Gene therapy against opiate addiction
Millions of people are injected with morphine and other opiates to relieve severe pain in malignant diseases, surgical interventions, nerve damage and other conditions. However, the sensitivity of the body to morphine gradually decreases, which requires an increase in the administered doses and increases the patient's chances of forming dependence.
Natural anesthetics produced by the body, such as endorphins (endogenous morphines), relieve pain by binding to receptors on the surface of neurons. The entry of these compounds into the cell is regulated by alternating phases of receptor activity/inactivity.
The natural cycles of activity of endorphin receptors are caused by their migration from the cell surface into the cell through endocytosis (retraction of a portion of the membrane with a receptor into the cell and the formation of membrane vesicles).
The effect of opiates disrupts this mechanism, which leads to the development and gradual strengthening of the tolerance of the nervous system to the drug and aggravation of the drug dependence of the patient on morphine.
In experiments on mice, scientists at the University of California (San Francisco), working under the guidance of Dr. Jennifer Whistler, demonstrated the possibility of using a genetically engineered approach to solve this problem.
The authors suggested that the side effects of morphine are due to the loss of the ability of receptors to immerse themselves in the cytoplasm of the cell. To obtain evidence for the hypothesis, they created genetically modified mice, the only difference between which and normal animals was that their endorphin receptors, after meeting with opiates, could enter into endocytosis in the same way as it happens in the presence of endorphins. For these animals, morphine continued to be an excellent analgesic, not causing the development of tolerance and dependence.
Currently, several methods of combating morphine addiction are at various stages of testing, including the use of morphine derivatives such as oxycontin, which have an effect on the principle of delayed release, or only after digestion in the gastrointestinal tract. Other approaches are aimed at developing morphine derivatives that selectively act on certain subtypes of opioid receptors.
The authors believe that the results they obtained will give rise to a new direction of work and will lead to the emergence of effective analgesics that do not cause either dependence or a decrease in effectiveness due to the development of tolerance.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily.
04.02.2008