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Funded Studies

Production of Preclinical Model of REM Sleep Behavior Disorder Using Alpha-synuclein Fibrils

Study Rationale: REM sleep behavior disorder (RBD) is characterized by abnormal motor behaviors during the REM phase of sleep and is highly predictive of Parkinson’s disease (PD). A brain region called the sublaterodorsal tegmental nucleus (SLD) is thought to play an important role in RBD and is known to develop Lewy bodies, a well-known hallmark of PD. In this study, we will assess whether pathology in the SLD leads to RBD in mice. The findings that could provide insights into the causes of RBD and how it leads to PD.

Hypothesis: We predict that a well-characterized animal model of RBD will enhance our understanding of prodromal (early) PD and provide insights into the relationship between RBD and PD.

Study Design: We will begin by injecting preformed alpha-synuclein fibrils, the abnormal form of alpha-synuclein protein found in people with PD, into the SLD of mice to determine whether the treatment will cause RBD and subsequent parkinsonism. Next, we will identify which SLD neurons are vulnerable to alpha-synuclein pathology and assess how this changes the functioning of the SLD. Finally, we will examine human brainstem autopsy samples to determine whether the same neurons identified in mice are affected in people with RBD.

Impact on Diagnosis/Treatment of Parkinson’s disease: A validated model of synucleinopathy-driven RBD will provide new insights into events that occur very early in PD and could yield new therapeutic strategies or targets. This RBD mouse model could also be used to evaluate treatments for the prodromal stage of PD, arguably the best time for therapeutic intervention.

Next Steps for Development: If successful, we anticipate researchers using this synucleinopathy-based RBD mouse model to validate various candidates or targets for modifying PD at a prodromal stage, thereby accelerating their path to clinical trials.


  • Kelvin C. Luk, PhD

    Philadelphia, PA United States

  • Hansoo Yoo, MD

    Philadephia, PA United States

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