Remitting Multiple Sclerosis Research Articles

Immune reconstitution therapies: concepts for durable remission in multiple sclerosis

New so-called immune reconstitution therapies (IRTs) have the potential to induce long-term or even permanent drug-free remission in people with multiple sclerosis (MS). These therapies deplete components of the immune system with the aim of allowing the immune system to renew itself. Haematopoietic stem cell transplantation, the oral formulation cladribine and the monoclonal antibodies alemtuzumab, rituximab and ocrelizumab are frequently categorized as IRTs. However, the evidence that IRTs indeed renew adaptive immune cell repertoires and rebuild a healthy immune system in people with MS is variable. Instead, IRTs might foster the expansion of those cells that survive immunosuppression, and this expansion could be associated with acquisition of new functional phenotypes. Understanding immunological changes induced by IRTs and how they correlate with clinical outcomes will be instrumental in guiding the optimal use of immune reconstitution as a durable therapeutic strategy. This Perspectives article critically discusses the efficacy and potential mechanisms of IRTs in the context of immune system renewal and durable disease remission in MS.

The emerging role of serum zinc in motor disability and radiological findings in patients with multiple sclerosis

BackgroundThe role of serum Zinc in the pathogenesis of relapsing remittent multiple sclerosis (RRMS) and its impact on motor disability and radiological findings remains a matter of debate.ObjectivesTo assess the level of serum Zinc in patients with RRMS at time of relapse and during remission and to correlate serum zinc with degree of disability, fatigue, response to disease modifying drugs, and magnetic resonance imaging (MRI) findings.Subjects and methodsA case-control study was carried out on 75 subjects divided into three groups, 25 patients diagnosed as RRMS during relapse, 25 patients during remission, and 25 healthy controls. All included patients were subjected to neurological assessment including Expanded Disability Status Scale (EDSS), Modified fatigue impact scale (MFIS), and Modified RIO score (MRS). Zinc serum level was measured for all patients and controls using direct colorimetric test method. Brain and spine MRI were done for all included patients.ResultsMS patients in relapse and during remission were found to have significantly lower zinc level than the control group (P value = 0.001 and < 0.001 respectively). There was a statistically significant negative correlation between serum zinc level and disease duration, number of relapses in the last 2 years, total number of relapses, EDSS before and after pulse steroids, MRS, MFIS, and MRI lesion load (P value = 0.017, 0.037, 0.001, 0.001, 0.004, 0.005, and 0.001, respectively).ConclusionSerum zinc level is significantly lower in patients with MS than healthy controls. It is negatively correlated with disease duration, number of relapses, motor disability, fatigue, and MRI lesion load.

Clinical Course of Relapsing Remitting Multiple Sclerosis Post-Natalizumab.

Natalizumab is an efficacious disease modifying therapy (DMT) for relapsing remitting multiple sclerosis (RRMS), often limited by risk of progressive multifocal leukoencephalopathy. We describe the clinical course of RRMS patients switched from natalizumab to another DMT. We identified all RRMS patients treated with natalizumab ≥3 months with JC virus antibody positivity who switched to another DMT. Overall, 84 individuals switched DMT with 57 (68%) beginning fingolimod. On fingolimod, survival without a relapse was 74% (55.8-85.6%) at 36 months and survival without disease progression was 78% (62.6-87.6%) at 36 months. In conclusion, fingolimod is an effective therapy post-natalizumab.

Engaging across dimensions of diversity: A cross-national perspective on mHealth tools for managing relapsing remitting and progressive multiple sclerosis

BackgroundSmartphone apps and wearable devices could augment clinical practice by detecting changes in health status for multiple sclerosis (MS). This study sought to investigate potential barriers and facilitators for uptake and sustained use in (i) people with both relapsing remitting MS (RRMS) and progressive MS (PMS) and (ii) across different countries. MethodsTwenty four participants with MS took part in four focus groups held in three countries (2 in the UK, 1 in Spain, and 1 in Italy) to investigate potential barriers and facilitators for mHealth technology. A systematic thematic analysis was used to extract themes and sub-themes. ResultsFacilitators and barriers were organised into functional technology-related factors and non-functional health-related and user-related factors. Twelve themes captured all requirements across the three countries for both RRMS and PMS. Key requirements included accommodation for varying physical abilities, providing information and memory aids. Potential negative effects on mood and providing choice and control as part of overcoming practical challenges were identified. ConclusionsWe took a cross-national perspective and found many similarities between three European countries across people with RRMS and PMS. Future provision should accommodate the key requirements identified to engage people with MS in scalable mHealth interventions.

