treatments created by academic and industrial research teams and, in addition, would help with basic research to understand the mechanisms by which faults in the gene can lead to kidney damage and other problems.
Identifying the patients who could benefit most from new treatments. The UK’s RaDaR (rare kidney disease registry) has over 850 patients with abnormal Alport genes and there are opportunities to add more patients to the registry. Some of those most likely to benefit from new treatments have the most severe changes in Alport genes, making them most likely to deteriorate early and, given the rarity of the condition, limiting their opportunities to participate in clinical trials. Studying a large and detailed data source such as RaDaR offers the possibility of identifying these genetic or environmental disease modifiers.
Testing whether gene therapy can work in Alport syndrome. This exciting treatment option could lead to a cure for Alport syndrome, even in patients with the most severe gene defects. However, there are many hurdles to overcome with the delivery of the correct gene to the right cells in the kidney and this will require careful and focused research. This research can be accelerated if several academic and industry teams collaborate.
OSP: You mention there’s been diagnosis and treatment progress in recent years, but more is needed. Could you please elaborate on that?
AM: The considerable advances in genetic technologies over the past decade have improved the availability of genetic testing for Alport syndrome and this is now the first-line investigation in the UK for making a diagnosis. In addition, over the past five years, there has been a huge increase in developing new treatments for Alport syndrome and there are now several new therapies in clinical trials. Whilst there are still no treatments that have been formally approved specifically for Alport syndrome, this may not be too far away.