Crying out for a new biomarker

The hunt for a biomarker for Parkinson's has led researchers to investigate a lot of different bodily fluids and techniques! A biomarker is a test that can diagnose Parkinson's, at the moment the only way to diagnose Parkinson's is by using your eyes and your ears. Previously people have tested blood, CSF (the fluid around your brain), skin, saliva, MRI scans, skin samples and even samples of colon. But this pilot study is about a potential location for a biomarker that I had not yet heard of: Tears.

Its well known already that people with Parkinson's have reduced amounts of tears and a lower blink rate. And the researchers point out the the nerves that control the tear gland (lacrimal gland) connect to the brainstem. The brainstem is where a lot of the changes in early Parkinson's take place.

In this study they took 36 people with Parkinson's and 18 healthy people without Parkinson's and collected their tears by using some filter paper to absorb them. They then extracted the proteins from the collected tears.

They found that the Parkinson's participants had a smaller volume of tears but the protein concentration in the tears was about the same as healthy controls. They also identified 21 proteins that people with Parkinson's had significantly higher amounts of and 19 that were significantly reduced in Parkinson's too.

This is only a very small pilot study so we need some further studies in larger groups of patients before we draw any conclusions. But tears are a very attractive biomarker simply because they are so accessible. So this is definitely one to keep in mind and watch out for any further studies about.

Parkinsonism Relat Disord. 2019 Mar 6. pii: S1353-8020(19)30094-X. doi:

Proteomic analysis of tear fluid reveals disease-specific patterns in patients with Parkinson's disease - A pilot study.

Boerger M¹, Funke S², Leha A³, Roser AE⁴, Wuestemann AK⁵, Maass F⁶, Bähr M⁷, Grus F⁸, Lingor P⁹.

Abstract

BACKGROUND:

The diagnosis of Parkinson's disease (PD) is still challenging and biomarkers could contribute to an improved diagnostic accuracy. Tear fluid (TF) is an easily accessible body fluid reflecting pathophysiological changes in systemic and ocular diseases and is already used as a biomarker source for several ophthalmological disorders. Here, we analyzed the TF of patients with PD and controls (CTR) to describe disease-related changes in TF and identify putative biomarkers for the diagnosis of PD.

METHODS:

Unstimulated TF samples of a pilot cohort with 36 PD patients and 18 CTR were collected via Schirmer tear test strips and then analyzed via a Bottom-up liquid chromatography electrospray ionization tandem mass spectrometry (BULCMS) workflow, followed by functional analysis encompassing protein-protein interaction as well as cellular component and pathway analysis.

RESULTS:

BULCMS analysis lead to the identification of 571 tear proteins (false discovery rate, FDR < 1%), whereby 31 proteins were exclusively detected in the PD group and 7 only in the CTR group. Whereas 21 proteins were significantly increased in the PD versus CTR groups, 19 proteins were significantly decreased. Core networks of proteins involved in immune response, lipid metabolism and oxidative stress were distinctly altered in PD patients.

CONCLUSIONS:

To our best knowledge, this is the first description of TF proteome in PD patients. Tear protein level alterations suggest the contribution of different disease-related mechanisms in ocular pathology in PD and propose candidate proteins to be validated as potential biomarkers in larger cohorts.

Gout again.. and is work affected by early Parkinson's?

After my positive blog-post on uric acid a while ago, we have another reminder that unfortunately in research things are often not so simple, especially when moving from observational findings to affecting real-world changes. We are ending the year with another negative trial in Parkinson's - it's recently been announced that the trial of urate-elevating drug Inosine is ending early as the investigators don't believe that the trial will achieve it's stated goal of slowing progression of Parkinson's. Alastair's paper on the causal relationship between urate levels and Parkinson's https://www.ncbi.nlm.nih.gov/pubmed/30014513 gave us a hint that uric acid, while associated with reduced risk, may not be directly causing this - so it's still important to understand more about these relationships and it will be instructive to read about the data that has been collected when this is published next year.

Talking of real-world impact, this interesting paper below explored the very real impact of early symptoms of Parkinson's disease on the workforce. At PREDICT-PD we are fascinated by what happens in the years before diagnosis of Parkinson's - a lot has been published on non-motor symptoms such as constipation, depression and sleep disorders - but not much on how this affects specific activities such as work. They looked at patients with Parkinson's who had to take sick leave and compared them to people who had taken sick leave for other reasons. Those with Parkinson's sick leave were more likely in the preceeding 5 years to have taken sick leave for reasons other than Parkinson's and more likely to have taken sick leave for musculoskeletal issues in particular. Given that the study was only able to look at sick-leave episodes exceeding 14 days, it illustrates the significant impact that these symptoms are having on patients in the early disease and even before diagnosis.

On a more positive note as we look towards the end of the year and Christmas, we are very pleased that recruitment is ramping up for the next stage of the PREDICT-PD project. We are working towards new publications of our own data in the coming months and we'd like to thank all for their ongoing support. If you or any family members are interested, please do have a look on www.predictpd.com.

Reduced workforce participation 5 years prior to first Parkinson’s disease sick-leave 

Jonathan Timpka, Örjan Dahlström, Armin Spreco, Maria H. Nilsson, Susanne Iwarsson, Toomas Timpka & Per Odin
https://www.nature.com/articles/s41531-018-0072-2 

Wishing you all the best over the festive season.

-anna