Efficacy, tolerability and safety of the treatment with teberif: the results of a 2-year randomized clinical trial of treatment naïve patients with remitting multiple sclerosis, who have not received DMT, after switching from other interferon β-1a

To evaluate efficacy, safety, and tolerability of the treatment with teberif/interferon β-1a, to analyze safety, tolerability and dynamics of key efficacy variables after switching from referent drug rebif to biosimilar teberif in patients with remitting multiple sclerosis (RMS). During the main period of the international multicenter randomized study patients were randomized to receive treatment with teberif for 52 weeks, or rebif for 52 weeks, or placebo for 16 weeks to evaluate efficacy and safety of treatment. After the main study period, patients were group-independently switched to take open-label teberif treatment during the next 48 weeks. The analysis of multiple evaluation parameters of the efficiency during the 1st study period (blinded) and the 2nd study period (open-label) has shown that teberif and rebif demonstrate equivalent efficacy and stable 2-year efficacy of teberif was proven. There were no significant differences between teberif and rebif for all safety, and tolerability parameters. Switching from rebif to teberif didn't influence treatment efficacy. The 2-year study results confirmed a biosimilar teberif's benign tolerability and expected safety profile to other interferons β-1a in patients with RMS.

Factors regulating the activity of b-lymphocytes, as potential biomarkers of multiple sclerosis

To assess the possibility of using serum levels of chemokine CXCL13, B-cell activating factor (BAFF), interleukin 1 and 17 (IL-10, IL-17) as markers of the development/progression of multiple sclerosis (MS). Sixty-seven patients with MS in remission and 14 healthy volunteers were examined. The levels of BAFF, CXCL13 and the main products of Th17 and Treg - interleukin 17 (IL-17) and IL-10 in the serum were determined, their relationship with clinical characteristics of MS during remission was assessed. The content of IL-17 and BAFF in the serum of patients with MS did not differ significantly from the control group, and the levels of IL-10 and CXCL13 were lower than the corresponding indicators of healthy donors. In patients with MS, no correlation was found between IL-17, IL-10, BAFF and clinical characteristics of MS. The level of CXCL13 correlated with quality of life, fatigue, clinical and functional status of patients. According to the results of this study, BAFF and CXCL13 cannot be proposed as diagnostic biomarkers of MS.

The application of the pulsed low-frequency electrostatic field in pediatrics

One of new methods for the physiotherapeutic treatment in pediatrics is the application of the pulsed low-frequency electrostatic field the action of which is based on the effects of deep resonant vibration on the affected tissue region with the minimal mecha-nical impact. Under the influence of the electrostatic field, the tissues at the site of interest become tightened and descend which causes their vibration due to the alternation of the pulses and intervals between them. The fast consecutive repetition of this process results in rhythmical deformation of the tissues. The electrostatic pulses are responsible for the increased friction between separate parts of the tissues while in the intervals between the pulses the tissue elastically resists their influence. In this way, the tissues subjected to such influence 'are pumped over' throughout their depth. It leads to the restoration of elasticity and mobilization of separate fibers and layers inside the tissue as well as to the development and improvement of the blood flow in the tissues and their blood supply. During the recent years, a large number of reports have been published in the literature concerning the possibilities of application of the pulsed low-frequency electrostatic field for the treatment and prevention of various di-seases in the children, including both monotherapy and its combination with other therapeutic modalities. The favourable action of the pulse low-frequency electrostatic field on the clinical course of bronchial asthma, mucoviscidosis, I and II degree scoliosis in the young children, remittent multiple sclerosis in the adolescents has been demonstrated. The data obtained give evidence of the high effectiveness of the proposed method, its excellent tolerance, and a wide range of beneficial effects on the main pathogenetic components of the diseases which creates the good prerequisites for the further active introduction of the therapeutic phy-sical factors in the practical work of the children's medical organizations.

Interferon beta - lek kojim je započeta revolucija u lečenju multiple skleroze

Multiple sclerosis is a chronic, inflammatory, demyelinating and neurodegenerative disease of the central nervous system. The etiology is unknown, and it is estimated that about 2.5 million people all around the world are suffering from this disease. It is the most common cause of non-traumatic disability in young adults. The clinical presentation is very variable and unpredictable. There are three basic forms of the disease - relapsing remitting, primary progressive and secondary progressive multiple sclerosis. The prognosis for these patients has changed since 1993, when the first disease modifying therapy - interferon beta, was approved. Interferon beta reduces the number of relapses, reduces the number of hyper intense lesions on T2 sequences of endocranial MRI, mildly delaying the progression of the disease. Interferon beta is also used in pediatric population. It is considered to be generally safe, since it does not increase the likelihood of developing malignancy and opportunistic infections.

