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Maximizing the Sensitivity of Seed Amplification Assays Used to Detect Alpha-synuclein Aggregates

Study Rationale: One characteristic of Parkinson’s disease (PD) is the aggregation of proteins such as alpha-synuclein in the brain. To diagnose PD, it is important to be able to detect such aggregates in more easily obtained tissue samples, such as blood. This detection is enabled by a clever process that involves amplifying the aggregates in these samples. In maximizing the sensitivity of these assays, we need to ensure that the test conditions do not allow aggregates to form spontaneously, which would lead to false positive diagnoses. Our aim is to develop a diagnostic method that eliminates the spontaneous formation of aggregates.

Hypothesis: Our hypothesis is that if the amplification reaction is carried out in tiny water droplets, we can eliminate the spontaneous formation of aggregates and run hundreds of experiments at the same time, obtaining results that are highly reproducible

Study Design: We will improve on the best currently available diagnostic methods for detecting protein aggregates by miniaturizing the assay and eliminating the main source of false positives: the spontaneous formation of new aggregates under the test conditions. Furthermore, we will try to identify new substrates for the assay that will allow us to discriminate between the similar but distinguishable protein aggregates involved in PD and multiple systems atrophy (MSA).

Impact on Diagnosis/Treatment of Parkinson’s disease: A noninvasive test that would distinguish between PD and MSA would facilitate early detection and monitoring of disease progression, as well as more targeted treatment for individuals with these disorders.  

Next Steps for Development: This project is a joint venture between an academic university research group and a pharmaceutical company. The participation of a large company from the start will enable a rapid development of the assay into a clinically useful method, if the present project proves to be successful.


Researchers

  • Alexander Kai Buell, PhD

    Lyngby Denmark


  • Kaare Bjerregaard-Andersen, PhD

    2500 Valby Denmark


  • Pekka Kallunki, PhD

    Copenhagen Denmark


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