AGING
July 2, 2013

A Promising New Parkinson's Treatment

A substance found in sugar-free gum helps prevent the build-up of the clumps of protein key to the disease.

Have you ever wondered what ingredient causes the sweet, sugary taste in many medicine tablets?

That ingredient is mannitol, a sugar alcohol derived from most fungi, bacteria, algae and plants. A common component of sugar-free gum and candy, mannitol has been approved by the FDA as a diuretic to remove excess fluids from medicines.

Mannitol also is used in cutting-edge neurosurgery techniques to create holes in the blood-brain barrier so other drugs, such as chemotherapies, can enter the brain.

Although mannitol is already approved for a variety of clinical interventions, more testing of the effectiveness and safety of mannitol is needed before it can be added to the list of alternative methods to combat Parkinson’s.

The candy-like substance may have another attribute: preventing a major symptom of Parkinson’s disease, according to researchers at the University of Tel Aviv in Israel.

Parkinson’s disease is the second most common neurodegenerative disorder, affecting 1 in 100 Americans over the age of 65. It causes deficits in motor control and nerve function primarily by affecting dopamine pathways in one of brain’s motor centers, the basal ganglia.

While many medications are approved for treating symptoms of Parkinson’s disease, none of them halts disease progression and there still is no cure.

Mannitol appears to prevent the buildup of clumps of a protein known as α-synuclein. Although the role of α-synuclein in the brain is not well understood, the gene for α-synuclein was identified as the first genetic risk factor for Parkinson’s disease in 1997.

The researchers screened a variety of compounds in an effort to find inhibitors that could prevent the development of α-synuclein clumps in brain. Out of the all the compounds tested, mannitol was among the most effective agents at blocking the formation of α-synuclein clumps in test tubes.

Next, the scientists tested mannitol in the brains of fruit flies genetically engineered to produce toxic α-synuclein clumps. The flies were run through a “climbing assay,” in which their motor performance was scored through their ability to climb the walls of a test tube. Only 38 percent of the genetically altered flies were able to climb the wall, demonstrating that they had motor problems similar to Parkinson’s disease.

But when the genetically altered fruit flies were fed mannitol, 70 percent of them could climb the test tube. The flies’ brains also showed a 70 percent reduction in α-synuclein protein aggregates compared to flies that had not been fed mannitol.

Similar results were found in a group of genetically engineered mice that also produced toxic α-synuclein clumps in brain. The scientists reported that mannitol produced a robust reduction in α-synuclein deposits in the brains of mice after four months of treatment.

Parkinson's patients should not try to treat themselves with mannitol however. Despite the successful results in the lab, Professor Daniel Segal of Tel Aviv University’s Department of Molecular Microbiology and Biotechnology cautions against the self-dosing by Parkinson’s patients.

Although mannitol is already approved for a variety of clinical interventions, more testing of the effectiveness and safety of mannitol is needed before it can be added to the list of alternative methods to combat Parkinson’s, such as eating red peppers and doing tai-chi.

For now, Dr. Segal recommends that doctors consider using mannitol in combination with other medications that have been approved for treatment of Parkinson’s but lack the ability to penetrate the blood-brain barrier. This is due to mannitol’s already proven ability to put holes in the barrier, allowing for the passageway of other beneficial compounds.

This study is published in the Journal of Biological Chemistry.

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