Micro-RNA 18b and interleukin 17A profiles in relapsing remitting multiple sclerosis

BackgroundThe involvement of micro RNAs (miRNAs) in multiple sclerosis (MS) has been recently explored. Up-regulated miRNAs may play critical roles in MS pathogenesis and may be used as a signature for MS. Besides, the role of inflammatory cytokines has been long established with recent focus on interleukin-17 (IL-17). ObjectiveTo evaluate the level of expression miR-18b in relation to IL-17A in relapsing remitting (RR) MS patients during relapse and remission Subjects and methodsTwenty-eight RRMS patients and 26 age and sex matched control subjects were included. Serum miR-18b was assessed by quantitative real-time PCR, and serum level of IL-17A was measured by ELISA. ResultsSerum miR-18b expression was higher in relapse compared with remission and with controls (24.8 ± 21.91 vs 2.49 ± 0.97 vs 1 ± 0.36 respectively; P < 0.001). Serum IL-17Awas higher in MS patients during relapse than during remission and controls (8.49 ± 1.26 vs 5.78 ± 2.27 vs 4.18 ± 2.13, respectively; P < 0.001). No correlations existed between miR-18 and IL-17 in MS patients during relapse (r = 0.35; P = 0.22) or remission (r = 0.340; P = 0.234). ConclusionUpregulation of miR-18 during relapse in patients with RRMS points to a possible contribution to the pathogenesis of the inflammatory process in MS. The lack of a significant correlation between upregulated miR-18 and IL-17A implicates that the influence of miR-18 may be exhibited via another inflammatory pathway.

Immune reconstitution therapy (IRT) in multiple sclerosis: the rationale.

Immunotherapy of multiple sclerosis (MS) and other neuroimmune diseases is rapidly evolving. For the past 25years, there has been an accelerating inclusion of new immunomodulating drugs. Based on their molecular construction and their basic mechanism of action, immunotherapeutic agents belong to the following categories: (1) cytotoxic drugs, (2) synthetic immunomodulators, (3) monoclonal antibodies, (4) vaccines (T cell vaccines, antigen vaccines), (5) oral tolerizing agents, (6) modalities that act as indirect immunosuppressants (plasmapheresis, intravenous immunoglobulins [IVIG]), and (7) cellular therapies. MS immunotherapies may also be classified in a different way, into treatments that are given continuously (chronic treatments) and medications that are applied intermittently (IRTs). The principle behind the latter is depletion of the immune system that allows it to rebuild itself. Upon its reconstitution/resetting, the immune system regains the ability to respond to infections and survey the periphery for cancer. An IRT by definition is given at short intermittent courses and not continuously. IRT modalities were shown to induce long-term remission of MS that, in some cases, is close to the definition of a "cure." There are cohorts of patients having been treated with the IRTs, alemtuzumab, and HSCT, who experience-under these modalities-no evidence of disease activity (NEDA) for over 10years. Most importantly, IRTs cause radical changes in the lymphocyte repertoire after the reconstitution phase that may explain the long-term beneficial effects of IRT and the possibility of re-induction of self-tolerance to self/myelin antigens. In comparison, a chronic treatment cannot result in cure of the autoimmune reactivity, because it only blocks the immune system, as long as it is given; it cannot therefore radicallyaffect the immunopathogenesis of the disease. The risks of adverse events related to immune suppression (such as opportunistic infections and secondary malignancies)with IRTs are lower andfront-loaded, whereas the common side effects of chronic immunomodulationare higher andaccumulate with time. In conclusion, IRT provides a novel concept for MS therapy with substantial advantages over chronic immunosuppression. IRT therapies have shown a significantly higher level of efficacy in MS. The "Holy grail" of thetreatment of autoimmunity, which is to re-induce the disrupted self-tolerance, seems to be achievable-at least in part-with this approach. Moreover, the benefits of IRT, administered in short pulses, include significantly higher adherence to treatment and lower risks for accumulative side effects that are typically associated with chronic immunosuppression.

