Diagnostics
Proteomics has only been around since the 1990s, but is billed by some as the future of personalised medicine. This is because proteins can provide exceptionally granular and specific information about what’s happening inside the body. To provide an analogy, our genes provide instructions for how the body should function, while proteins are the workers that carry them out. The problem is that they don’t always do so as planned. Protein activity can change with alterations in the body’s environment, such as with age or as diseases start to develop. Put another way: genes can indicate what the body might do, but proteins can tell us what it’s doing right now. By studying proteins, we can gain novel insight into the biological changes that precede disease and happen as it worsens. Not only could this help us discover health problems sooner, but it opens new avenues for drug development and therapy options.
Predicting disease
Because our makeup of proteins can shift as the body enters or approaches a disease state, being able to spot these changes means we can predict illness at an earlier stage. “With pancreatic cancer, when most people go to the doctor with stomach pain it’s too late, it’s stage four,” says Dr Christoph Borchers, professor of oncology at McGill University and director at Segal Cancer Proteomics Centre. But if we had a routine blood test that could identify a protein that’s a predictive marker for pancreatic cancer, preventative action could be taken. Borchers explains that by looking at someone’s entire set of proteins – known as their proteome – we can look for associations with all kinds of diseases. “This is where we are going,” he adds. “We’re not there today, but it will come very soon.”
Thanks to advances in technology, we can now identify more proteins than ever, but there’s still a way to go. There are thought to be over 20,000 proteins within the human body, but if you got a blood test in the clinic today, it would probably show 30 at most, says Ferrucci. However, in the lab, tools such as liquid chromatography mass spectrometry can identify upwards of 1,000 proteins, while newer technology, like the SomaScan platform from SomaLogic can spot 7,000 from a 55-µL sample. But as well as identifying a protein, we need to be sure about what it does before making any clinical decisions, says Ferrucci. “There’s a lot of research that’s been done on a large scale – but not as large as I would like to see – to understand the diagnostic power of these proteins.” Eventually, he adds, the aim is to group proteins into profiles that are either associated with, or predictive of, disease.
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www.practical-patient-care.com New drug targets
“When we are looking at diseases, we’re not looking at one protein. We’re not even looking at several proteins, we’re looking at pathways now,” says Borchers. Proteins carry out vital jobs, including fighting infection and regulating essential mechanisms. When they behave in different ways this creates biological changes within the body – which can disrupt our functioning and lead to disease developing. If we can identify which proteins play important roles within these pathways, we can target them with drugs that inhibit their activity. “We can say, ‘Look, all of a sudden, this pathway is upregulated. It looks like this protein has a major role. If you knock it out, what happens?’,” Borchers explains.
Experts hope that proteomics will enable doctors to identify a wider range of health risks than they can with a typical blood panel.
“When we are looking at diseases, we’re not looking at one protein. We’re not even looking at several proteins, we’re looking at pathways now.” Dr Christoph Borchers
Analysing the shape of the protein, known as structural proteomics, can also give us an insight into how it behaves within a pathway. When a protein changes its shape, this alters its function. Take a neurodegenerative disease that’s brought on when particular proteins change their shape and clump together. If you knew how their structure changed to get to that point, you could create a drug that prevents those changes from happening – which could stop the disease from developing, says Borchers. This may be where we’re headed, but we first need to make sure we can determine which proteins are causally
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