Mary Poppins may not be medically trained, but she was right about at least one thing: a spoonful of sugar really does help the medicine go down. Mannitol is a sugar alcohol used commercially as an artificial sweetener and medically to facilitate the delivery of drugs into the brain by disrupting the blood–brain barrier. Now, scientists at Tel Aviv University (Israel) and University of California San Diego report that it also disrupts the aggregation of the protein α-synuclein in the brain, a process characteristic of Parkinson's disease. The discovery may lead to new therapies for Parkinson's and other neurodegenerative diseases.

After identifying mannitol as an effective compound for inhibiting α-synuclein aggregation in vitro, the team, led by Daniel Segal and Ehud Gazit, tested it in transgenic fruit flies expressing human α-synuclein, which model certain aspects of Parkinson's disease in humans, including α-synuclein aggregation and behavioral deficits. Only 38% of the transgenic flies succeeded in a locomotor assay compared with 72% of normal flies. But when transgenic flies were fed mannitol for 27 days, their locomotor assay success rate improved to 70%; furthermore, the amount of aggregated α-synuclein in their brains dropped by ∼70% (J. Biol. Chem. 288, 17579–17588; 2013).

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The research group next evaluated the effects of mannitol in transgenic mice overexpressing human α-synuclein, a rodent model of Parkinson's disease. Transgenic mice that received intraperitoneal injections of mannitol over a 4-month period had smaller amounts of aggregated α-synuclein in certain areas of the brain and less aggregated α-synuclein overall. No adverse effects of mannitol administration were observed in fruit flies or in mice.

The researchers found that although mannitol administration prevented α-synuclein aggregation in vitro and in flies and mice, it did not reverse aggregation in vitro or in transgenic mice.

More studies are needed to further assess the efficacy of mannitol as a treatment for Parkinson's disease, particularly in animal models that more closely recapitulate the development of the disease in humans. But the researchers believe that mannitol may be especially effective when used in conjunction with other medications that have been developed to treat Parkinson's disease but are hindered by the blood–brain barrier. Segal believes that such compounds may be able to “piggyback” on mannitol to cross that barrier, according to a news release from American Friends of Tel Aviv University.