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A molecule that may enable the diagnosis and development of advanced and effective drugs for the treatment of depression, anxiety, and other mental disorders

Mood disorders, such as depression, are very common and, according to the World Health Organization, affect the health of at least a tenth of the world's population. Scientists in different parts of the world have invested a lot of effort in trying to understand the phenomenon, but the molecular mechanisms and cells that lie at the root of these disorders have, so far, only been partially understood.

depression. Illustration: shutterstock
depression. Illustration: shutterstock

Mood disorders, such as depression, are very common and, according to the World Health Organization, affect the health of at least a tenth of the world's population. Scientists in different parts of the world have invested a lot of effort in trying to understand the phenomenon, but the molecular mechanisms and cells that lie at the root of these disorders have, so far, only been partially understood.
The effectiveness of the existing drugs for the treatment of depression is not sufficient. In fact, 60-70 percent of patients do not recover as a result of treatment with these drugs, and the remaining 30-40 percent of patients report partial relief - and this only after a considerable period of time of using the drug. Many patients who take these drugs even suffer from various side effects. This state of affairs clearly shows a need for the development of new and improved drugs for the treatment of these disorders, and for this a better understanding of the causes and processes that cause the disease of the mood disorders is necessary.

Prof. Alon Chen and Dr. Orna Isler from the Weizmann Institute of Science, recently studied the molecular mechanisms of the serotonin system in the brain (improper regulation of this system is related to depression and anxiety). Prof. Chen and his research partners examined the role of microRNA molecules (small genetic molecules that play a role in controlling cellular processes that do not carry information to build proteins), in regulating the activity of serotonin-producing nerve cells. They were able, for the first time, to determine the unique "fingerprint" of the microRNA molecules of these serotonin-producing nerve cells. Using bioinformatics techniques, which were later verified in the experiment, the scientists identified a connection between a certain microRNA, number 135, and two proteins that play key roles in regulating serotonin production and activity in nerve cells. The research findings are published today (Thursday) in the scientific journal Neuron.

The scientists noticed that the levels of the RNA segment (microRNA 135), in the serotonin-producing cells were increased after taking antidepressants. Mice genetically engineered to produce more microRNA 135 showed resistance to chronic stress and did not develop anxiety-like and depressive-like behaviors as expected. Accordingly, mice engineered to express low levels of microRNA 135 exhibited high levels of anxiety-like behavior and responded less to the administration of antidepressants. These findings show that an appropriate level of microRNA 135 in the brain is essential for a normal response to stress, the control of anxiety and depression, and an effective response to antidepressants. In the tests performed on humans suffering from depression, it was found that the level of microRNA 135 in their blood was extremely low. In addition, low levels of this molecule were found in the brains of suicidal people. It also turns out that the three genes involved in the creation of microRNA 135 are located in genetic regions that have been linked to an increased chance of suffering from bipolar mood disorder (manic depression).

These findings point to microRNA 135 as a potential advanced drug for depression, anxiety and other disorders, as well as a "target area" to which advanced drugs that will be developed in the future can be directed. It also turns out that changes in microRNA 135 levels in the blood can be used to test for depression and response to treatment. The company "Yeda Research and Development Ltd.", which promotes industrial and medical applications based on the inventions of Weizmann Institute of Science scientists, registered a patent for these findings, and recently granted the company "miCure Therapeutics" a license to develop a drug and a diagnostic method based on them. After completing another study in animals, the company hopes to start a clinical study in which an experimental drug and diagnostic method intended for humans will be tested.

Prof. Alon Chen heads a laboratory for experimental neuropsychiatry and behavioral neurogenetics, which is shared with the Weizmann Institute of Science and Max Planck Institutes from Germany.

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