Focus on Cardiff

Published on 01 October 2009
Source: Arthritis Today

A ‘molecule to man’ approach is the exciting description given to Arthritis Research UK's new centre of excellence at Cardiff University, launched recently as a world leader in finding new engineering and biomechanical solutions to treating musculoskeletal disorders.

Simon Jones and Bronwen Evans

For its second, prestigious national centre of excellence, Arthritis Research UK has chosen Cardiff University as the site of its new biomechanics and bioengineering centre. The centre is being funded to the tune of £2.5 million over 5 years by Arthritis Research UK, with a further £7.5 million funding from the university itself, guaranteeing a whole decade of research support.

The centre will bring together leading experts in a variety of research fields, creating close collaboration between engineers, biomedical scientists, physiotherapists and clinicians such as orthopaedic surgeons and rheumatologists, which will lead to the rapid translation of research to patient benefit in the clinic.

A joint venture

Biomechanics and bioengineering help us understand how the body maintains healthy joint movement, how disease or injury affect this movement, and how damage can be prevented or repaired. Measuring and treating joint movement problems is already an area of expertise at Cardiff. The team holds an outstanding reputation for its research and clinical achievements and has pioneered internationally adopted imaging systems, diagnostic and therapeutic strategies, and surgical and repair techniques. The biomechanics and bioengineering centre will advance joint research by harnessing technologies and expertise across several research areas to ensure an integrated approach. Six university schools (Biosciences, Engineering, Medicine, Pharmacy, Dentistry, and Healthcare Studies) are driving this project forwards committing six new lectureships and 11 PhD studentships – the first time that such a distinct range of disciplines have joined forces to address the arthritis challenge. The centre’s activities will be organised into three research teams led by Dr Debbie Mason (biomechanics, inflammation and pain), Dr Cathy Holt (biomechanics, motion analysis and rehabilitation) and Dr Sam Evans (mechanical loading of tissue cells and materials).

The director of the new centre, Professor Vic Duance, explains: ‘Take osteoarthritis, for example, in the earlier stages, non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed, but 15 to 20 years later the patient may be at the stage of joint replacement. What about the period in between? We aim to fill this gap by carrying out research to find out how this disease develops, and find new and earlier treatments to slow its progression and ultimately, halt it altogether.’

Movement and molecules

Joints need to be physically worked to stay healthy but repetitive, prolonged or excessive abnormal strain on joints is linked to the development of joint disease. By measuring how the cells and molecules in the joint tissue respond to the different stresses and strains caused by age, disease, injury and exercise, the team aims to build up a comprehensive picture of what happens during normal function and when joints go wrong. Measurements of the molecules involved combined with joint movement, pain and inflammation studies will allow researchers and clinicians to understand joint degeneration better and assess patients much more thoroughly.

“Investigating molecular mechanisms that cause joint degradation underlie our ‘molecule to man’ approach,” says Professor Duance.

Signalling molecules control disease

Signalling molecules pass biochemical signals between cells to ‘tell’ them what to do. In disease, parts of this communication network go wrong, and the research aim is to map out the molecular pathways and manipulate any faulty parts of it so that the correct signals are sent and received and cells can function healthily.

Daniella Riccardi Debbie Mason and Anwen WilliamsDr Debbie Mason, and Dr Daniela Riccardi, from the School of Biosciences, and Professor Simon Jones, Dr Bronwen Evans and Dr Anwen Williams from the School of Medicine are studying how mechanical force activates specific signalling molecules that influence joint health, but are also important in the control of pain and inflammation. “Some of these signalling molecules are present in rheumatoid arthritis and osteoarthritis joints at very high levels – 50 times higher than healthy joints,” says Dr Mason. “The latest imaging techniques can assess concentrations of these molecules in patients, and we’ve already found that these molecules cause the release of inflammatory chemicals in the joint. If we can find out how the system goes wrong in disease, we may be able to develop therapies to reduce pain and inflammation as well as prevent joint destruction.”

Imaging pain and movement

Pain is the major burden for patients with arthritis and understanding how it relates to joint function and degeneration is important for clinical assessment. “Patient scoring of pain is subjective and often very variable,” says Professor Duance, “and we need to have a better system of measuring it.”

Dr Sam Evans and Dr Cathy Holt, from the School of Engineering, explain how links between pain and joint function will be assessed with Dr Richard Wise, Director of fMRI, Cardiff University Brain Research Imaging Centre: “Functional MRI scanning allows us to see pain centre activity in the patient’s brain,” says Dr Holt. “We can place motion cameras in the MRI suite and measure knee joint movement and pain perception at the same time. We can then develop improved patient assessments that will help us to tailor treatment and monitor follow-up. Post-operatively, it’s common for there to be a lack of agreement between patient pain reporting and joint function. Pain relief is seen as the desirable outcome but functionality – the ability to carry out everyday tasks – is the key aim and we need to be sure that this is achieved.”

