A team of researchers has developed technology that can detect symptoms of Parkinson’s disease in urine samples. This approach allows researchers to assess whether LRRK2 (leucine-rich repeat kinase 2) proteins and their downstream pathways were altered in Parkinson’s disease patient samples.
This technology could potentially lead to widespread non-invasive testing for other neurological diseases besides cancer. “We believe this is a logical and rational approach to moving forward in the diagnosis of Parkinson’s disease,” said W. Andy Tao, professor of biochemistry at Purdue.
“Diagnosis of this type of neurodegenerative disease is difficult.” Cognitive and movement testing can take a year or more to confirm a diagnosis, so molecular tests for early diagnosis and intervention can help people with Parkinson’s more quickly, he explained.
Tao and eight co-authors from Purdue, Tymora, The Michael J. Fox Foundation for Parkinson’s Research and Columbia University published their findings in the journal Communications Medicine.
Parkinson’s disease alone affects an estimated 1% of the population
“This is going to be a big new area in the development of diagnostics,” predicted co-author Anton Iliuk, president and chief technology officer of Tymora, “especially for neurodegenerative diseases and cancer.”
Parkinson’s disease alone affects an estimated 1% of the population over the age of 60. Up to one million Americans live with the disease, and 90,000 new cases are diagnosed each year.
The project began several years ago after Padmanabhan read some of Iliuk and Tao’s work on the EVtrap (total recovery and purification of extracellular vesicles) method for urine analysis and proposed a collaboration.
“When I was looking at the data from their previous publication,” said Padmanabhan, “it was interesting to note the expression of an important protein associated with Parkinson’s disease, LRRK2. This piqued my interest because this approach gave us the opportunity to see if LRRK2 proteins or the downstream pathways they affect are indeed altered in urine samples from Parkinson’s patients who have a mutation in the gene.
In 2017, Tao led a team that developed a blood test that could realistically detect breast cancer. In this work, Tao and his colleagues compared samples taken from breast cancer patients and a healthy control group.
“We identified phosphorylated proteins that are a hallmark of cancer,” Tao said. And inside these proteins, the team found extracellular vesicles, small packages that cells use as their molecular transport system. The finding demonstrated that a blood sample yielding phosphoproteins could serve as a potential marker for early cancer diagnosis or to monitor disease progression.
The team was able to rapidly isolate vesicles from urine samples using the EVtrap method developed by Tymora.
“We’ve used the method for a number of indications, primarily focusing on different cancers for biomarker discovery and validation,” said Iliuk, who earned his doctorate in biochemistry from Purdue in 2011. Iliuk and Tao co-founded Tymora Analytical, which specializes in technology and services for the detection of disease biomarkers in biofluids.
“This kind of analysis opens a new frontier in the development of non-invasive diagnostics. It shows that biomarkers that were previously thought to be undetectable have been discovered and are doing a really good job of differentiating disease from a non-disease state,” Iliuk said.
After being exported from the brain to the bloodstream, they are concentrated or filtered into the urine. But collecting such biomarkers from the brain using a spinal tap is a highly invasive procedure.
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