Daniel Segal, PhD, and colleagues at Tel Aviv University investigated the effects of mannitol on the brain by feeding it to fruit flies with a form of PD that has highly aggregated α-synuclein.
The researchers used a "locomotion climbing assay" to study fly movement. Normal flies scamper right up the wall of a test tube, but flies whose brains are encumbered with α-synuclein aggregates stay at the bottom, presumably because they can't move normally. The percentage of flies that climb one centimeter in 18 seconds assesses the effect of mannitol.
An experimental run tested flies daily for 27 days. After that time, 72% of normal flies climbed up, in comparison to 38% of the PD flies. Their lack of ascension up the sides of the test tube indicated "severe motor dysfunction."
In contrast, were flies bred to harbor the human mutant α-synuclein gene, who as larvae feasted on mannitol that sweetened the medium at the bottoms of their vials. These flies fared much better -- 70% of them could climb after 27 days. And slices of their brains revealed a 70% decrease in accumulated misfolded protein compared to the brains of mutant flies raised on the regular medium lacking mannitol.
It's a long way from helping climbing-impaired flies to a new treatment for people, but the research suggests a possible novel therapeutic direction. Dr. Segal, however, cautioned that people with PD or similar movement disorders should not chew a ton of mannitol-sweetened gum or sweets; that will not help their current condition. The next step for researchers is to demonstrate a rescue effect in mice, similar to improved climbing by flies, in which a rolling drum ("rotarod") activity assesses mobility.
"Until and if mannitol is proven to be efficient for PD on its own, the more conservative and possibly more immediate use can be the conventional one, usin
|Contact: Phyllis Edelman|
Genetics Society of America