Some inherited forms of Parkinson's disease (PD) are caused by mutations (genetic changes) that lead to the breakdown of mitochondria, cell's energy generators. In some cases of sporadic PD -- disease that is not inherited -- mitochondrial breakdown might still be an underlying cause. Little is known about these cases because mutations have been the primary focus of research so far. Also, properly identifying the cause of sporadic PD has not been possible. We aim to identify people with Parkinson's who do not have a known mutation affecting mitochondria but have dysfunctional mitochondria nevertheless. This population is more likely to benefit from therapies targeting mitochondria.
We hypothesize that signs (markers) of mitochondrial breakdown present in some inherited forms of PD will also be present in a sub-group of people with sporadic PD. We believe that the properties -- mass and length -- of mitochondrial DNA is a stable, robust and informative marker of mitochondrial breakdown. We will use appropriate controls to account for the normal variation in mitochondrial mass and length between individuals.
We will collect a small amount of blood from at least 50 people with sporadic PD, 50 healthy people and at least 15 people with inherited PD who have mutations in genes that regulate the production of mitochondria-related proteins. We will extract mitochondrial and nuclear DNA from a fraction of blood cells called mononuclear cells to assess mitochondrial breakdown. We will use this data to look for similarities between the groups of study participants. We can also store these samples and use them again later to confirm our findings.
Impact on Diagnosis/Treatment of Parkinson's disease:
This data will allow us to identify people with sporadic Parkinson's possibly caused by underlying mitochondrial breakdown. This will help clinicians to better organize ongoing trials of treatments targeting mitochondrial health. This data will also inform researchers of the contribution of mitochondrial breakdown to the overall cause of sporadic PD, allowing them to conduct a more focused search for new or improved therapeutic targets.
Next Steps for Development:
If our study is successful, sub-groups of people with sporadic Parkinson's could be invited to participate in clinical trials where approved compounds already known to improve mitochondrial health could be used, for example, certain antioxidants or compounds promoting mitochondrial renewal. Furthermore, the protocol for assessing mitochondrial breakdown could be used in larger patient cohorts and in cohorts at other clinics. In this case, mitochondrial breakdown would play a role of a standardized biomarker, i.e., an objective measure of disease. Finally, the identification of people with sporadic PD with likely mitochondrial breakdown via blood sample analysis could allow researchers to perform more in-depth studies using other techniques and/or cell types.