Multiple sclerosis (MS)

Types of patients: the individuals aged over 18 with multiple sclerosis (MS) or disseminated encephalomyelitis (DEM), independent on the disease stage and localization of the process. It is better if the patient has already received standard therapy according to conventional healthcare standards and it has appeared ineffective

Proposed strategies of therapy of MS. We can offer three strategies for the therapy of MS. The first is the standard treatment using modern technologies and disease modifying drugs (DMDs). To date, several drugs from the group of monoclonal antibodies (MCA) have been registered in the Russian Federation for the treatment of relapsing-remitting MS (RRMS): Natalizumab (TYSABRI), Alemtuzumab (LEMPTRADA), and relapsing forms of MS: OKREVA (ocrelizumab) and Ofatumumab (KESINDRA) and others. Still, the frequency of exacerbations may persist, which signals of the patient's resistance to treatment. The use of MCA based DMDs bears the risk of development of severe autoimmune and incurable complications, which should be balanced with its benefits. But there is also another problem: foreign manufacturers (Roshe, Novartis, etc.) have left the Russian pharmaceutical market and the drugs are not always available.  

The second strategy to treat MCA resistant MS is the technology of bone marrow transplantation (Immunotherapy technologies, Immunotherapy techniques, Gene technologies) or autologous hematopoietic personalised therapy transplantation (cellsT). In our hospital we do it together with the bone marrow transplantation center of the Federal State Budgetary Institution National Medical Research Center for Radiology of the Ministry of Health of Russia, a branch of the A.F. Tsyb Moscow Scientific Research Center. We have a large experience of Immunotherapy technologies, Immunotherapy techniques, Gene technologies/cellsT in MS that has been accumulated for almost 20 years (see video) and results in stabilization of the demyelinating process.

Also, there is a third strategy for MS therapy, which we prefer. The third strategy is based on new science-driven ideas on the causes of autoimmune diseases in humans. We consider MS to be the hematopoietic disorder, while demyelination of neurons in the brain is not a cause, but a consequence of this pathology. However, this standing point differs from the conventional opinion of the medical community. We consider MS an immune-associated disease, in which the main cause of the disease is the pathology of the immune system. This is a completely new and innovative approach to the treatment of MS. The approach is called Personalized Adoptive Immunotherapy. It is based on the study of individual genomic and proteomic features of the hematopoiesis of the MS patient. The head of the hospital, Prof. Andrey Stepanovich Bryukhovetskiy, has been treating this disease for more than 20 years. Prof. Bryukhovetskiy has developed and patented the technology of ultra-early molecular biological diagnostics of MS and ALS based on protein markers of the human hematopoietic personalised therapy surface. This method allows diagnosing MS at an extremely early stage of the disease, detecting familial forms of MS, and even preventing the disease in family members with familial (hereditary) MS. Treatment is based on the identification of individual genomic and proteomic changes in the hematopoiesis of each individual MS patient. The pathological clonal hematopoiesis is detected in all MS patients as the main system-forming cause of the disease. The clonality of hematopoiesis underlies the autoimmune genesis of MS and it forms a disease of the blood and blood production system leading to the demyelinating disease of axons of neurons of the brain and spinal cord. To diagnose clonal hematopoiesis, whole genome sequencing of 22,000 genes of blood cells and bone marrow is performed, the proteomic profile of membrane proteins of the cells is studied and mutations in the genes of clonal hematopoiesis are detected, as well as the driver genes characteristics of MS and hematopoiesis clonality. If autoimmune clonal hematopoiesis is confirmed genetically and proteomically in a patient with MS, the patient can be included in our treatment protocol. You can discuss the details of the treatment protocol with our doctor at an in-person consultation.

Therapy goal: Ultra-early molecular biological diagnosis of MS by the profile of membrane proteins of the patient's hematopoietic personalised therapy; arrest of the disease progression and prevention of recurrence of a disabling chronic demyelinating disease through the modification of the body's immune response that damages motor neurons. Switch from mono- and oligoclonal hematopoiesis to polyclonal hematopoiesis to secure the arrest of the pathological demyelinating process in the patient's immune system and brain.

The principle of diagnosis and therapy: In 30 years of genomic and proteomic studies of hematopoietic personalised therapy, our research team established and patented several important scientific evidence. First, we consider MS a disease caused by genomic and postgenomic damage of the hematopoietic personalised therapy, so that the damage and demyelination of axons of motor neurons, cortical neurons, and other neurons of the brain and spinal cord are not the cause of brain disease, but a consequence of postgenomic disease of cells, leading to systemic fatal disorders of human immunity. Therefore, molecular test of the patient's cells helps us diagnose the disease at its earliest stage and determine in a molecular-biological way whether Immunotherapy technologies, Immunotherapy techniques, Gene technologies will be effective in the case. Second, the main pathogenetic component of this disease is the formation of a pathological cells clone, the emergence of which is induced by the molecular biological structural changes in these cells. Third, the pathological clone of cells, leads to the onset of clonal hematopoiesis, which leads to aggression of immunocompetent blood cells (descendants of pathological cells) towards the cells of their own nervous tissue in general and myelin of axons of neurons in MS, in particular. In one case, the adverse environmental factors or the organism itself lead to monoclonal hematopoiesis with one pathological clone or, in other cases oligoclonal hematopoiesis several pathological clones of cells is formed. Fourth, due to the pathological hematopoiesis the descendants of pathological cells form the immune “lethal loop" of one's own immunity, which destroys the myelin of the neural axons. Our approach allows us to offer a fundamentally new pathogenetic therapy for this disease, in which we block the pathological cells clone and restore the polyclonal nature of hematopoiesis.

Methods: At the first stage, pathological hematopoiesis is diagnosed in a patient with MS by molecular genetic and proteomic tests of the patient's cells. If mutations in the genes of hematopoiesis clonality are detected, the CD34+ fraction of the peripheral blood mononuclear cells (PBMCs) is harvested from the patient on a cell separator, using a disposable system; then the cells are cryopreserved, the therapeutic substance, under special basic conditions.  One séance provides the material that is sufficient for the restorative therapy. The obtained cell material is preserved at low temperature. Subsequently, the dominant pathological cells clone is immunosuppressed, the restored cells are administered and the immune response is stimulated. This activates suppressed clones of healthy cells and restores the polyclonal nature of hematopoiesis. Genetic and proteomic diagnostics is repeated in 3 and 6 months to confirm the fact of restoration of polyclonal hematopoiesis. The treatment can arrest the progression of the most forms of MS, including incurable forms.

Result. Our methods permitted stable remission of MS patients after bone marrow transplantation for more than 19 years and 15 years. MS is considered an incurable autoimmune demyelinating disease and it would be absolutely wrong and tactless to claim that we have created a technology to cure this demyelinating disease. We do not aim to cure MS. We aim to stop the progression of it and to increase the life expectancy of these patients, as well as to improve their quality of life without the death risks. We also have some experience in increasing the life expectancy of patients using this protocol.

Over 20 years, about 50 patients with MS have been treated, of which the last protocol has been used in 5 patients, so far. You can get acquainted with the results of treatment in a two-volume guide for doctors, written by our professor of neurology A.S. Bryukhovetskiy and professor of molecular biology Yu.S. Khotimchenko "Cell technologies and personalised medicine in the clinic of nervous diseases", published in 2019.