Does Mitochondrial Dysfunction in the Skin Predict That in the Brain?
Research Grant, 2018
Mitochondria -- the power generators of the cell -- do not function properly in Parkinson's disease (PD). This dysfunction, however, is not always present and can vary in its severity. We and other researchers found mitochondrial dysfunction outside of the brain, in the skin of people with PD, but it is not clear whether mitochondrial dysfunction in the skin reflects mitochondrial dysfunction in the brain. A modern brain imaging technique, 31P-Magnetic Resonance Spectroscopy (31P-MRS), allows an indirect measurement of mitochondrial function in the brain.
We will determine whether mitochondrial dysfunction outside of the brain, in the skin, reflects mitochondrial dysfunction inside the brain.
We will recruit both people with PD and healthy volunteers into this study. Study participants will donate skin samples via skin biopsy and the skin cells called fibroblasts will be grown from the samples in vitro. This will allow us to assess mitochondrial function and shape outside of the brain. At the same time, we will assess the mitochondrial function in the brains of study participants using 31P-MRS. This will allow us to determine whether people with PD who have mitochondrial dysfunction in their skin cells also have mitochondrial dysfunction in their brain.
Impact on Diagnosis/Treatment of Parkinson's disease:
Our project will allow us to identify individuals with Parkinson's who are most likely to benefit from a mitochondria-targeting drug. These drugs are most likely to work in the patients with particularly marked mitochondrial dysfunction. This approach -- matching people with certain disease features to a therapy most likely to help -- is known as personalized medicine.
Next Steps for Development:
In the future, we will test drugs in peripheral tissues, such as skin, of individuals with PD before starting disease-modifying treatment. We expect this approach to be much more powerful than treating all patients with the same drug and hoping that it will work equally well for everybody.
Professor of Movement Disorders Neurology at Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, UK
Location: Sheffield, South Yor, United Kingdom