Meet the Researcher: discovering the secrets of osteoarthritis with Professor Nidhi Sofat

Published: 07 March 2019

Professor Nidhi Sofat

Please describe your research interests and what you are currently working on?

I specialise in both rheumatoid arthritis and osteoarthritis. It’s been a fascinating time for this area of research, partly because of the astonishing leaps forward in rheumatoid arthritis. When I was a medical student we would see these patients in wheelchairs, needing joint replacements; but new drugs have transformed the outlook for this condition. The first so-called biologic DMARDS, or disease-modifying anti-rheumatic drugs, were groundbreaking but expensive; now there are lots of copies and alternatives.

Osteoarthritis is quite different in terms of the progress made. It’s the most common type of arthritis in the UK and is really the next frontier. This is where we at St George’s are busy with various trials. We have one trial that is looking at nerve growth factor inhibitors. Nerve growth factor is released when you hurt yourself, for example when you bang your finger. Studies are investigating whether Inhibition of this has a direct effect on the pain that osteoarthritis sufferers feel. The data is looking promising.

We’re also starting a trial with the Wellcome Trust and Rosetrees Trust that is looking at reducing pain in patients with osteoarthritis in their knees by measuring biomarkers in their blood, joint fluid and urine over the course of three months. We also measure their pain scores. If they have fluid on their knees we remove that and give them the option to inject steroids into the knee. After three months, we see if those markers have changed after the injections. We compare them to markers in patients with other types of arthritis, including rheumatoid and spondyloarthritis.

What sort of biomarkers are you are looking at?

In 2017 we published a paper in the Annals of Rheumatic Diseases (part of the BMJ group) that looked in close detail at the bone marrow lesions that are seen in osteoarthritis. When the bones change because of the condition, typically cysts start forming in the joints as the bone tissue erodes. We were the first to look inside the cysts at this tissue – believe it or not no-one had looked at this before! One of my PhD students Ana … found some really exciting changes including new cartilage and new blood vessels. This is already significant as nerves tend to travel with blood vessels so that could be a link to the pain being experienced there. But the really novel part was to look at the genes in this tissue. We found 218 genes and have identified them with the help of the gene bank.

The genes we found covered several pathways; some involving pain; some involving the breakdown of tissue, some involved in laying down new nerves. There are lots of processes going on at the same time. And these are the genes we will be looking out for in this new study and seeing if we find them in the patients’ samples as proteins.

What will the next step be now you’ve established the genes that are expressed in this condition?

We want to do more work on how the process of the lesions forming starts and develops, and I’ve applied for funding for that. We also want to do more work on how to distinguish regular knee and joint pain from arthritis-specific joint pain. This is something GPs often struggle with – it can be quite challenging to diagnose which is why time to referral can take time. If it was possible to find a way to identify the condition definitively with diagnostics, that would be a huge step forward and may lead to more personalized treatments.

How do you fit in your clinical practice at St George’s Hospital – and do the two link in?

Yes – I conduct clinics in general rheumatology, inflammatory arthritis, vasculitis and osteoarthritis at the Hotung Centre. I also care for patients on rheumatology specialist wards. My work is very much ‘bench to bedside’ – the research directly informs my care. My cases are often very complex with multiple conditions layered on top of the arthritis.

The rheumatologists in the hospital have been working closely with local GPs to alert them to the symptoms of rheumatoid arthritis. Since it was made the subject of a QIPP (Quality Innovation, Productivity and Prevention programme) a few years ago, we are keen to improve referral times to consultants from GPs. If patients are complaining about symptoms that involve aching, stiffness and feeling tired, those are general symptoms; but GPs can now get to work on screening the antibodies straight away and checking blood for inflammation. Then when there is a referral we have all the information we need. The treatment pathways for the appropriate medicines are NHS- and NICE- approved, so there is now a major incentive to diagnose the condition earlier as it makes such a difference to quality of life for the patients when they are prescribed those medicines.

What other interests do you have outside your work at St George’s?

I sit on the committee of the British Society for Rheumatology and am involved with Versus Arthritis. This charity was formerly known as Arthritis UK and is raising awareness of the fact that arthritis isn’t only a condition affecting the older generation; rheumatoid arthritis often presents in the late 20s and is much commoner in women. It’s known that auto-immune conditions affect women disproportionately, but the reasons for this are not fully understood.

My interests outside are St George’s are practising yoga, which I find very relaxing, keeping up with my two young boys and trying to grow interesting plants – last year I managed to get my rhododendron to flower after 3 years, which I was very proud of!

Lastly – today is International Women’s Day – has your gender ever been an issue for you?

Although scientific careers have traditionally been thought of as male-dominated, I was always interested in science right from my school days; particularly in how our immune systems deal with infections and also in how the body attacks itself during autoimmune disease. My desire to learn more about what interested me always inspired me to keep finding out more, which led me to do develop my research with a PhD and continue my clinical career in Rheumatology.

Once you have a family, it can be quite challenging to keep up with the demands of family and work, but by building a support network around me I have been able to work on what I really love, which is scientific discovery in the field of rheumatology and be a good mum and wife too. For me it's been essential to have friends and family around who understand what I do, and mentors for advice and support.