The next stop on the tour of aHUS expert centres was in the UK at the University of Newcastle upon Tyne Hospital. The hospital has had an interest in familial HUS, or aHUS, for decades and it was here that the first ever disease predisposing Complement mutation ( in CFH ) was discovered by the Warwicker/Goodship group in 1998. It is now the location for the National Renal Complement Therapeutics Centre (NRCTC).
Led by Professor David Kavanagh the NRCTC has been established by the National Health Service as the specialised service provider for aHUS in England. (Scotland, Ireland and Wales having their own NHSs) The recommendation by NICE who had evaluated eculizumab was an expert centre ( its wording) should be part of the delivery of eculizumab for the treatment of aHUS in England. Newcastle had applied and were selected to be this centre.
But the NRCTC scope is much more than just being the pre-scribers of eculizumab and it contains three core elements. As well as the aHUS Service, it does the same for MPGN, and also has a dedicated Complement Therapeutics Research Group.
Alliance delegate arriving at RVI.
With a staff of over twenty working full or part time across the Hospital and University campuses the NRCTC comes together in its own location in an old ( 19th Century) part of the Royal Victoria Infirmary, and it is there that the alliance went to be greeted by some of the doctors , nurses and administrative staff of the Centre.
After introductions and a chance to meet Doctors Sally Johnson, Edwin Wong , Michal Malina (right to left), Nurses Johanne Stout, Angela Watts and Manager Jalibani Ndebele (left to right), Professor Kavanagh outlined the work of the Centre . He preceded his talk with a video that had been produced about the NRCTC and aHUS. The expert centre has a wide scope of activity including Clinical care, Diagnostics, Genetic testing, Genetic counselling, Treatment ,Clinical trials and Patient stratification.
In a shared care approach with local renal units throughout England , the Centre is the provider of the initial genetic screening of patients suspected of having a TMA which may be aHUS related. There is an established protocol for gathering relevant data ahead of testing to decide whether it would be appropriate to prescribe eculizumab. David explained how from a confusing mass of TMA possibilities the Centre had to determine what to do from the data gathered. This is not left to one doctor and through team discussion and a democratic decision process a decision is made by the doctors. Each year about 20 to 30 aHUS patients are identified by this process and are prescribed eculizumab, as well as those being referred for transplant.
Under a standard protocol the genetic testing of referrals is provided by the hospital’s DNA Genetic Centre, and Sanger Sequencing is done of the standard panel of known Complement mutations, including for C5 SNPs , which prevents eculizumab from working. The Centre also offers genetic screening for international referrals alongside its UK commitments.
In a shared care approach aHUS patients in England have the opportunity to visit the National Centre ,or to meet with its specialists over the internet in a secure tele-consultancy. It can take over an hour per patient to put together a care plan to discuss. The Centre is focused on building relationships with patient and outreaches to them, either one to one as the Centre’s nurses do to answer individual specific concerns, or, via occasional patient meetings in different parts of the UK. A regular newsletter about the Centre is sent out to maintain engagement with aHUS patients and families. There are plans to do more on information for patients, such as a “school advice” leaflet.
Specialist Nurse Angela Watts shows the alliance a poster of the research done on patient information needs.
There is also a website run by the National Renal Complement Therapeutics Centre (NRCTC) with information and advice designed for patients as well as clinicians, and the latter are also visited in an ongoing programme. Their National aHUS Service offers a robust array of news, services and events, as well as a traveling aHUS Roadshow that brings information directly to patients and their families. The Centre also has set up a patient steering group of patients from the UK to provide feedback on its services.
Visiting the research laboratory in the University, the alliance had the chance to find out from Dr Kevin Marchbank and Professor Claire Harris about the research work going at the Complement Therapeutics Centre. Essentially they are looking at the fine detail of Complement mutations ( and Anti Factor H Autoantibodies) to understand the mechanisms by which the defects found are causing the disease to manifest. As an example, they explained that the problem in the first Complement mutation found in CFH was the switch of the normal “Argenine” part of the gene to “ Glycine” altered the ability of that CFH to attach its self to another part of Complement to control it ,because it had simply “lost its magnetism” as Argenine is highly charged ( polarised ) and Glycine isn’t. For every mutation there is different impact and the Centre’s researchers are finding out what that is and then try to develop a therapeutic product to counteract its effect. This takes up a lot of Clare’s time, but it is something she is familiar with having also worked in the pharmaceutical industry .
The alliance also discovered from Kevin that a unique facet of the centre is its affiliated mouse model programme which he has developed with colleagues. Over 10 years in the making, an animal model with aHUS knock out genes has a potential to make a positive impact on not only our knowledge base of aHUS mutations but also for testing new drugs regarding clinical trials of effective therapeutics.
Much discussion then surrounded the issue of the monitoring need and the monitoring methods needed for those patients in remission, or even those predisposed with no aHUS onset , including what is a normal baseline for them.
Clare, who is a leader in the International Society of Complement, and Kevin, along with the others in the Centre have collaborated on research internationally and spoken at national and international conferences and events , thereby ticking many of the boxes of what constitutes an aHUS expert centre.
The alliance was appreciative of the time the Centre’s staff gave to the visit as it was a working day for them with clinics and even emergency events. It built on our knowledge of , and the identification of emerging issues, in our pursuit of an understanding of expert centres.
For a long time the Newcastle group has been working to improve understanding and treatment of aHUS for the benefit for both the local and international aHUS community, and the aHUS alliance is very appreciative that it does so.
Whistle-Stop Tour of 4 aHUS Centers in the EU: Visits to Three Nations in 6 days
1st Stop: Paris FRANCE
2nd Stop: Newcastle upon Tyne ENGLAND (UK)
3rd Stop: Bergamo ITALY
4th Stop: Milan ITALY