Analyzing the Scent of Parkinson Disease Could Lead to Diagnostic Tool

Volatile biomarkers of Parkinson disease (PD) could be identified through analysis of the chemical composition of sebum, as well as the smell, according to a study in ACS Central Science.

While a great amount research has been devoted to the study of the disease, no diagnostic test currently exists. Clinicians have previously diagnosed PD by observation of symptoms but can’t begin treatment until specific motor signs appear. The disease has a deteriorative effect on nervous tissues nearly 6 years before any symptoms can be shown.

“Identification and quantification of the compounds that are associated with this distinctive PD odor could enable rapid, early screening of PD as well as provide insights into molecular changes that occur as the disease progresses and enable stratification of the disease in the future,” researchers said.

The study was aided by Joy Milne of Perth, Scotland, a “Super Smeller” with a much stronger sense of smell than the average person. She previously identified a “musky” odor coming from her husband years before he was diagnosed with PD.

Participants of the study were randomly selected from 25 National Health Service clinics in the United Kingdom. Researchers measured volatile organic compounds in 2 cohorts. The “discovery” cohort had a total of 30 participants while the “validation” cohort had 31. A third cohort of 3 untreated PD participants was used for gas chromatography-mass spectrometry analysis, aided by the Super Smeller with the use of an odor port on the testing device.

Researchers gathered samples by swabbing participants on the upper back or forehead, the areas of highest sebum production in PD patients, with medical gauze. The samples were then sealed in background-inert plastic bags, transported to a central facility, and frozen until they were tested and analyzed.

Mass spectrometry was used to analyze sebum samples and identify levels of chemical compounds that were different in people with PD.

Researchers conducted chemical analysis on the sebum of individuals with PD and set their focus on 3 compounds of particular interest, which were hippuric acid, eicosane and octadecanal. The presence of these compounds was consistent with the specific “musky” smell of PD, confirmed by the Super Smeller after presentation of laboratory-prepared samples in a controlled olfactory environment. The presence of these compounds differed in people with PD and individuals without the disease.

“These potential explanations for the change in odor in PD patients suggest a change in skin microflora and skin physiology that is highly specific to Parkinson’s disease,” researchers said.

Seborrhea, a nonmotor symptom of PD, is a condition that causes overproduction of sebum, an oily substance secreted by the sebaceous glands that helps moisturize the skin and hair. Toxic forms of the protein alpha-synuclein, which is a signature molecule of PD, have been found in the skin of patients with PD.

Researchers suggest that a larger study, that gathers extended olfactory data from both human and canine smellers, along with headspace analysis, should be the next step in further characterizing the volatilome of PD sebum. They believe it could lead to the creation of a panel of volatile biomarkers associated with PD, create new methods for stratification, and eventually lead to the possibility of noninvasive screening for early diagnosis of PD.

“Finding changes in the oils of the skin in Parkinson’s is an exciting discovery,” Dexter said. "More research is needed to find out at what stage a skin test could detect Parkinson's, or whether it also occurs in other Parkinson's related disorders, but the results so far hold real potential to change the way we diagnose the condition and may even help in the development of new and better treatments for the 145,000 people living with Parkinson's in the UK.”

Reference

Trivedi DK, Sinclair E, Xu Y, et al. Discovery of volatile biomarkers of Parkinson’s disease from sebum [published online March 20, 2019]. ACS Cent Sci. doi: 10.1021/acscentsci.8b00879.