Addressing the Potential of the Prion Hypothesis in Parkinson’s Disease
Yesterday, Michael J. Fox Foundation (MJFF) staffers Kuldip Dave, PhD, Brian Fiske, PhD, and Niketa Sheth attended a workshop co-sponsored by The Kinetics Foundation to address the potential of a budding hypothesis in the field of Parkinson’s disease (PD) research: That the alpha-synuclein protein implicated in PD might spread throughout the brain.
The hypothesis suggests that alpha-synuclein might act in a way that is similar to a prion, an infectious protein capable of transmitting disease from one organism to another. Prion diseases include bovine spongiform encephalopathy (BSE) (“mad cow”) disease, which is most commonly transmitted to humans when they eat food contaminated by the brain, spinal cord or digestive tract tissue of infected cattle.
In Parkinson’s, the hypothesis is different: that alpha-synuclein might move from cell to cell within the brain. Alpha-synuclein is not infectious, however, and there is absolutely no evidence that PD can spread from person to person.
So why could this idea be so important to people with Parkinson’s?
All people with PD experience clumping of alpha-synuclein in their brains. While there are still questions as to whether alpha-synuclein plays a direct causative role in PD, targeting this alpha-synuclein aggregation is of major interest to researchers aiming to develop a Parkinson’s disease-modifying drug. In the past, they worked to develop such therapies with the belief that the clumps of alpha-synuclein stayed in the cell. But if it’s true that alpha-synuclein spreads from cell to cell, scientists and drug developers alike might alter the way they think about targeting these clumps.
Yesterday's workshop was meant to address several questions: Is the prion hypothesis worth pursuing, and if so, what are some of the critical unknowns that science has yet to address? And moving forward, what might be the impact on therapeutic development?
Lately, there has been much buzz around the idea that alpha-synuclein might be a prion-like protein. A 2011 study from the University of Pennsylvania provided critical support for the hypothesis. Other researchers, including Patrik Brundin, MD, PhD, from Lund University in Sweden, are currently thinking about how to develop PD therapies to inhibit alpha-synuclein’s spread from cell to cell.
Stay tuned for updates in this space, as those in the field of PD research continue to zero in on the potential of the prion hypothesis.