Why people with Parkinson's start to smell different

Professor Perdita Barran and her team at the University of Manchester have also been doing lots of interesting research on Parkinson's - including why people who have or are going to get the illness - to some people - start to smell different. Retired nurse Joy Milne, whose husband had Parkinson's, noticed this many years before his diagnosis, and she’s since been proved right. A "super smeller", she can pick up on people destined to develop the condition in the years ahead…

Joy - It can be a curse but it in this instance it's a superb gift I’ve been given. And I feel that I really do have to use it because having lived with Parkinson's for so long I think now is the time. We have the science, we have the research, and with those together we could diagnose Parkinson's earlier and then look at the inflammatory process far before the motor symptoms come in. And I think that's so important.

Joy Milne. And thanks to Joy, chemist Perdita Barran has been able to identity the cause of the altered smell profile, potentially leading us towards new ways to diagnose the disease as well as a better understanding of the mechanisms at play…

Purdita - What we found in the course of that was a really interesting thing, which was where the odour was strongest. And that was in regions of the body where there is more of a substance called sebum. Sebum is an oily, kind of greasy substance that we excrete everywhere. So what my team and I have done is to take swabs from the back of the neck and taken the sebum and looked at the molecules, the components within that sebum, and seen how they're different in people with Parkinson's and indeed people who are at the very early stages of Parkinson's compared to healthy individuals.

Chris - And what are the differences?

Purdita - If I was to swab a healthy person, I would see a particular signature, and if I was to swab someone with Parkinson's, I'd see another signature. And in a lot of our methodology, about 10% of the molecules we see are differently regulated. That means there's different amounts of them. Sometimes more, sometimes less, and consistently so in the people with Parkinson's and the people without. So we've actually got about 500 compounds that vary on the skin of people with Parkinson's from the skin of people who haven't got Parkinson's. And now our process is to try and use some of those to make a test that would allow us to confirm that someone has Parkinson's or not.

Chris - What do your instincts tell you about how far in advance of a person knowing they've got Parkinson's, that you begin to see these changes?

Purdita - So we've primarily focused on people who are what are called drug naive. So that means they've just had a clinical diagnosis from a neurologist, but they've not yet been treated with Parkinson's drugs. But we've recently done some work with a group in Vienna looking at people who have a related condition called REM sleep behaviour disorder. In those individuals we, in our measurement method - taking the seed from swabs, measuring with mass spectrometry, essentially weighing the molecules there, we see a distinct signature. Some of which is like Parkinson's signature and some of which is distinctive actually as its own stage of the disease. So we know that, in that cohort of people who have a very high likelihood of converting to Parkinson's, within a 10 year period, about 70% of them will, we can see early changes in their sebum that relate to progression of Parkinson's. We are currently doing a large study with a group in the USA looking at nurses who have got early symptoms of Parkinson's. And I hope to report on the results of that in the middle of next year. So we want to see how early these changes occur, why the changes occurring is something else we've been able to do. The molecules we look at are all metabolites, and those relate to biochemical processes that happen in all of our bodies. What we found is that in people with Parkinson's, a really important and really fundamental process that happens in our mitochondria, which is something called the carnitine shuttle, and it happens to give us more energy, actually it gives us energy to exist. It involves the import of long chain fatty acids into our mitochondria, and those are then used up to gain energy. We see that molecules involved in that process are downregulated and so we are less able to remove those long-chain fatty acids, and in fact we see more of them on the skin of people with Parkinson's. And we think that's related. So we are seeing fundamental dysregulation of several critical pathways within the cells of people with Parkinson's simply by taking a skin swab.

Chris - Do we know whether what you are seeing is cause or effect, though?

Purdita - There are two schools of thought with Parkinson's. People who believe it's a brain first disease, and those who believe it's a body first disease. I'm in the latter camp so far. We know that similar dysregulation occurs due to frailty. So some of this dysregulation is also seen in very elderly people. And to some extent, Parkinson's cells are cells that are ageing more rapidly than should happen to that individual. So we are pretty convinced, and there's good evidence from this where people who have genetic markers for Parkinson's have been screened, that the prodromal symptoms occur before there is significant damage to the brain. And why is another matter, but I am increasingly convinced that it is a metabolic effect that has happened. Sometimes due to genetic reasons and sometimes due to environmental reasons.