Scientists discover the chemicals behind the unique Parkinson’s smell


HIPPOCRATES, GALEN, Avicenna and other ancient physicians frequently used odour as a diagnostic tool. Although scent is not used nearly as often in modern medicine, it still has its place. Paramedics are routinely taught to spot the fruity smell on the breath of diabetics who have become hyperglycaemic and gastroenterologists are trained to detect the odour of digested blood. But there has been scant evidence of a smell associated with neurodegenerative disorders. Now one has been found for Parkinson’s disease.

Frequently causing tremors, rigidity and dementia, Parkinson’s is both debilitating and substantially shortens life expectancy. The rate at which these symptoms appear and worsen cannot be stopped or slowed yet but its most harmful effects can be staved off with drugs. As with many diseases, the earlier the intervention, the better. Yet herein lies one of the greatest challenges—there are no tests that diagnose whether Parkinson’s is actually present. The best that neurologists can do is study the symptoms and theorise about whether someone actually has the disease. Hence the search is on for a better form of diagnosis. Unexpectedly, scientists are now literally following someone’s nose.

Joy Milne, a retired nurse from Perth, Scotland has an extraordinary sense of smell. Known as hyperosmia, Mrs Milne’s condition allows her to detect odours that are imperceptible to most people. In 1974 Mrs Milne noticed an odd musky smell around her house that had not been present before. In 1986, her husband, Les Milne, was diagnosed with Parkinson’s. He lived with the disease for a number of years and while the symptoms were initially manageable with medication, this became harder over time. Eventually, he was forced to retire and, while attending Parkinson’s support groups, Mrs Milne noted something extraordinary. Everyone with the disease had the same distinctive odour that her husband had developed in 1974. It was shortly after that realisation that she started collaborating with researchers.

By providing Mrs Milne with shirts worn by Parkinson’s patients, researchers found she was able to identify that the smell was concentrated along the upper back, and not in armpits as previously assumed. Most remarkably, of the control subjects without the disease, Mrs Milne found one to have the musky odour. Nine months later that person was diagnosed with the disease.

All this led Perdita Barran of the University of Manchester, in Britain, to set out to discover what was producing the telltale odour that Mrs Milne could detect.

Previous work found that patients with Parkinson’s had a tendency to overproduce a waxy compound on the skin of their upper backs. Known as sebum, Dr Barran speculated that something trapped within this compound was producing the odour. Keen to find out, Dr Barran and her colleagues set up an experiment.

The team analysed sebum samples from 43 people suffering from Parkinson’s and 21 who were not. The sebum samples were collected on gauze and warmed to release any volatile compounds that might be found within them. Mass spectrometry and gas chromatography were then used to identify whether there were volatiles present and what they were. For a subset of the patient samples, Mrs Milne smelled the compounds before they entered the mass spectrometer and pressed a button when the distinctive odour was present.

As Dr Barran reports in ACS Central Science, the mass spectrometer identified four compounds, perillic aldehyde, hippuric acid, eicosane and octadecanal, in the vaporised sebum of the Parkinson’s disease patients that were at entirely different levels to those in the healthy group. To test whether these different levels of compounds were generating the smell that Mrs Milne was detecting, Dr Barran presented them to her and confirmed that they were, indeed, responsible for the musky odour.

While relatively small in size, Dr Barran’s experiment is the first to reveal the specific compounds that generate the unique smell of Parkinson’s. Assuming larger follow-up experiments replicate her findings, the work paves the way for the development of a device, a sort of electronic nose, that could sniff the upper backs of patients to quickly determine who has the disease and who does not. That would allow drugs to help mitigate the symptoms to be administered all the sooner.