Israeli researchers have developed substances that protect cells from oxidative damage. In experiments on mice, these substances succeeded in weakening symptoms of multiple sclerosis and Parkinson's
Oxidation is generally not beneficial to materials. Iron that comes into prolonged contact with oxygen gets covered in rust, wine that is exposed to the air for a few days oxidizes and sours and the same happens to old milk.
A similar thing also happens in the human body. Oxidation processes occur in the body as part of the natural life mechanisms. Some of the products of these mechanisms are substances with strong and destructive oxidative potential called free radicals. The human body usually succeeds in breaking down the free radicals and preventing the heavy damage that may be caused by their accumulation, but at older ages the breakdown mechanisms do not work effectively and as a result the concentration of free radicals in the body increases. Thus begins a slow and constant process of oxidizing the cell components, which eventually leads to cell destruction. It is the constant destruction of cells that underlies aging, and many diseases, especially those that characterize old age, break out or are felt due to the destructive action of free radicals.
About ten years ago, the involvement of free radicals in neurodegenerative diseases such as Alzheimer's, Parkinson's and multiple sclerosis began to become clear. In all these diseases, it was found that the level of the body's defense systems that take care of the breakdown of free radicals decreases significantly, which leads to the accumulation of harmful substances in the brain. The high level of free radicals can explain some of the symptoms associated with neurodegenerative diseases. In multiple sclerosis, for example, there is a direct connection between the onset of the disease and the creation of free radicals and the activation of enzymes that break down the cell walls in the brain.
"Our assumption was that if we knew how to stop the activity of free radicals and prevent the activation of the enzymes that break down the cell walls, we could prevent the damage caused to the cells during the disease," says Prof. Dafna Atlas from the Institute of Life Sciences at the Hebrew University. Atlas therefore approached to design materials that would be able to carry out the task.
"The first requirement was to create substances capable of penetrating the brain. The brain is separated from the body by a partition called the blood-brain barrier - a system of membranes that prevent substances from entering the brain," explains Atlas. "When developing a treatment for nerve diseases, we first look for substances that manage to penetrate this barrier. Since the oxidation processes take place inside the cells, materials must be designed that can enter the cells and remain in them. These materials must also be non-toxic, since their use should be prolonged and daily."
Atlas decided to design materials that would be chemically close to natural materials and would be able to integrate into the system that protects the cells from the oxidative damage caused by free radicals. She prepared a series of several substances that all have in common a chemical group that exists in the natural substances that protect the cell from oxidative damage. This group binds copper, which is known to cause excessive formation of free radicals - and neutralizes it. All these materials can be produced in relatively simple processes.
In the next step, Dr. Daniel Ofen from the Felzenstein Institute at Tel Aviv University and Prof. Eldad Melamed from the Rabin Medical Center joined the research. The researchers added to the culture of cells special substances that produce free radicals and thus created environmental conditions saturated with oxygen, which cause the cells to die. In the next step, the new substances they developed were added to the cell culture and tested to see if they were able to break down the free radicals that were formed and thus affect the degree of survival of the cells. It turned out that the amount of free radicals formed in the culture decreased significantly after the addition of the antioxidants and most of the cells survived.
After the culture experiments, the researchers moved on to test the materials they developed in animals for the possibility of medical use, and this through the start-up company "Novia", which was established for the purpose. The first step was a toxicity test. "One of the substances tested was found to be completely non-toxic," says Atlas. "This encouraged us to start experiments on animals suffering from degenerative brain diseases similar to humans, which serve as a model for human diseases." The substance, named AD4, was tested in a special strain of mice that develop symptoms of a disease similar to the multiple sclerosis disease that attacks humans. After treatment with the substance, a marked improvement in the symptoms of the disease was discovered, accompanied by a decrease in the activity of the enzymes that break down the cell walls. The results of the research appear today in the journal "Journal of Neurochemistry".
Atlas adds that in a new research paper, which is in the process of publication, the research team found that AD4 also effectively reduces Parkinson's symptoms in mice. "The original idea, which was based on the assumption that lowering the level of free radicals would lead to relief in the symptoms of degenerative brain diseases, has proven itself, but it must be remembered that at this stage it is only animals and there is still a long way to prove the effectiveness of the AD4 treatment in humans."
