Novel Skin Test Shown to Predict Development, Monitor Progression of Parkinson Disease

March 16, 2021
Matthew Gavidia
Matthew Gavidia

Matthew is an associate editor of The American Journal of Managed Care® (AJMC®). He has been working on AJMC® since 2019 after receiving his Bachelor's degree at Rutgers University–New Brunswick in journalism and economics.

A novel skin test was shown to detect metabolites that could predict the development of Parkinson disease, as well as delineate changes in lipid processing and mitochondria that can be leveraged to better understand how the disease develops.

With no definitive test to diagnose Parkinson disease (PD) without postmortem autopsy, patients are often misdiagnosed or spend extended time going through various tests, such as long walks, that can prove uncomfortable. For a progressive disease such as PD, this lost time can have a substantial impact on patient care. Thirty-four percent of misdiagnosed patients reported a decline in health in a recent poll.

Recent studies have shown the possibility that PD may be detected through the skin. One study of a skin test to detect clumping of alpha-synuclein, an abnormal protein suggested to have a central role in the pathogenesis of PD, showed it was feasible to do so with high sensitivity and specificity, although a small cohort of 25 patients with PD and 25 controls was used for the analysis.

Researchers of a recent study published in Nature Communications sought to further examine this potential diagnostic breakthrough, instead using a metabolomics profiling approach to identify changes to lipids in PD observed in sebum, a noninvasively available biofluid.

“Seborrheic dermatitis is a common nonmotor symptom reported in up to 60% of people with PD,” explain the study authors. “This condition presents as ‘oily skin’ that correlates to an excess of sebum, produced and secreted by the sebaceous glands in the dermis of the skin.”

Utilizing high-resolution liquid chromatography-mass spectrometry, the researchers analyzed 274 samples of sebum derived from the upper backs of participants, including drug-naive patients with PD (n = 80), medicated patients with PD (n = 138), and well-matched controls (n = 56). Participant samples were profiled for the complex chemical sebum marker present in people with PD, with the analysis also assessing fundamental changes in the sebum as the condition progresses.

Ten chemical compounds in sebum known to be elevated or reduced in people with PD were examined, with results presenting with 85% accuracy.

In their findings, skin samples of patients with PD were shown to have metabolites that could predict PD phenotype. Moreover, a pathway enrichment analysis found that those with PD exhibited changes in lipid processing and mitochondria, a known hallmark of PD, indicating that the skin test may not only work to diagnose the condition but to also monitor how it develops over time.

Alterations in lipid metabolism were shown to be related to the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism, and fatty acid biosynthesis.

"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,” said study author Perdita Barran, BSc, Hons PhD, professor of mass spectrometry at The University of Manchester, in a statement.

Through uncovering the presence of lipid dysregulation and its link with altered mitochondrial function in patients with PD, the researchers say that results can help to better develop new tests and assess efficacy of new therapies in slowing, stopping, or reversing progression of PD.

“We are now looking to take our findings forward to refine the test, to improve accuracy even further, and to take steps towards making this a test that can be used in the [National Health Service] and to develop more precise diagnostics and better treatment for this debilitating condition," said Barran.

Reference

Sinclair E, Trivedi DK, Sarkar D, et al. Metabolomics of sebum reveals lipid dysregulation in Parkinson’s disease. Nat Commun. Published online March 11, 2021. doi:10.1038/s41467-021-21669-4