Grant Will Help Develop Non-Invasive Skin Test for Diagnosing Parkinson’s

Grant Will Help Develop Non-Invasive Skin Test for Diagnosing Parkinson’s

Scientist Wenquan Zou, MD, PhD, has received a two-year grant to develop a non-invasive skin test for diagnosing Parkinson’s disease, Alzheimer’s disease, and other neurodegenerative disorders.

Diagnosing these disorders currently requires invasive analysis, either by imaging brain tissue or analyzing the cerebrospinal fluid (CSF) — the liquid surrounding the brain and spinal cord — for disease biomarkers. These are biological substances that can be measured to indicate a medical condition or disease.

Changes associated with Parkinson’s, and other neurodegenerative diseases, begin to occur around two decades before people develop symptoms, researchers say. An earlier diagnosis could allow individuals to receive treatment early in the disease process.

In Parkinson’s, the accumulation of abnormal (misfolded) alpha-synuclein protein leads to the formation of toxic aggregates, or clumps, that in turn lead to the death of dopaminergic neurons. Those neurons are responsible for producing dopamine, a substance produced in response to nerve signals that acts as a chemical messenger.

These toxic clumps are the main component of Lewy bodies and Lewy neurites found in the brains of Parkinson’s patients.

The potential test could help identify those at risk for Parkinson’s by detecting the presence of misfolded alpha-synuclein proteins in the skin.

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“In addition to early diagnosis, pinpointing the misfolded proteins in more accessible specimens such as the skin can be used for effectively monitoring disease severity and evaluating the therapeutic value of new treatments for Alzheimer’s and other neurodegenerative diseases,” Zou, associate director of the National Prion Disease Pathology Surveillance Center, at Case Western Reserve University School of Medicine, said in a press release.

While certain lab tests and microscopy techniques can detect the presence of misfolded alpha-synuclein in the skin, these still have variable levels of sensitivity. That renders the diagnoses unreliable, make these inconsistent as diagnostic tools.

The proposed test uses a newly developed technology — called real-time quaking-induced conversion or RT-QuIC — to detect the presence of misfolded proteins in the skin.

In the new test, researchers mix a skin sample with the normal protein of interest, like alpha-synuclein. It is known that the presence of a misfolded protein can induce the aggregation of normal proteins. These clumps, in turn, trigger a fluorescent probe that emits a light that can be monitored in real time.

The skin test is highly sensitive and makes it possible to detect even small amounts of misfolded protein in the skin.

“Since skin biopsy is substantially less invasive than spinal tap [also called lumbar puncture, the invasive process to acquire a CSF sample] and brain biopsy, and because RT-QuIC is highly sensitive and specific and therefore more accurate than other lab-based methods, it is conceivable that the test represents a promising tool for diagnosing, characterizing, and predicting Alzheimer’s disease as well as Parkinson’s and other neurodegenerative diseases,” said Zou, also an associate professor in the departments of pathology and neurology at the Case Western School of Medicine in Ohio.

The same team had previously used the test to successfully detect misfolded proteins in the skin of people who died from Creutzfeldt-Jakob disease, sometimes called the human version of mad cow disease.

The new grant will allow the Zou and his team to confirm and extend these findings to Parkinson’s disease, and other neurodegenerative disorders.

Funding for the project is provided by the Alzheimer’s Association, Alzheimer’s Research UK, the Michael J. Fox Foundation for Parkinson’s Research, and the Weston Brain Institute. The grant award is for $149,729.00 over the course of two years.

Patricia holds a Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She has also served as a PhD student research assistant at the Department of Microbiology & Immunology, Columbia University, New York.
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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.
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Patricia holds a Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She has also served as a PhD student research assistant at the Department of Microbiology & Immunology, Columbia University, New York.
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