Case study: Researching in rare diseases

Alongside running a busy clinic at the Royal Free Metabolic Kidney Stone Service, he is an Honorary Senior Lecturer in renal medicine at UCL and chair of the national Rare Disease Groups for hyperoxaluria and APRT deficiency. He has also served as the nephrologist member of the NICE Guidelines Committee for kidney stones and at the Quality Standards Advisory Committee.

As principal investigator and chief investigator for a number of interventional trials, he has an avid interest in rare renal diseases as part of the RADAR (National Renal Rare Disease Registry) network. In an initiative led by Dr Moochhala, the Royal Free has also recently become the lead centre for a new Rare Disease Collaborative Network (RDCN) in hyperoxaluria. 

Hyperoxaluria occurs when there is too much oxalate in the urine. Oxalate is a chemical which occurs naturally in the body but primary hyperoxaluria, a rare inherited condition, produces very large amounts that crystallise out in the kidneys causing recurrent kidney stones and worsening kidney function.

As the world prepares to mark International Rare Diseases Day on 28 February, raising awareness for those affected by rare diseases, we asked Dr Moochhala to tell us about his work in hyperoxaluria and what inspired him to contribute through research.

What first attracted you to research?

“I’ve always been interested in how the human body works at a detailed level, and I studied for an extra degree in pharmacology when I was a medical student. The project that I undertook was great grounding for research, and since then I’ve tried to always combine some form of research with my clinical medicine career.”

Why did you choose to embark on research in rare diseases such as hyperoxaluria?

“I spent four years researching kidney physiology during my PhD when I was in Newcastle upon Tyne. It was all about how molecules in the body are transported across cell membranes. During that time, I learnt about how kidney stones are formed. I discovered that we actually know more about the mechanisms of rare kidney stone diseases such as hyperoxaluria, than we do about some more common diseases.”

How does hyperoxaluria affect people’s lives?

“The hyperoxalurias are genetic diseases but can start causing problems at any age. Some children are severely affected from an early age, resulting in kidney failure needing dialysis and a dual (kidney and liver) transplant. Most patients have many episodes of kidney stones throughout their lives, which are unpredictable, painful and often need surgery. “

Which studies are you involved in at the moment?

“I am part of a team of committed renal researchers, and all the specialist centres have tremendous expertise in hyperoxaluria research. At the moment, I am Chief Investigator or Principal Investigator for eight studies in the field of hyperoxaluria. These include trials of a completely new class of drugs, called siRNA drugs, which have been specifically designed to target the abnormality in hyperoxaluria conditions.”

What do you love about working in research?

“It is very satisfying to be able to offer opportunities to patients to enable them to be at the forefront of new treatments. We have not had many breakthroughs in therapies for rare kidney stone diseases for many years, so to be able to be part of that is very exciting. The new class of siRNA drugs that we are testing have shown excellent results so far and we are keen to bring these into routine use for our patients as soon as all the trials have completed. The new hyperoxaluria network (RDCN) will bring together researchers nationally to help in this process.”

Why is research into rare diseases such as Hyperoxaluria so important? 

“Together, rare diseases affect about 5% of the UK population. But each disease is important and affects not just the patients but their families as well. Research into each rare disease is essential to work out how they affect people, and what treatments can be used. In the case of hyperoxaluria, research has resulted in some new drug discoveries that will hopefully be available in the NHS soon. This couldn’t have happened without scientists, doctors and patients working together in research.”

What is the RDCN and why did you want to get involved?

“The Rare Disease Collaborative Network is a new initiative by the NHS to group together hospitals and clinicians who are experts in a particular disease, focusing on research and improving outcomes for patients. It is a bit like the existing Highly Specialised Services but unfortunately does not come with the NHS funding of those services. But it is a good step forward for the hyperoxaluria community as it means that the NHS and the public can become more aware of the condition, and we hope that it will help in making new diagnoses and providing treatments. At least four new treatments for hyperoxaluria are already in clinical trials at RDCN centres.” 

How do you feel about leading the new centre?

“I feel very proud to help set up the new network. It is a privilege for me to work with my clinical colleagues across the UK who have huge amounts of experience, with our clinical trials teams at all the hospitals, and with the support of our patients and their organisations. It is national recognition that together our units have what it takes to become a world-class centre of excellence in hyperoxaluria.”

What are your hopes for rare disease and hyperoxaluria research in the future?

“I feel really excited for our patients and my colleagues around the country with an interest in hyperoxaluria. The community of kidney doctors and scientists in the UK already has a strong track record in rare diseases, and the hope is that this new network will build on those successes. We are at a crucial stage in terms of patient treatment, with new drugs available soon which look likely to revolutionise treatment of these serious disorders.”

What would you say to patients who are thinking of getting involved in rare disease research as participants?

“Being a research participant, especially in rare diseases, is one of the best things you can do for other people, and it may also help you directly. It helps other people become aware of the disease that you have to live with every day. New treatments can’t be found without our volunteers and we are hugely grateful to them. We try to make participation as easy and as much fun as possible, and most of our volunteers come back for more!”

What would you say to other healthcare professionals thinking of taking the first or next step in their research career?

“I would encourage them enormously. We are used to looking after patients in our clinical roles, but it is a great feeling to be able to make a contribution to science and use that to improve the care and treatment we give. This can only be done via research. There are so many opportunities that there is sure to be something valuable and exciting for everyone!”

To find out more about pursuing a career in NIHR research visit: Your Path in Research