Funded Studies
Study Rationale:
People with a form of idiopathic REM sleep behavior disorder (iRBD) experience nightmares and lash out physically during a stage of sleep when the body's muscles are normally relaxed. Most of these individuals develop Parkinson’s disease (PD) a few years after this disorder first appears. Therefore, iRBD represents an early stage of PD that offers a unique opportunity for identifying the cellular changes that underlie the neuronal damage associated with the disease. Neurons depend on energy provided by mitochondria, a subcellular structure that contains its own DNA. Defects in mitochondrial DNA can cause a failure in energy production, which initiates neurodegeneration — a process that can lead to irreversible neuronal damage.
Hypothesis:
We hypothesize that alterations in mitochondrial DNA bring about neurodegeneration early in PD. In this study, we seek to establish whether changes in the content or integrity of mitochondrial DNA precede — or are already present at — the earliest stages of the disease.
Study Design:
We plan to measure the amount of mitochondrial DNA present in each cell — and the proportion of that DNA contains large deletions — in people with iRBD, late-stage PD, and in control volunteers. These measurements will allow us to assess whether mitochondrial DNA damage precedes, or is a consequence of, Parkinson’s disease.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
The proposed studies will provide crucial information for evaluating whether changes in mitochondrial DNA content and integrity are biomarkers for the early diagnosis or progression of Parkinson’s disease.
Next Steps for Development:
The next steps will be to investigate whether measurement of mitochondrial DNA content and integrity serves to monitor the therapeutic effect of disease-modifying drug treatments at the early stage of PD in clinical trials.