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Maximizing Sensitivity of Alpha-synuclein Seed Amplification Assays by Eliminating Spontaneous Aggregation

Study Rationale: A key characteristic of Parkinson’s disease (PD) is the formation of alpha-synuclein aggregates in the brain. The ability to detect these aggregates in body fluids is important for diagnosis. Such detection is aided by an amplification reaction that makes alpha-synuclein aggregates easier to measure. To push the sensitivity of our assay to the highest possible level, we must make sure that these aggregates do not form spontaneously during the testing protocol, which would lead to false positive diagnoses. Our aim is to develop a diagnostic method that eliminates the spontaneous formation of alpha-synuclein aggregates.

Hypothesis: We hypothesize that if we carry out the amplification reaction in tiny water droplets, containing only a billionth of a liter of fluid, we can reproducibly run hundreds of experiments at the same time while eliminating the spontaneous formation of new aggregates entirely.

Study Design: We will improve on the best currently available diagnostic assays for detecting protein aggregates by miniaturizing the assay and eliminating the source of false positives — the formation of new aggregates under the assay conditions. In addition, we will attempt to identify new substrates for the assay that will allow us to discriminate between two diseases that are caused by protein aggregates of a similar, but distinguishable type: PD and multiple systems atrophy (MSA).

Impact on Diagnosis/Treatment of Parkinson’s disease: The ability to distinguish between PD and MSA in an early and non-invasive manner, and to track disease progression more closely, will be of great benefit for individuals with these disorders. Such an assay will facilitate a more effective targeting and monitoring of treatments.

Next Steps for Development: This project is a joint venture between an academic university research group and a pharmaceutical company. If the project is successful, participation of a large company from the outset will facilitate the rapid development of our assay into a clinically useful method.


Researchers

  • Alexander Kai Buell, PhD

    Lyngby Denmark


  • Kaare Bjerregaard-Andersen, PhD

    2500 Valby Denmark


  • Pekka Kallunki, PhD

    Copenhagen Denmark


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