Particular Skin Smell May Help in Early Parkinson’s Diagnosis, Study Suggests

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by Alice Melão |

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Parkinson’s disease (PD) could be identified through a noninvasive analysis of chemical components of sebum, the oily substance that helps keep skin and hair moisturized, a pilot study suggests.

The study, “Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum,” was published in the journal ACS Central Science.

In the early ages of medicine, a person’s odor was commonly used to help identify diseases. Although this method is no longer used, modern medical studies have associated some illnesses, in particular metabolic and infectious diseases, with specific smells.

One of the study’s co-authors, Joy Milne, the wife of a Parkinson’s patient who was diagnosed in 1986, has an extremely sensitive sense of smell, called a super smeller, and is able to recognize a particular odor associated with Parkinson’s disease. In preliminary tests, she identified this odor mainly in areas of high sebum production, such as the upper back and forehead.

Overproduction of sebum by skin sebaceous glands (a condition known as seborrhea) is a well-known non-motor symptom of the disease, and toxic forms of the protein alpha-synuclein — a Parkinson’s molecular hallmark — have been found in the skin of Parkinson’s patients.

“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,” the researchers wrote.

The team, led by researchers at the University of Manchester, further explored the potential of using smell and sebum analysis as a diagnostic tool for Parkinson’s disease.

They analyzed the volatile chemical components of sebum samples collected from 43 Parkinson’s patients and 21 healthy volunteers who were recruited at 25 clinical sites across the U.K.

These volatile components, which are often associated with odors, were detected by high-throughput chemical analysis as well as by olfactory pattern analysis, with the help of Milne.

Among the 17 particular compounds detected in Parkinson’s patients the team found 3,4-dihydroxy mandelic acid, which is a metabolite of L-dopa — one of the most commonly prescribed medications for Parkinson’s disease.

However, this compound was also identified in untreated patients. These findings suggest that changes in this compound could be indicative of other mechanisms rather than just therapy metabolism.

Further analysis revealed that the compounds perillic aldehyde and eicosane were significantly different between Parkinson’s patients and healthy controls. Perillic aldehyde levels were lower in Parkinson’s samples, while eicosane was present at significantly higher levels than in controls.

The presence of these compounds was consistent with the olfactory patterns of the specific “musky” smell of Parkinson’s.

Next, the team asked Milne to try to validate different mixtures of the identified compounds and compared them between patients and controls.

A mixture of all 17 identified compounds, or specific combinations of just nine or four of these compounds, were identified as being closer to the smell of Parkinson’s patients than healthy individuals.

These results were maintained regardless of whether patients had taken Parkinson’s medications or not.

“Now we have proved the molecular basis for the unique odor associated with Parkinson’s we want to develop this into a test,” Perdita Barran, PhD, a professor at the Manchester Institute of Biotechnology and senior author of the study, said in a press release.

“This could have a huge impact not only for earlier and conclusive diagnosis but also help patients monitor the effect of therapy. We hope to apply this to at risk patient groups to see if we can diagnose pre-motor symptoms, and assist with potential early treatment,” she added.

Main differences in perillic aldehyde and octadecanal levels could be associated with changes in fatty molecule metabolism in Parkinson’s disease. But they may also indicate altered activity of the natural bacteria that populate the skin of Parkinson’s patients.

“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,” the researchers wrote.

More studies are still needed to further explore the potential of these volatile Parkinson’s biomarkers. In addition, studies with extended olfactory data from human smellers, as well as canine smellers, may help characterize in more detail the sebum odor pattern linked to Parkinson’s.

“Finding changes in the oils of the skin in Parkinson’s is an exciting discovery,” said David Dexter, PhD, deputy director of research at Parkinson’s UK. “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.”

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