Smell Test Offers Hope of Early Parkinson's Diagnosis

Liam Davenport

November 05, 2015

A test based on the smell of someone's skin may allow the early diagnosis of Parkinson's disease, say United Kingdom (UK) researchers who have launched a study to investigate chemicals secreted by patients with the disease.

The study was inspired by a "super smeller" who detected a distinct odor on the skin of her husband, who had Parkinson's disease, that was strongest both before he was diagnosed and toward the end of his life.

The smell was subsequently detected in a small pilot study, and now it is hoped that, if this is replicated in a 200-strong controlled study, it could lead to a test that could offer early diagnosis of Parkinson's disease and monitoring of disease progression.

The research is led by Perdita Barran, PhD, professor of mass spectrometry and director of the Michael Barber Centre for Collaborative Mass Spectrometry, University of Manchester, UK, and is funded by the charity Parkinson's UK. The as-yet unpublished findings were released by the university.

Speaking to Medscape Medical News, Dr Barran underlined that there is currently no diagnostic test for Parkinson's disease, and the only current method is to perform brain imaging, which identifies patients at a typically more advanced stage.

"Early diagnosis may allow us to treat people early, which may slow down the progression of the disease at a state when it still could allow people to have a better outcome," she said.

She added: "The other thing is we may be able to monitor the progression of the disease better and more effectively, and we may find out something about the biochemical pathways that cause the disease, at a stage that we don't yet know about."

Joy Milne, left, and Dr Perdita Barran. Courtesy University of Manchester

The project began when Joy Milne, whose husband died of Parkinson's disease earlier this year, approached Tilo Kunath, PhD, a Parkinson's UK fellow at Edinburgh University, at a Parkinson's outreach event. She asked Dr Kunath whether people with the condition smell differently from other people, as she had detected a smell on her husband.

This prompted Dr Barran and Dr Kunath to conduct a small study in which six patients with Parkinson's disease and six individuals who knew them were asked to sleep in prewashed t-shirts overnight.

The t-shirts were cut in half and anonymously bagged to give 24 samples, and Milne was asked to identify the ones worn by people with Parkinson's disease. She was correct in 11 of 12 cases, having identified all 6 patients with Parkinson's disease. The false-positive that she identified went on to develop Parkinson's disease approximately 9 months later.

In parallel to that study, Dr Barran and her team extracted the volatile compounds from the t-shirt material and were able to identify the molecular signature that singled out people with Parkinson's disease from controls.

However, the study was too small to permit any definitive conclusions, so now Dr Barran and colleagues in Edinburgh and London have secured funding to recruit approximately 200 people to a study in which state-of-the-art mass spectrometry technology will be used to analyze skin swabs.

To rule out the possible effects of treatment on secretion of the molecular signature, the study will involve around 50 people with treatment-naive Parkinson's disease; 50 with more advanced disease who are receiving treatment; 50 patients with seborrheic dermatitis (which is common in Parkinson's disease); and 50 controls matched for age, body mass index, and sex.

While Dr Barran has a sense of the composition of the molecular signature, she emphasized that the research is still at an early stage. She said, "We haven't squared the circle, we haven't isolated those compounds and/or synthesized them such that we can come back to Joy or indeed other people and see whether they smell."

"What we have done is we've found that there is a distinction, but the distinction is between people who have late-stage Parkinson's and people who don't. We don't know whether that is an odorous compound yet, first off, and we also don't know whether that's the right control group for what Joy can smell."

"But in terms of the molecular type, it is a molecule that's been fairly hydrophobic and may be dissolved in oily material."

An interesting outcome of announcing the research has been that around 20 people have come forward to tell Dr Barran that they noticed a change in the smell of their partners or relatives or friends, and at an early stage, which tallied with Joy Milne's experience.

"Both Joy and her husband noticed the smell change about 5 or 6 years before he was diagnosed," Dr Barran said.

She added: "What's quite clear from what Joy and other people have said is it's stronger when the symptoms are less well controlled — so either at early stages, when the symptoms are less well controlled, or at later stages, when the drugs aren't working as well."

"That's quite interesting because it indicates that we will be able to use this not just as an early diagnostic signature but also potentially as something for monitoring the efficacy of therapy."

She concluded: "Going forward, if we want to develop a test that is cheaper and more of a yes/no test than doing the mass spectrometry that we will do, then we've already got some ideas of how to do that."

Preliminary Evidence

Approached for comment, Anna DePold Hohler, MD, assistant dean, Office of Clinical and Strategic Affiliations and associate professor of neurology, Boston University School of Medicine, Massachusetts, described the research as "interesting."

Speaking to Medscape Medical News, she said that while the study is preliminary, "it looks like they'll be taking it to further levels now in terms of trying to evaluate more patients and see there's if there's indeed some type of marker, a smell marker, on the skin surface that could be used to detect Parkinson's."

She continued: "What we've known for a while with Parkinson's disease is you can see signs in terms of the different parts of body."

"The skin has long been known to be affected in terms of changes in the oiliness of the skin, and some people have flaky changes in the skin...there's also smell that goes along with it and it could be potentially useful in terms of an early detecting biomarker, so to speak, for Parkinson's disease."

Dr Hohler pointed out that previous studies have looked at the skin, alongside other areas of the body, such as the gut environment, that could be altered in patients with Parkinson's disease.

She said, "If there's some way to detect the disease in a part outside of the brain that's more easily accessed, it would be a very wonderful thing."

"We're also looking at biomarkers in blood and spinal fluid right now to try and find something that can be used as an early detection."

Dr Hohler also underlined the importance of early detection to halt or slow down the disease process, to avoid some of the motor and more advanced features of the condition.

"Currently, we're probably losing 5 to 10 years in terms of time might where we might be able to intervene in people with Parkinson's disease, so it's a significant amount of time that we're losing," she said.

No funding was received for the study. The authors have disclosed no relevant financial relationships.


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