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- Prescription medication: a way has been found to speed up recovery from spinal cord injuries
Prescription medication: a way has been found to speed up recovery from spinal cord injuries
Russian scientists have found a method that opens the way to the creation of fundamentally new drugs for the treatment of severe spinal cord injuries. Researchers have found that disabling one of the genes responsible for balance and anxiety accelerates the recovery of motor functions. The hypothesis was tested on mice in which a common injury in humans was modeled. In the future, based on the found target, drugs can be created that will help patients return to a full life faster. For more information about innovative gene therapy— see the Izvestia article.
How spinal cord injuries are treated
Scientists from Sirius University of Science and Technology, together with colleagues from St. Petersburg State University and the Pavlov Institute of Physiology of the Russian Academy of Sciences, have discovered that disabling the TAAR5 receptor gene accelerates the recovery of motor functions after spinal cord injury. It is a protein that is activated by so-called trace amines, substances related to dopamine and serotonin. It was previously known that TAAR5 affects motor coordination and anxiety, but its role in recovery has been studied for the first time.
Spinal cord injury is severe damage to the nervous system, which often leads to permanent loss of motor functions. Existing treatment methods are mainly aimed at maintaining vital functions and combating complications, but not at regenerating the nervous tissue of affected people. The development of new molecular targets capable of stimulating recovery remains one of the main tasks of neuroscience.
In the experiment, mice of two lines were compared: normal and mutant, with the artificially disabled TAAR5 gene. Experts simulated spinal cord injury in animals, which mimicked the type of injury often found in humans. Within five weeks after surgery, they assessed the recovery of the grasping reflex, mobility of the joints of the hind limbs, as well as general motor activity and anxiety levels.
The results showed that mice with TAAR5 disabled recovered faster. Earlier, they regained the ability to grasp the support with their paws and better resumed joint mobility. At the same time, the differences between the groups were insignificant for complex motor tests requiring fine coordination.
— There is accumulating evidence that TAAR5 is involved in the regulation of many physiological processes, including neurogenesis. The potential of the central nervous system decreases with age, but our study in middle—aged mice showed that the absence of this protein has a positive effect on functional recovery, despite a decrease in regenerative capabilities," Daria Kalinina, senior researcher at the Neurobiology department at the Scientific Center for Genetics and Life Sciences at Sirius University, told Izvestia.
Scientists believe that the positive effect of their proposed approach is associated with increased levels of dopamine in certain brain structures in mice with TAAR5 disabled. Dopamine is known for its ability to stimulate neuroplasticity and protect nerve cells from death. In addition, suppression of the receptor may be able to reduce the inflammatory processes that develop in the spinal cord after injury and prevent its regeneration.
In addition, spinal cord injury caused increased anxiety in both groups of animals. However, in mice with TAAR5 disabled, the initial level of anxiety before injury was lower, which corresponds to previously published data on the anti-anxiety effect of turning off this gene.
— Apparently, this receptor restricts neuroplasticity and regeneration in the damaged spinal cord. We suggest that TAAR5 inhibition can be considered as a promising direction for the development of therapeutic strategies aimed at improving functional outcomes after spinal cord injury," said Daria Kalinina.
A new method of spinal cord injury treatment
In the future, based on the found target, drugs can be created that will help patients recover motor functions faster and return to a full life. In the near future, we also plan to study the molecular mechanisms underlying the observed effect and search for small molecules capable of selectively blocking the activity of the TAAR5 gene.
Most experimental studies involve the same molecular cascades, and these pathways have either already reached a clinical dead end or have shown a very modest effect, so looking at the TAAR5 trace amine receptor is a fresh approach, NTI expert on neurotechnology Svetlana Lebedeva told Izvestia.
— An attempt to avoid direct, crude intervention in the area of damage and instead subtly modulate the neurotransmitter balance, in particular dopamine, looks methodologically sound. It is able to dampen microglial inflammation. The fact that the effect was observed in animals with reduced regenerative potential slightly brings the model closer to real clinical practice, where the majority of patients with spinal injury are adults. The reduction of anxiety in mice with the disabled gene should not be discounted, this is a clinically significant bonus, because a patient who has not fallen into severe depression is objectively better at rehabilitation," the specialist said.
However, according to her, the critical limitations of this model are still much greater. Now we are talking only about the early stage of research conducted on mice with genetically disabled TAAR5, said Albert Rizvanov, head of the Center for Excellence "Personalized Medicine" at Kazan (Volga Region) Federal University. In such animals, recovery from spinal cord injury was indeed faster, but transferring these results to humans is not yet possible. He stressed that it is necessary to understand the systemic effects of suppressing this receptor: if it has been preserved in evolution, it probably performs some functions and its blockade can have not only advantages, but also side effects.
— The most promising scenario is not to "turn off the gene forever", but to create a drug that temporarily and selectively suppresses the activity of TAAR5, for example, in the period after injury, when it is necessary to enhance neuroplasticity and recovery processes, — said the specialist.
According to him, in theory, this target can be studied for other injuries of the central nervous system. First of all, these are spinal cord injuries, then potentially stroke and traumatic brain injury.
— Neurodegenerative diseases can also be considered as a research area, but there the path to practical application will be much longer and less predictable, — Albert Rizvanov noted.
The results are published in the international journal Biomedicines. The research is carried out within the framework of the state program of scientific and technological development of the federal territory "Sirius". The project received parity funding from the administration of the federal Territory and the Russian Science Foundation.
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