Study Rationale:
Some forms of early-onset Parkinson's disease are caused by dysfunction in the recycling of mitochondria, which are the powerhouses of our cells. Damaged mitochondria that need to be recycled are marked with a small protein named ubiquitin. This process does not happen in some early-onset patients, and the damaged mitochondria build up and can cause the cell to die.
Hypothesis:
Our hypothesis is that the absence of the ubiquitin marking of damaged mitochondria in white blood cells can be used to identify patients with faulty mitochondrial recycling.
Study Design:
This current study aims to test the detection of ubiquitin marking of damaged mitochondria in white blood cells from healthy people and early-onset patients with a known mitochondrial recycling fault to ascertain the reliability of the assay. Blood samples will be collected from early-onset Parkinson's patients and people without the disease. White blood cells will be isolated and treated with a toxin that damages their mitochondria. We will then determine if the damaged mitochondria are marked for recycling with ubiquitin. In white blood cells from patients with a fault in mitochondrial recycling, the mitochondria will not be marked with ubiquitin.
Impact on Diagnosis/Treatment of Parkinson's disease:
If we can detect the absence of ubiquitin marking of damaged mitochondria, we could identify patients with this mitochondrial dysfunction. These people could potentially test drugs designed to stimulate the recycling of damaged mitochondria, as they would be the most likely to benefit.
Next Steps for Development:
In future studies, we plan to test early-onset Parkinson's patients with an unknown disease cause to determine if they have a fault in the recycling of mitochondria.