Parkinson's disease is the 14th leading cause of death in America, as reported by the Centers for Disease Control and Prevention. Nearly 1.5 million Americans live with Parkinson's disease, for which there is no cure. But what if a potential cure was hidden in an artificial sweetener?

Parkinson's disease is a neurodegenerative disorder where neurons stop communicating properly due to the buildup of a protein called α-synuclein. The α-synuclein is a protein that aggregates as part of Parkinson's disease development. It is not known what α-synuclein does normally, but its participation in Parkinson's is what makes it of interest. The buildup of the protein during disease onset breaks down cell signaling machinery between neurons in the brain. When messages cannot be relayed to other neurons, the brain's function begins to deteriorate. The neurons cannot send messages mostly in the forward direction, and the neuron dies as a result until all that is left is the α-synuclein aggregates and the cell body of the neurons. This "dying back" pattern of neurons, as described by Dr. Scott Brady, Ph.D.,and colleagues in a 2012 publication is what creates Parkinson's and leads its symptoms like tremors, speech changes, and impaired balance.

A new study, done by Drs. Ehud Gazit, Ph.D., and Daniel Segal, Ph.D., of Tel Aviv University's Department of Molecular Microbiology and Biotechnology and the Sagol School of Neuroscience respectively, indicates that the artificial sweetener, mannitol, can prevent α-synuclein molecules from sticking together in the first place. However, this prevention of the molecular level of Parkinson's disease still needed to be tested in real brains.

To test the capabilities of mannitol in the brain, the researchers used fruit flies carrying α-synuclein genes. To study fly movement, they used a "climbing assay," in which the ability of flies to climb the walls of a test tube indicates their locomotive capability and their affectation by Parkinson's disease. Initially, 72 percent of normal flies were able to climb up the test tube, compared to only 38 percent of Parkinson's affected flies. Researchers added mannitol to the food of the flies with the α-synuclein gene for 27 days and found that 70 percent of the flies could climb the walls of the test tube, indicating that the presence of mannitol rescued their brains from the degeneration that causes Parkinson's. Similarly, there were 70 percent fewer α-synuclein clumps in the brains of these flies fed the mannitol treatment, indicating that the mannitol is working on the level of α-synuclein protein and not anywhere else to create a coincidental effect on preventing Parkinson's.

The findings were promising in flies and were then reproduced in mouse brains in a second experiment. After four months of being injected with mannitol, mice showed a serious decrease in the levels of α-synuclein in the brain.

Mannitol appears to work very well in the two animal models mentioned above. This is likely because the molecule is small enough to cross the brain's blood/brain barrier. This barrier separates the blood stream from the brain's own circulation of extracellular fluid. It often prevents bodily diseases from infecting the brain. This is a very important mechanism, as it keeps the brain from being too negatively affected by drugs or sickness. However, some molecules can cross this barrier. The researchers have found that mannitol does indeed cross the blood brain barrier and suggest that it works on individual α-synuclein proteins to prevent them from sticking together and therefore prevent neurodegeneration.

While the results regarding mannitol and Parkinson's disease are promising, nothing has been established yet about doses and just how much will be safe for human ingestion. If tested in humans with positive results, mannitol could prove to be a potential cure for the incurable Parkinson's disease.

Source: Shaltiel-Karyo R, Frenkel-Pinter M, Rockenstein E, et al. A Blood-Brain Barrier (BBB) Disrupter Is Also a Potent α-Synuclein (α-syn) Aggregation Inhibitor: A Novel Dual Mechanism of Mannitol for The Treatment of Parkinson Disease (PD). The Journal of Biological Chemistry. 2013.