AusBiotech special: Proteomics and disease diagnosis

Until the mid-1990s the term 'proteomics' did not even exist, but a decade on and the power of proteomics is now being realised.

Sydney proteomics specialist Minomic is now gearing up to commercialise two diagnostic tests - one for prostate cancer and one for type 2 diabetes.

Dr Brad Walsh, founder and CEO of Minomic, has been at the forefront of the proteomics revolution in Australia, having studied the proteins involved in wheat allergies for his PhD at Macquarie University and in rheumatology and arthritis at St Vincent's Hospital Centre for Immunology.

In those days, the study of proteins was still in its infancy and the techniques that are now routine were unheard of. Walsh was tempted back to Macquarie by another pioneer in the Australian proteomics scene, Professor Keith Williams.

Coincidentally perhaps, in 1995 the Federal Government began handing out much needed cash through the Major National Research Facilities funding round. A team from Macquarie put in a bid and a new entity, the Australian Proteomics Analysis Facility (APAF), was born, with Walsh the operations manager.

With welcome assistance from the US company Bio-Rad, APAF, began to design and build instrumentation to enable the early proteomics researchers to do what they wanted to do, "things like an automated machine to go and cut spots out of 2D gels even, which was just a pipedream at the time," Walsh says.

By 2001, however, Walsh was ready to go out on his own, to properly develop the intellectual property inherent in these new techniques and research methods. Again, he had assistance from the private sector, this time for the USA giant Waters Corporation. Waters came forward with seed capital to kick off Minomic, at that time consisting of just three people and a few ideas.

A major part of Minomic's business is contract research, having worked closely with New Zealand's A2 Corporation, the brewer Carlton & United, CSL, the Australian Red Cross and the probiotics company Probiomics.

The big stuff for Walsh, however, is the potential of proteomics for diagnostic applications. First off the rank is a way to diagnose prostate cancer that overcomes the limitations of the current prostate specific antigen (PSA) test and the dreaded digital rectal exam.

Prostate cancer

Walsh says the prostate cancer project began when Minomic was contracted by CK Life Sciences of Hong Kong to use its proteomics expertise to look at how a particular anti-cancer compound affected cells and the proteins they produced.

"We also needed to look at it at the mouse model level of cancer," Walsh says. "So we went to work with one of the best recognised prostate cancer researchers in Australia, Professor Pam Russell at the Prince of Wales Hospital. Pam and I formed a working relationship - we had done some work together back at APAF - on this [project] but also began to look at other opportunities."

One of those opportunities was a monoclonal antibody discovered by Russell for a prostate cancer antigen. The colleagues then began work on developing a non-invasive test to detect prostate cancer in urine.

"There is already the PSA test which is also an antibody to a protein, but PSA is not a good diagnoser of prostate cancer," Walsh says. "It is a good prognostic test after diagnosis - you can monitor it with PSA. But PSA can go up due to any stimulation of the prostate, because it is a naturally occurring protein.

"The problem with that is that if you happened to have made love before you go to the doctor then your PSA is probably going to be up, if you have ridden a bike, if the doctor does the DRE before taking the PSA, then sometimes that can raise it too. So what we are looking for is a protein that is raised in prostate cancer rather than naturally occurring in healthy individuals. And because the PSA is raised for other reasons a lot of men end up getting a biopsy who don't need it."

While Walsh cannot yet discuss exactly what the protein is, as the team's diagnostic kit is currently in the validation and early commercialisation process, he expects to have a prototype test kit available next year. He will, however, discuss the development of the antibody and the kit at AusBiotech in October.

Type 2 diabetes

A little further along the commercialisation road is Minomic's plans for a diagnostic test for type 2 diabetes. Minomic has detected a number of protein biomarkers that are increased in type 2 diabetes and is currently assessing how many biomarkers it will need and at what levels they should be measured before commercialising the test.

"There is currently a test that is quite acceptable - the blood sugar/oral glucose tolerance test. But that is a three-step process that takes time and effort - you've got to fast, have blood taken, drink a big syrupy dose of glucose, and then two hours later you have your blood test again and it's all about how does your body do on that.

"The estimate is that 40 to 50 per cent of people don't know they've got diabetes until they are becoming more ill, showing symptoms of kidney, eye, heart or nerve damage."

Walsh hopes to have a prototype urine-based, self-administered test available in 2009. "It's all about multiplexing - measuring three or four things at once in the same test tube or microtitre plate. But you have to work out each individual one and get the measurement right before putting it together.

In the meantime, Minomic has an ARC Linkage grant enabling it to continue a project with the School of Optometry at the University of NSW and the Vision CRC, studying the potential of revealing the progression of retinopathy in diabetics by looking at their tear drops.

"If there is a perturbation due to retinopathy you should be able to see a protein marker or a peptide in the tears," Walsh says.

"The tear fluid has maybe 100 proteins in it and probably 50 to 100 peptides, so it's not incredibly complex. What we are looking for there is differences between three groups - people without diabetes, people who are diabetic but do not have damage, and those with retinopathy. We want to see if we can pick it up before it gets too late."