The Sequence 6/17-6/23

Sniffing Out Parkinson's: New Tools for Early Detection

Revealing the Faces and Voices of Parkinson’s Disease; Illustration by Randell Pearson for PD Movers, supported by Columbia University Department of Neurology

Sniffing Out Parkinson's: New Tools for Early Detection

Parkinson’s disease (PD) is a movement disorder characterized by stiffness and trembling of the arms and legs that eventually affects one’s ability to walk, talk, and perform simple tasks. It is the second-most prevalent neurodegenerative disease after Alzheimer’s. It is known to be quite treatable, yet the existing therapies address only the symptoms and aren’t able to stop the progression of the disease or reverse its damage to the brain. In fact, PD is still diagnosed essentially as it was 200 years ago, on the basis of its characteristic motor symptoms. This means that diagnosing PD earlier could allow for a disease therapy to have a more meaningful shot at treating the disease itself and not just its symptoms, before neurons in the brain have already died at the hands of PD.

Today we focus on updates in diagnosing and treating PD using various types of early detection technology and immune therapies. We’ll discuss the newly identified biomarkers that are associated with PD that can help in early detection, progress on immune therapy research, and what clinical value it all has for patients with PD.

What are the new ways of detecting Parkinson’s disease?

One of the new ways to detect PD is by smell; at least for individuals that are “hyperosmic”,or have a heightened sense of smell like Joy Milne. Joy participated in a small pilot study in Edinburgh led by Tilo Kunath, a professor at the University of Edinburgh, in order to see whether she would be able to differentiate fabric samples worn by individuals with and without PD. In other words, would she be able to smell Parkinson’s?

It turns out, she could. Remarkably, she was able to correctly identify all the Parkinson's patients by smell. Not only that, but the one ‘false positive’ in the experiment, i.e. a control that Joy had incorrectly identified as a Parkinson’s patient, was diagnosed with PD nearly a year after the experiment was conducted. In follow up studies, the team realized the smell was coming from sebum, the lipid-rich substance secreted by the skin. In people with Parkinson's, sebum seems to have different chemicals than in those without. In correlating the molecular fragments making up the sebum of PD patients with Joy’s reportedly positive samples, they found that Joy reported a strong Parkinson’s-like scent in the presence of three chemicals: eicosane and octadecanal, which are known to have weak waxy or oily smells, and hippuric acid, which is not typically reported to have any smell at all. Joy might have been picking up on these distinct molecules, like a super sniffer detecting a unique fingerprint of the disease.

Another new way to detect PD is by testing for biomarkers in the blood. With the help of proteomic profiling and machine learning, an international team led by investigators in the UK and Germany has identified a handful of blood plasma proteins associated with subsequent Parkinson's disease development, pointing to the possibility of developing blood-based biomarkers for the progressive neurodegenerative condition.

Using mass spectrometry to analyze blood samples from people with and without Parkinson's, they found eight proteins whose levels differed significantly between the two groups. In clinical application, this test will include a panel of these eight biomarkers that can distinguish early PD from healthy controls. The test uses a pipeline looking at a multiplexed panel of proteins together with machine learning to assess for multiple biomarkers to create a final risk assessment. This is in contrast to the assessment of just a single biomarker which is the typical approach for many biomarker tests. This could be a major breakthrough in helping people get the care and treatment they need sooner; in experiments, the test indicated changes in the blood that could be identified up to seven years before symptoms even appear.

What treatment is available for Parkinson’s?

PD is caused by the accumulation of a protein called alpha-synuclein protein (a-syn), which causes the degeneration of neurons that produce dopamine. That being understood, treatments for PD typically target either the toxic a-syn protein build-up, or the loss of dopamine. Right now, treatment for those with PD typically begins with L-DOPA, an amino acid that gets converted to dopamine in the brain and has now been the standard of care in PD for 60 years. Although extremely well tolerated, the efficacy of L-DOPA fluctuates over time. There are also treatments which target the toxic build-up of the a-syn protein instead of the resulting dopamine deficiency. I wrote about one such treatment in this previous Sequence newsletter.

Last week, researchers published the details of a small trial that could lead to another a-syn protein targeted treatment as well as a new method of diagnosis. Vaxxinity, a US-based biotech company, created a vaccine that trains the immune system to attack only abnormal versions of a-syn—which are improperly folded—and not the regular forms. The company also worked with researchers at the University of Texas to develop a diagnostic test that measures levels of the abnormal protein in a patient's cerebrospinal fluid. The test could be a crucial step for helping diagnose Parkinson's, which often gets misdiagnosed.

What’s the takeaway?

This article highlights the exciting advancements in PD detection and treatment. Researchers are looking beyond the traditional motor symptoms for earlier diagnosis, and new methods even include sniffing out the disease through a heightened sense of smell to identify protein changes. Our new understanding of molecular changes that alter the smell of the body, biomarkers that can be detected earlier, as well as new methods for potential treatment could provide hope to the approximately 500,000 people in the US who are diagnosed with Parkinson's. Together, this could mean detection of the disease at an earlier stage when treatment is more effective.

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Newsletter Sources:

1. Image: https://www.neurology.columbia.edu/file/1518/download?token=kcHPdnW7

2. https://medlineplus.gov/parkinsonsdisease.html

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