Artificial sweetener against Parkinson's

Israeli researchers: mannitol inhibits the disease in BH

Parkinson's disease - tremor, in Hebrew - is a degenerative disease of the nervous system, which manifests itself in tremors and movement difficulties, and later in a decline in brain function to the point of insanity - dementia. The number of patients in the world is estimated at more than seven million (including boxer Muhammad Ali and actor Michael J. Fox), and in Israel there are at least 20,000 patients.

Pathologically, the cause of the symptoms of the disease is the death of brain cells that produce dopamine, after certain protein clumps are formed in them. A discovery by researchers from Tel Aviv University may pave the way for the development of a new treatment for the disease, using an artificial sweetener. The researchers looked for the substance that breaks down - in a test tube - the protein clumps, and discovered that the sugar alcohol, mannitol, does the job very efficiently. Later they tested the effect of the substance on fruit flies (Drosophila) in which the gene for human Parkinson's disease was implanted.

Transplanting the gene severely impairs the motor function of these flies (disrupting their ability to climb the walls of a test tube). The researchers discovered that the mannitol improved the motor function of the diseased flies by tens of percent, and their ability to climb. In the next step, the researchers moved to model mice - mice whose brains had been implanted with the gene for the production of the protein that causes the disease in the human brain. Even in these mice, an injection of mannitol resulted in a very significant decrease in the formation of the structures associated with Parkinson's disease. The research was led by a team of researchers from Tel Aviv University, led by Prof. Ehud Gazit, who is the chief scientist at the Ministry of Science and Technology, Prof. Danny Segal, Dr. Ronit Sheltiel Kario, research student Moran Frankel Pinter and Prof. Eliezer Masih from the University of California, San Diego. There the experiments were done on mice. The study was published in the journal Biological Chemistry.

long way

"The next step in the experiments will be to optimize," says Prof. Gazit. "To test the most effective dose, and to test similar substances - for example, additional polysaccharides - to see if their combination has a better effect on the protein clumps in the brains of the mice, in the hope that this will result in treatment of the disease."

The great advantage of mannitol is that the substance is already approved for a variety of medical uses, and can be given by injection, for example, to treat severe edema. It is also one of the only substances that is able to open the Blood Brain Barrier, the blood filter that prevents many substances from reaching the brain. "Today we understand much better the molecular mechanism of Parkinson's and other neurodegenerative diseases, says Gazit. "The process of developing a drug is very, very, very long - I don't know if it will take ten years or twenty - but we went through two important steps towards developing a drug: identifying the target site where the drug needs to act, and proving that modulation of that target site can affect the prognosis, At least in animal models."

As mentioned, the development of a drug may take many years, but the researchers are optimistic, partly because the mechanism of Parkinson's disease is somewhat similar to that of Alzheimer's and other neurodegenerative diseases of the nervous system. The success of the first experiments with mannitol, along with other developments in the field of treatment, prevention and delay of such diseases, give rise to hope that in a few decades we will be able to forget about dementia diseases, at least some of them.
The research article in the Journal of Biological Chemistry