Study Rationale:
Alpha synuclein is a protein that accumulates inside neurons in Parkinson’s disease. A lot of research has assume,d but never fully prove,n that this protein can move from one neuron to the net, which would cause a spreading of the tissues affected. An alternative explanation for the spreading of the disease, is that other cells or factors in the body contribute to a ‘diseased’ environment which causes the alpha synuclein to independently accumulate in more neurons and tissues. In this study, we want to combine all of the available preclinical models to finally definitively determine if alpha synuclein really moves between neurons or if other factors are at play.
Hypothesis:
We think that alpha synuclein behaves differently in patients that in any models of Parkinson’s disease. We think that something in the body causes an upregulation of the amount of alpha synuclein in each neuron independently but synergistically so that once one neuron has accumulated too much, other neurons are more susceptible to accumulating it too.
Study Design:
We will transplant stem cells with different amounts of alpha synuclein into preclinical models that also express different amounts and forms of alpha synuclein protein. This will help us determine which aspects are important for spreading of the pathology. We will also change where these neurons are transplanted into the preclinical models to allow us to understand why some brain regions are affected in Parkinson’s disease while others aren’t.
Impact on Diagnosis/Treatment of Parkinson’s disease:
We think the current models of Parkinson’s disease are missing key aspects of the pathology in patients which is limiting the development of preventative treatments and future therapies. By answering one of the fundamental questions in the field, we can propel research in the right direction.
Next Steps for Development:
The results from our study will help guide how to look for Parkinson’s disease in patients before it appears and how to prevent it from spreading from one area to another. It will also have implications for how to better help patients who are receiving cell therapy, a procedure which is having a revival in current clinical trials.