Study Rationale: Mitochondria are small capsules inside cells that generate energy. There are lots of mitochondria in brain cells because the brain uses a lot of energy. Researchers have found that mitochondria can work less efficiently as people get older and that their damage could contribute to Parkinson’s disease. Each mitochondrion contains a small genome and we think that damage to the DNA of this genome could be a sign of Parkinson’s disease. Pieces of mitochondrial DNA can be found outside of cells, circulating in body fluids so we want to use this as a window to observe mitochondrial changes in functional people.
Hypothesis: We think there is more damaged mitochondrial DNA shipped out of brain cells in Parkinson’s disease, so we want to look at this in the body fluids of patients and understand the way that brain cells deal with damaged mitochondrial DNA by researching the process using brain cells in vitro (in a dish and under a microscope).
Study Design:
We will take body fluid samples collected from healthy people and those with Parkinson’s disease, isolate small vesicles coming from cells and purify the mitochondrial DNA that is inside. We will then measure how many mitochondrial genomes there are and how much of the DNA is damaged. We want to tie this with other information from patients. We will also look at neurons in vitro to see what type of DNA is packaged in the vesicles and if this influences other cells. We would also like to know more about whether vesicles coming from the brain exist in the blood and what they contain.
Impact on Diagnosis/Treatment of Parkinson’s disease:
This study could help provide a biomarker that could mean earlier diagnosis and treatment. This study might make testing patients a much easier process and could help reduce the need for a spinal tap in certain situations.
Next Steps for Development:The next steps toward clinical application are better and earlier diagnosis and treatment. If successful, clinical trials could be made to offer treatments tailored to those patients that might have an underlying cause related to mitochondrial deregulation.