Gene therapy of multiple sclerosis
In experiments on a mouse model of multiple sclerosis, researchers at the University of Florida, working under the guidance of associate Professor Brad E. Hoffman, demonstrated the possibility of suppressing or reversing the progress of the disease using a new method of gene therapy.
Multiple sclerosis is the most common neurological disease of young age, which affects about 2.3 million people worldwide. With this currently incurable disease, a person's own immune system destroys the myelin sheath around nerve fibers, which disrupts the transmission of nerve impulses. As a result, a person suffers from muscle weakness, visual impairments, speech and coordination.
In their work, the researchers used a harmless viral vector based on an adeno–associated virus to deliver a gene encoding a protein – myelin oligodendrocyte glycoprotein - to the liver of a mouse model of multiple sclerosis. Earlier studies have demonstrated the ability of this protein to effectively prevent and reverse the development of muscular dystrophy.
The introduction of a gene encoding this protein into liver cells stimulated the production of regulatory T-lymphocytes, specifically suppressing the immune attack on myelin. In a group of five animals, gene therapy prevented the development of experimental autoimmune encephalomyelitis – the mouse equivalent of multiple sclerosis. In another experiment, 8 days after a single administration of a gene therapy drug, all but one of the mice had a significant improvement in clinical symptoms of the disease.
The authors also note the long-term effect of therapy. Seven months after the prophylactic administration of the viral vector, no manifestations of the disease were registered in mouse models, whereas in untreated animals of the control group, neurological problems appeared after 14 days.
The combination of gene therapy with rapamycin, a drug used to apply stents to the surface and prevent rejection of donor transplants, has further increased its effectiveness. Rapamycin was chosen due to its ability to stimulate the proliferation of beneficial regulatory T-lymphocytes, while simultaneously suppressing the activity of undesirable in this case effector T-cells.
Among mice with late and terminal stages of the disease who received a combination of gene therapy and rapamycin, almost complete remission developed in 71% and 80% of animals, respectively. (The late stage corresponds to complete paralysis of the tail and hind limbs, and at the terminal stage paresis of the front paws is added, which does not allow the animal to turn over from the back to the stomach.) According to Hoffman, these results indicate that combination therapy may be most effective in rapidly progressing paralysis.
The authors note that the underlying observed changes are largely unclear. Therefore, before conducting clinical trials, their proposed approach should be tested on other preclinical models. In addition, the researchers plan to develop gene therapy methods aimed against all proteins involved in the development of multiple sclerosis.
I feel sorry for the mouse...
Article by Geoffrey D. Keeler et al. Gene Therapy-Induced Antigen-Specific Tregs Inhibit Neuro-inflammation and Reverse Disease in a Mouse Model of Multiple Sclerosis is published in the journal Molecular Therapy.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Florida Health: Unique gene therapy prevents, reverses multiple sclerosis in animal model.
25.09.2017