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Funded Studies

RT-QuIC Testing of Misfolded Alpha-synuclein in S4 Study Samples

Study Rationale:
The protein alpha-synuclein is vital to normal brain function. In Parkinson's disease, alpha-synuclein misfolds, forming aggregates, or clumps, that impair the ability of brain cells to function. Discovering a biological marker (biomarker) that can be safely sampled from blood, other body fluid or peripheral tissue biopsies (such as the salivary gland or cerebrospinal fluid) would be beneficial in diagnosing Parkinson’s and monitoring its progression.

The team adapted a RT-QuIC protein misfolding assay — a new test that can help in the early detection of Parkinson's disease by identifying the formation of abnormal clumps of alpha-synuclein — to analyze samples biopsied from the salivary gland, or submandibular gland, for the presence of misfolded alpha-synuclein. The assay distinguished between Parkinson’s and healthy subjects with high diagnostic accuracy. To better validate RT-QuIC as a potential Parkinson’s biomarker tool, the investigators will test submandibular gland and cerebrospinal fluid (CSF) samples from subjects in the Systemic Synuclein Sampling Study (S4). The study aims to determine if and how alpha-synuclein can be used to diagnose Parkinson's, track its progression and evaluate the impact of therapies.

Hypothesis:
The team hypothesizes that the amount of misfolded alpha-synuclein detected in body fluids and peripheral tissue biopsies can serve as a diagnostic biomarker to distinguish people with Parkinson’s from those without and will correlate with the severity of disease progression.

Study Design:
This study will determine the clinical utility and compare the performance of the alpha-synuclein RT-QuIC assay via testing of submandibular gland biopsies and CSF samples from the well-designed S4 cohorts study. Cohorts consist of Parkinson’s patients with different alpha-synuclein fiber aggregate densities (n=18 early, 20 moderate, and 21 advanced) and people without Parkinson’s ( n=21). The team will initially subject a subset of three samples from each group for RT-QuIC standardization and optimization. They will then perform the RT-QuIC assay with all of the remaining samples and subjects from the S4 study.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
Detection of ultra-low levels of pathological alpha-synuclein in peripheral biopsies and body fluids would improve the early diagnosis of Parkinson’s and could also be used to monitor disease progression and the effectiveness of treatments.

Next Steps for Development:
If successful, the team would like to extend its alpha--synuclein RT-QuIC assay to other well-designed Parkinson’s cohorts to increase sample size. Its goal is to recommend this assay for clinical diagnosis of early Parkinson’s, allowing neurologists to consider early therapeutic intervention to slow down or delay the progression of the disease.


Researchers

  • Anumantha G. Kanthasamy, PhD

    Ames, IA United States


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