These studies will provide a better understanding of how joint function and pain interact, which could enhance surgical and physiotherapy treatments.

New physiotherapy parameters

Physiotherapy is one discipline where studies have tended to be carried out in isolation, therefore research will benefit from the input of the other research disciplines in the centre. Dr Robert van Duersen, Director of Physiotherapy and Dr Valerie Sparkes, lecturer, aim to study patients with knee injuries including anterior cruciate ligament rupture and those with non specific low back pain by combining physical functional and biomechanical measures, patient reported symptoms and biomarkers to get more detailed information regarding their conditions. “We’ll be looking at these conditions in more detail, much earlier in their development, and then tracking outcomes. We want to find out why some patients improve and others don’t and this will allow us to develop prognostic measures to help guide therapy more effectively and improve clinical outcomes.”

Dr Valerie Sparkes, Dr Sam Evans and Professor Vic Duance

Biomarkers to track disease

Biomarkers are produced by the arthritic joint as structural and functional damage develops. Healthy individuals only produce these molecules at very low levels or not at all, but in joint disease they are produced at increased levels that can be measured in blood samples. Tests to measure the levels of these molecules can then be developed to diagnose disease, monitor its progression and assess recovery after surgery or physiotherapy. This would be particularly useful in osteoarthritis for which there are currently no tests available.

Daniel Aeschlimann, Professor of Biological Sciences, School of Dentistry, explains: “We’ve analysed osteoarthritis and rheumatoid arthritis joint tissue and already identified several candidate marker molecules that look promising for clinical use. Once the tests are developed, we’ll use them to confirm that disease is present, and monitor disease progression and response to therapy. They could also be useful for predicting disease – could we screen populations and identify molecular changes that develop before active degradation of joints? This exciting approach could allow patients to be treated earlier during disease development before irreversible joint damage occurs.”

Toughening up implants

Although the centre’s focus is to devise strategies to delay the requirement for joint replacement, artificial hips and knees have transformed the lives of millions of sufferers and the centre also aims to improve the lifespan and quality of existing prostheses. Combined engineering (Dr Sam Evans) and pharmaceutical (Professor Stephen Denyer) expertise is finding ways of improving implant materials. Traditionally, cement is made of a plastic compound that is prone to cracking and brittleness. New ways of toughening it, such as the addition of rubber particles, and the introduction of novel medical polymers will provide the strength and resilience needed for superior implant materials.

Drugs that stimulate bone growth and reduce infection can be linked to the implant surface ready for release after surgery. This exciting development could lead to bioresponsive systems where surface coatings respond to infection or damage, releasing the appropriate drugs and repairing fractures in a self-healing way.

Patient involvement

None of this research would be possible without the input of patients, and over the time frame of the centre, the team aim to recruit several hundred patients into a number of co-ordinated clinical studies. This will contribute to a large database defining joint function in various disease states in the knee, hip, ankle, shoulder, elbow, wrist and the spine.

One major study will focus on patients who have undergone knee replacement surgery, and high tibial osteotomy (a surgical procedure used to delay the need for knee replacement in which the shin bone is re-aligned below the knee to reduce pain in younger people with osteoarthritis whose legs have become bowed).

Thirty patients and thirty healthy volunteers will be recruited over 5 years, and engineers will measure changes in joint function before surgery, and t3 and 12 months after surgery. Blood and synovial fluid samples will also be collected when joint function is being assessed, providing a unique snapshot into disease activity, joint function and pain perception at any given time.

“Our centre status will also enable us to widen our patient base to include a broad range of conditions such as osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitisosteoporosis and chronic spinal pain” says Dr Anwen Williams, from the School of Medicine. “In addition surgical patients with anterior cruciate ligament deficiency and reconstruction, rotator cuff, meniscal tears, sub-acromial impingement of the shoulder and spinal dysfunction will be assessed.”

Patients will be recruited during clinic visits. Recruitment will be made easier by the team’s support from clinical colleagues across Wales; the Wales Arthritis Research Network – a network of rheumatologists across Wales and orthopaedic surgeons and physiotherapists at the University Hospital of Wales and the Llandough, Royal Glamorgan and Royal Gwent Hospitals, together serving a population of more than a million people.

Chris Wilson, consultant trauma and orthopaedic surgeon at University Hospital of Wales, Cardiff and Rhian Goodfellow, consultant rheumatologist at the Royal Glamorgan Hospital, are directly involved in the research and management of the centre. “Arthritis and joint conditions are very common and affect most members of the population – from a young footballer with a bad knee injury to an elderly person with degenerative joints – and everything in between,” said Dr Goodfellow. “In clinic, it’s hard to tell patients that there’s nothing I can give them to modify their condition, and that I can only help them to help themselves. The opening of the centre offers those people some much-needed hope.”

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