A Scottish woman named Joy Milne made headlines in 2015 for an unusual talent: her ability to sniff out people with Parkinson’s disease, a progressive neurodegenerative illness that is estimated to affect about 10 million people worldwide. Since then, scientists in the U.K. have been working with Milne to pinpoint the molecules that give Parkinson’s its distinct olfactory signature. They have now zeroed in on a set of molecules specific to the disease—and created a simple skin-swab-based test to detect them.
Milne, a 72-year-old retired nurse from Perth, has hereditary hyperosmia, a condition that gives her hypersensitivity to smell. She discovered that she could smell Parkinson’s after noticing her husband, Les, was emitting a new, musky odor. When he was diagnosed with Parkinson’s many years later, she linked this change in scent to the disease. Les died in 2015.
In 2012 Milne met University of Edinburgh neuroscientist Tilo Kunath at an event organized by the research and support charity Parkinson’s UK. Though skeptical at first, Kunath and his colleagues put Milne’s claims to the test. They had her smell 12 T-shirts, six from people with Parkinson’s and six from nonaffected individuals. She correctly identified the disease in all six cases—and the one T-shirt from a healthy person she categorized as having Parkinson’s belonged to someone who was diagnosed with the disease less than a year later.
Kunath, along with University of Manchester chemist Perdita Barran and their colleagues, subsequently used mass spectrometry to examine sebum (an oily substance found on the surface of the skin) from people diagnosed with Parkinson’s. They found molecular changes suggesting alterations in the metabolism of fatty molecules known as lipids.
In Barran’s latest study, published in the American Chemical Society journal JACS Au, she and her colleagues developed a simple skin-swab-based test to detect Parkinson’s molecular signature. By comparing sebum samples from 79 people with and 71 people without the illness, the team zeroed in on a set of large lipids. These compounds could be spotted in a matter of minutes using a special type of mass spectrometry in which technicians use a piece of paper to rapidly transfer substances from a swab to an analyzer.
“I think it’s a very promising set of biomarkers,” says Blaine Roberts, a biochemist at Emory University, who wasn’t involved in the work. He adds that one of the big open questions is how exacting this test can be. The authors of the new study reported the detailed chemical profile of the unique Parkinson’s signature, but they did not include an assessment of accuracy. According to Barran, as yet unpublished data suggest that their test may be more than 90 percent accurate in determining whether a person has Parkinson’s.
Tiago Outeiro, a neuroscientist at the University of Göttingen in Germany, who was not involved with the research, says the sebum-based swab test is novel. He adds that one clear advantage it has over other methods—such as blood tests—that probe for Parkinson’s biomarkers is the ease of sample collection. Outeiro wonders whether people with diseases that share symptoms and pathologies with Parkinson’s, including multiple system atrophy, also have similar chemical markers.
The researchers are now working with local hospitals to ascertain whether their sebum-based test can also be conducted in clinical laboratories—a key step toward determining whether it would work as a diagnostic tool. Ultimately, Barran says, the researchers hope to use the test to help secure a faster diagnosis for individuals with suspected Parkinson’s who have been referred to neurologists by a general practitioner. Thousands of such people are currently waiting to see neurologists in the U.K.’s National Health Service, for instance, and it will take an estimated two years to clear that list, Barran says. The new tool could let those patients mail in skin swabs to be analyzed in a hospital lab, pinpointing those who need help most urgently. Barran’s research team is approaching people on the waiting list to see if they are willing to take part in a trial of this triage process.
Barran and her colleagues are also collaborating with researchers at Harvard University to determine whether sebum-based biomarkers are detectable in people who have unexplained constipation, a reduced sense of smell or other possible early signs of Parkinson’s but have not yet received a diagnosis.
Milne has also inspired other scientists to search for biomarkers based on the disease’s olfactory signature. Last year investigators in China published a paper describing an electronic nose—an artificial-intelligence-based sensor modeled after the olfactory system—that sniffs out a set of nonlipid molecules present in the sebum of patients with Parkinson’s. Other groups in China, the U.K. and elsewhere have been training dogs to sniff out the disease.
And Parkinson’s may not be the only disease Milne has a nose for. She has also reported noticing unique smells in people with Alzheimer’s, cancer and tuberculosis, and she is working with scientists to see whether specific olfactory signatures of those diseases can be identified.
Milne says she hopes this research will ultimately benefit patients with these conditions. “My husband suffered from [Parkinson’s] for 21 years after his diagnosis, but he had it many years before that,” Milne told Scientific American in 2015. “I would like to see that people don’t suffer the way he suffered.”