Alpha-synuclein: that sticky protein that clumps in the brain cells of people with Parkinson's. Scientists think that aggregates of alpha-synuclein -- called Lewy bodies -- are toxic, killing off cells and leading to PD symptoms. Therefore, avoiding or breaking up Lewy bodies is a major focus of research.
The Michael J. Fox Foundation funds a robust portfolio of projects that target alpha-synuclein, and we're leading efforts to understand more about this protein, why it clumps together in the first place and how new cells are "infected" with Lewy bodies.
The projects we support that target alpha-synuclein to stop or prevent Parkinson's disease take one of four approaches:
- Lower alpha-synuclein levels overall: Scientists hypothesize that less alpha-synuclein means less opportunity for Lewy bodies, so they are exploring ways to prevent the body from making this protein, such as interfering with gene signaling. Complicating this approach is that we don't yet know the normal function of alpha-synuclein, and thereby the effect of wiping it out. However, pre-clinical models without alpha-synuclein appear to function normally, which is promising.
- Read more about a project that took this approach.
- Break up Lewy bodies in the cells: Since clumps of alpha-synuclein clog up cells, researchers are working on a therapy that would break up Lewy bodies (like untying a knot) and allow the cells to function properly.
- Learn about a project that's using this method.
- Help the cells clear out Lewy bodies: A cell may stay healthy if it is able to rid itself of the Lewy bodies before they have harmful effects. Scientists are working on therapies to either directly degrade Lewy bodies or to bolster the cells' cleaning mechanisms to flush out the alpha-synuclein clumps.
- Read more about one target in this category.
- Catch Lewy bodies on the move: One theory proposes that Lewy bodies are released from cells and infiltrate others to spread the disease. Another suggests that the diseased cells give off a signal to other cells that makes the alpha-synuclein in those secondary cells start to clump. Either way, if a drug could stop the disease from spreading between cells, it would stop its progression.
- Learn about a clinical trial of an antibody against Lewy bodies.
"We take a varied approach because we don't want to put all our eggs in one basket," said Kuldip Dave, PhD, who directs the MJFF alpha-synuclein portfolio. "We're after a drug that can stop or slow the progression of Parkinson's, and alpha-synuclein is a primary target. More approaches to treat the disease give us more chances of success."
Watch a webinar on this topic to learn more.