LONDON – New research shows it is possible to diagnose Parkinson’s disease by mass spectrometry analysis of sebum samples taken with a simple skin swab, and that the same technique has potential to be used for diagnosing COVID-19.
In a paper published in Nature Communications on March 11, 2021, scientists and clinicians in the U.K. and the Netherlands describe using high resolution mass spectrometry to profile the chemical signature of lipids and other biomarkers in sebum from Parkinson’s patients and show how these exhibit subtle but fundamental changes as the disease progresses.
Separately, as a pandemic-inspired extension of this work, the researchers reported in a preprint in Eclinical Medicine how they have found evidence that COVID-19 infection also leads to changes in the composition of sebum. They say this could form the basis of a new type test for COVID-19 that would be easier to administer than lateral flow tests, while being as accurate as PCR testing.
A spinout company, Manchester, U.K.-based Sebomix Ltd., has been formed and is now looking for funding to commercialize the technology.
“The test is scalable, and our aim now is to make this targeted Parkinson’s disease diagnostic clinically available,” said Perdita Barran, professor of mass spectrometry at Manchester University, who led the project. The test takes “Three to four minutes per sample” to run and with the existing installed base of mass spec machines it would be possible to provide an earlier, definitive diagnosis, and to monitor progression over the long running course of the disease, Barran said.
At present, diagnosis of Parkinson’s mainly relies on observation of the decline in motor function, a symptom that occurs only when the condition has advanced and there already is significant depletion of dopaminergic neurons.
The current gold standard diagnostic test, Datascan, involves the injection of a radioactive tracer to marks neuronal cells in the basal ganglia that carry dopamine transporters. There is a four to five hour wait after administration of the tracer before a radiology scan, which takes 45 minutes to complete.
In contrast, sebum skin swabs from the top of the back are simple and easy to take and can be transported at ambient temperatures, with no need for fixing. During COVID-19 lockdown restrictions, some of the participants in the study took their own swabs at home.
“Sebum acts as a preservative. You find the features of Parkinson’s disease irrespective of the temperature and the length of the journey,” said Barran. “Not only is the test quick, simple and painless, but it should also be extremely cost effective, because it uses existing technology that is already widely available.”
Barran told BioWorld “the big goal” is to push the diagnosis and treatment to earlier in the disease. “We want to remove the burden of misdiagnosis, so people get appropriate treatment sooner,” she said.
The project has a fascinating history, having originated in the observation of “super smeller” Joy Milne, whose husband was diagnosed with Parkinson’s disease at the age of 45. Milne had noticed a different smell on her husband from well before the diagnosis.
Excess production of sebum is known to be one of the early non-motor symptoms of Parkinson’s. Barran said others have remarked on noting a distinctive smell on bedding and clothing, even after laundering.
However, beyond dermatological conditions, such as acne, this biofluid, a lipid rich substance composed of triglycerides, fatty acids, wax esters, squalene, and cholesterol, has rarely been used in disease diagnostics.
Inspired by the Parkinson’s research, Barran and colleagues have done initial tests to see if the technique reads across to COVID-19 infection. COVID-19 has been reported to cause a wide range of metabolic dysregulation, detected in blood and breath, suggesting that the disruption of normal metabolism could extend to the skin.
In the pilot study of 67 participants reported in Eclinical Medicine, dysregulation of the profile of sebum lipids was observed in people who were COVID-19 positive. Levels of sebum triglycerides, in particular, were depressed in cases of the disease. In addition to illustrating the level of metabolic information available from sebum, it suggests potential for it to be investigated as a means of diagnostic testing, the researchers say.
As an example of the additional value of sebum analysis, in Parkinson’s disease lipid dysregulation was linked to the altered mitochondrial function that is one of the hallmarks of the condition. Barran said this could point the way to new drug targets for the neurodegenerative disease.
“How lipid metabolism is regulated is fundamental [to Parkinson’s]. Cells can’t make energy in quite such an efficient way,” she said. Barran also expects the test to be of use in stratifying patients in clinical trials and for monitoring response to experimental drugs.