By Sarah Carnvek
Sweet news from Israel for Parkinson's disease (PD) sufferers: A Tel Aviv University research team has shown that the artificial sweetener mannitol may be a key in fighting this debilitating disease.
Take a closer look at a pack of sugar-free gum or candy and you'll see that mannitol, a sugar alcohol produced by fungi, bacteria and algae, is a common ingredient. The sweetener is also used in the medical field — it's approved by the US Food and Drug Administration (FDA) as a diuretic to flush out excess fluids, and used during surgery to open the blood/brain barrier to the passage of other drugs.
The mannitol molecule. Photo courtesy of Wikimedia Commons
Now, Professors Ehud Gazit and Daniel Segal of Tel Aviv University's Department of Molecular Microbiology and Biotechnology and the Sagol School of Neuroscience, along with their colleague Ronit Shaltiel-Karyo and PhD candidate Moran Frenkel-Pinter, have found that mannitol also prevents clumps of the protein α-synuclein from forming in the brain — a process that is characteristic of PD.
Although this is an exciting breakthrough, Segal warns against self-treatment or ingesting mannitol in large quantities simply based on these initial findings.
"People should not eat it as much as they want. This may be harmful. I would not recommend it to any human being, as we have no idea what the side effects would be," Segal says. "More testing must be done."
Seven million to 10 million people worldwide are living with PD, a disorder of the brain that leads to tremors, difficulty walking, and coordination problems. There is no known cure for this neurodegenerative condition, and scientists worldwide are seeking new treatments to control the symptoms.
The Tel Aviv University results were published in the Journal of Biological Chemistry and presented at the 2013 Drosophila Conference in Washington, DC; at the 2013 Alzheimer/Parkinson Disease Conference in Florence, Italy; and in the 2013 EUROCARB conference in Tel Aviv. Upon publication that mannitol could be a novel therapy for the treatment of Parkinson's and other neurodegenerative diseases, the research also gained headlines internationally.
Non-stick α-synuclein molecules
After identifying the structural characteristics that facilitate the development of clumps of α-synuclein, the researchers set out to find a compound that could inhibit the proteins' ability to bind together.
Segal says he and his fellow researchers looked at a variety of small molecules and found that “certain small sugars appeared to have a positive effect in preventing aggregation of the protein." Among them, they found mannitol – already FDA-approved for use in a variety of clinical interventions.
To test the capabilities of mannitol in the living brain, the researchers turned to transgenic fruit flies (Drosophila) engineered to express the human gene for α-synuclein. They used the "climbing assay" test, which measures the ability of flies to climb the walls of a test tube. In the initial experimental period, 72 percent of normal flies were able to climb up the tube, compared to only 38 percent of the genetically-altered flies.
The researchers then added mannitol to the food of the genetically altered flies for a period of 27 days and repeated the experiment. This time, 70 percent of the mutated flies could climb up the test tube. In addition, the researchers observed a 70 percent reduction in aggregates of α-synuclein in mutated flies that had been fed mannitol, compared to those that had not.
The scientists performed a second study measuring the impact of mannitol on mice engineered to produce human α-synuclein, developed by Eliezer Masliah of the University of San Diego. After four months, the mice injected with mannitol also showed a dramatic reduction of α-synuclein in the brain.
The research was funded by a grant from the Parkinson's Disease Foundation and supported in part by the Lord Alliance Family Trust. Now, Segal and his cohorts would like funds to further their studies, re-examine the structure of mannitol and introduce modifications to optimize its effectiveness.
For now, he suggests that doctors could use mannitol in combination with other medications that have been developed to treat PD but which have proven ineffective in breaking through the blood/brain barrier. These medications may be able to "piggyback" on mannitol's ability to open this barrier into the brain, he explains.
"I don't know [whether mannitol will provide] a cure; this may be too optimistic. If we can slow down the disease, diagnose it early enough and reduce the amount of suffering, I will be more than happy," sums up Segal. "I'm definitely hopeful."