Bench to bedside: arthritic inflammation and pain

Medical researcher John Hamilton isn’t one to trumpet his achievements – though he could certainly be forgiven for doing so.

His tale is one of extraordinary perseverance and determination, and his unrelenting dedication to elimination of arthritic disease and pain has characterised much of his professional, and adult, life.

“Many years ago I suggested a particular protein, namely GM-CSF, might be a pro-inflammatory mediator in conditions such as arthritis, which was a novel idea at the time,” recalls the Deputy Head of the Department of Medicine at the Royal Melbourne Hospital and Senior Principal Research Fellow at the National Health and Medical Research Council of Australia.

“Over the years with talented collaborators, my laboratory has developed and tested this hypothesis in various animal models – particularly in arthritis but also in multiple sclerosis and lung disease – and we have found that if you deplete this particular molecule, you can actually shut down the disease.”

Based largely on this evidence, pharmaceutical companies are now targeting this molecule and there are several clinical trials underway in rheumatoid arthritis, multiple sclerosis and asthma.

Data from the phase one and two rheumatoid arthritis trials are reporting rapid patient benefit and it was announced in June that the technology in a patent covering Professor Hamilton’s work, licensed to leading international biotechnology company MorphoSys, is set to be developed and commercialised by GlaxoSmithKline.

“These discoveries have the potential to impact significantly on biomedical science, clinical medicine and patient outcomes around the world,” Professor Hamilton says.

Arthritis is the major cause of disability and chronic pain in Australia, with 3.85 million Australians affected. Rheumatoid arthritis, afflicting around 1 per cent of the population, is a systemic inflammatory autoimmune condition. Much more prevalent is osteoarthritis, which can also cause debilitating pain, stiffness, inflammation and damage to cartilage and joints.

Professor Hamilton’s interest in arthritic inflammation was evoked early on in his career when he witnessed first-hand the crippling effects of arthritis. His sister-in-law had suffered from juvenile arthritis as a young person, and he credits this early encounter with arthritis with shaping his later research focus – a scenario that he says is not uncommon.

“It is often the case that people who pursue research that is related to a particular condition or disease are committed to that field because they have witnessed its impact first-hand,” he says. 

More recently, Professor Hamilton’s lab has demonstrated that depleting the GM-CSF molecule can abolish inflammatory and arthritic pain. This is a major finding, as one of the key challenges osteoarthritis presents to both researchers and clinicians lies in effective pain treatment.

“To contextualise pain and inflammation, three out of the four top selling drugs worldwide are drugs targeting a particular inflammatory cytokine,” Professor Hamilton says. “If we’re successful in what we’re trying to achieve, our work may therefore have a huge global impact on the quality of life of those living with arthritis and other inflammatory and autoimmune conditions.”

Professor Hamilton notes that in a changing political and economic landscape, research such as his can no longer rely on government funding, with ongoing support for his work also coming from industry and private donors.

“Philanthropic contributions to medical research can have a truly transformative impact – not just on universities and research carried out, but on society itself,” he says.

With strong local and international collaborative links, Professor Hamilton has been and continues to be an invited speaker and lecturer at many conferences, academic institutions and pharmaceutical companies. This year Professor Hamilton has been invited to speak at the European League against Rheumatism (EULAR) Annual Meeting in Madrid, the International Congress of Immunology in Milan and the World Congress on Inflammation in Natal, Brazil.

For his part, Professor Hamilton says he is motivated most by a desire to improve the lives of others.

“I conduct my line of research in the hope that it will benefit many patients worldwide with illnesses related to inflammation and its associated pain.” 

“And for the intellectual challenge, of course.”

www.mdhs.unimelb.edu.au