Study Rationale:
Dysfunction of mitochondria -- powerhouses of the cell -- is one of the possible causes of Parkinson's disease (PD). To supply all parts of the nerve cell with energy, mitochondria must be able to move down the axon, the cell's long and thin process. This movement can be compromised if mitochondria are damaged or if clumps of proteins get in their way. The inability of mitochondria to move down axons have been reported in PD and other neurodegenerative diseases.
Hypothesis:
We aim to determine whether deficit in mitochondrial movement takes place in human nerve cells derived from stem cells donated by people with PD and whether this deficit occurs in all forms of Parkinson's or only in some, i.e., in carriers of certain genetic changes linked to PD.
Study Design:
We have developed an automated technique that allows us to track the movement of 40,000 mitochondria at a time. Using this technique, we can detect even subtle changes in the number of moving mitochondria and the distance they move within the processes of nerve cells in vitro. From a repository of human induced pluripotent stem cells, which can become any type of human cell, we will select the cells tracing their origin to people with Parkinson's without a clear genetic risk factor and to those with one of the major genetic risk factors for Parkinson's disease. These stem cells will be prompted to become nerve cells, and the mitochondrial movement in each of these cell types will be evaluated.
Impact on Diagnosis/Treatment of Parkinson's Disease:
If deficit in mitochondrial movement is detected in nerve cells originating from people with PD, it can be used as a biomarker -- objective measure of disease -- in evaluating disease progression and new therapeutic approaches.
Next Steps for Development:
As new therapeutic strategies are developed, their effectiveness in restoring mitochondrial movement can be tested in vitro using our technique. In addition, searching for drugs that improve mitochondrial movement can help discover novel therapeutic targets and approaches.