Gene therapy shows promise in the treatment of multiple sclerosis
A huge number of "superheroes" work in the human body: antibodies that destroy infectious agents, cells that ensure tissue regeneration, and structures that ensure the smooth functioning of body systems. One of these structures is myelin, a material that forms a protective insulating shell around the long processes of nerve cells – axons. The integrity of this shell ensures the speed and efficiency of transmission of nerve impulses. However, myelin and the specialized cells that form it, oligodendrocytes, are damaged in demyelinating diseases, such as multiple sclerosis. The result of this is a violation of the interaction between the damaged neurons.
Currently, the treatment of multiple sclerosis consists in modulating or suppressing immune responses, since the inflammation caused by them is considered to be the cause of death of oligodendrocytes and subsequent damage to neurons. Such therapeutic approaches reduce the frequency of relapses of the disease, but they do not have a significant effect on the progression of the disease in the long term.
Researchers at the California Institute of Technology, working under the leadership of Professor Paul Patterson, have found a way to help the brain replace damaged oligodendrocytes and myelin.
The method of gene therapy developed by them stimulates the differentiation of stem cells and progenitor cells in the brain tissue into oligodendrocytes by increasing the production of the leukemia inhibitory factor LIF protein. The results of earlier work on mouse models showed that this protein, naturally synthesized in the body, promotes self-renewal of nerve stem cells and suppresses myelin-destroying immune responses.
Gene therapy stimulates the formation of myelin-producing oligodendrocytes (green).
According to Professor Patterson, the uniqueness of the work lies in the fact that the local introduction of gene therapy vectors ensured the synthesis of therapeutic protein, and, accordingly, the restoration of myelin only in brain tissues. He also notes that such an approach avoids possible side effects associated with the introduction of a gene therapy drug into the bloodstream.
In a mouse model, the described method stimulated the proliferation of progenitor cells and their differentiation into mature oligodendrocytes synthesizing myelin. At the same time, the number of mature oligodendrocytes after therapy reached the indicators characteristic of healthy animals.
Currently, researchers are working on improving viral vectors – carriers of the therapeutic gene. Their goal is to create a vector that would ensure the production of a leukemia inhibiting factor exclusively in target cells and allow regulating the activity of this synthesis from the outside. They hope that, after conducting additional animal studies, the method they have developed can be tested in clinical trials.
The article by B. E. Deverman, P. H. Patterson Exogenous Leukemia Inhibitory Factor Stimulates Oligodendrocyte Progenitor Cell Proliferation and Enhances Hippocampal Remyelination is published in the Journal of Neuroscience.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the California Institute of Technology:
Caltech Researchers Develop Gene Therapy to Boost Brain Repair for Demyelinating Diseases.
15.02.2012