Transbulbar B-Mode Sonography for Clinical Phenotyping Multiple Sclerosis

The aim of this study was to assess putative differences in optic nerve sheath diameter (ONSD) and associated clinical/paraclinical variables between relapsing remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) patients. We examined 60 relapse-free MS patients and 35 healthy controls by means of transbulbar B-mode sonography (TBS). Expanded disability status scale (EDSS) values were from 3 to 4 indicated patients with a transitional RR to SP phenotype. Mean ONSD was significantly lower in MS patients. Mean ONSD measured at 5 mm from the eyeball (ONSD5) was significantly lower in SP than in RR patients, while ONSD measured at 3 mm from the eyeball (ONSD3) was statistically higher in RR than in the transitional group. The myelination index (MI), i.e., the ratio of ONSD3 to ONSD5, was used to assess the relative myelination of the optic nerve (ON). Higher ONSD5 and MI (0.90) corresponded to patients with the RR phenotype having a mean EDSS of 2.0; lower MI (0.84) clustered the transitional patients having a mean EDSS of 3.7. Finally, lower MI with low ONSD3 identified the SP phenotype having a mean EDSS ≥ 4.0. The TBS in MS highlights chronic optic neuropathy, caused by early subclinical axonal loss and demyelination.

A Comparative Placebo-Controlled Clinical Trial of the Efficacy and Safety of Interferon β-1a Formulations for S.C. Administration in Patients with Remitting Multiple Sclerosis: First-Year Results

Objectives. To demonstrate equivalence of the efficacies of the drugs Teberif (BCD-033, interferon β-1a) and Rebif (interferon β-1a) in patients with remitting multiple sclerosis (RMS). Materials and methods. A multicenter, double-blind, placebo-controlled, comparative, randomized phase III trial included 163 patients with diagnoses of MS. Patients were randomized to the Teberif, Rebif, and placebo groups at a ratio of 1:1:1. Results and conclusions. Analysis of efficacy after 52 weeks of the trial demonstrated equivalence between the study drug Teberif and the original formulation Rebif in patients with RMS. Evaluation of primary endpoint results – CUA (combined unique active lesions, i.e., the total number of MRI T1 plaques and new T2 plaques or cases of increases in T2 plaques without double counting) – demonstrated that there were no significant differences (0.727 ± 1.042 and 0.652 ± 1.059, p = 0.7354, Student’s t test) between the Teberif and Rebif groups. There were no statistically significant between-group differences in other MRI indicators or measures associated with exacerbations. The safety profile and tolerance of Teberif were satisfactory and comparable with the safety and tolerance profile of Rebif. These data provide evidence of therapeutic equivalence of these drugs, which may provide grounds for the use of the interferon β-1a bioanalog in patients with RMS.

Characterization of circulating gamma-delta T cells in relapsing vs remission multiple sclerosis

We characterized circulating gamma-delta T cells in relapsing-remitting multiple sclerosis (RRMS) patients, during remission and relapse phases. In relapse, we observed a decrease of circulating CCR5+ γδ TEMRA cell subset, together with a decrease in EOMES and granzyme B mRNA expression in γδ T cells, suggesting a reduction of the cytotoxic potential of this subset. Moreover, we also found a higher frequency of IFNγ+ γδ T cells, which may indicate that these cells are assuming a more regulatory function associated to a Th1 profile. These results suggest a specific release from the periphery of a particular γδ T cell subset, expressing CCR5 and belonging to an effector compartment, supporting the idea that γδ T cells could play a role in MS relapse.

Efficacy, tolerability, quality of life and spasticity in outpatients with remitting multiple sclerosis (RMS) treated with glatiramer acetate (GA) - Results of an observational study

Efficacy, tolerability, quality of life and spasticity in outpatients with remitting multiple sclerosis (RMS) treated with glatiramer acetate (GA) - Results of an observational study

Ocrelizumab: A New B-cell Therapy for Relapsing Remitting and Primary Progressive Multiple Sclerosis.

To review the pharmacology, pharmacokinetics, efficacy, and safety of ocrelizumab, a new B-cell-targeted therapy for multiple sclerosis (MS). A comprehensive search of PubMed and OVID/MEDLINE was conducted using search terms ocrelizumab and multiple sclerosis using the date range of 1946 through October 2017. All English-language, human-subject articles related to ocrelizumab and MS were evaluated. Ocrelizumab was approved in March 2017 for the treatment of relapsing or primary progressive MS (PPMS). A phase II trial established 600 mg intravenously every 6 months as the preferred dosing schedule. Two phase III trials evaluated the efficacy of ocrelizumab in patients with relapsing remitting MS, and individual and pooled analysis demonstrated a significant reduction in annualized relapse rate ( P < 0.001 pooled), disability progression at 12 weeks ( P < 0.001 pooled), and gadolinium-enhancing lesions on magnetic resonance imaging (MRI; P < 0.001). Patients with PPMS were evaluated in a third phase III trial, which showed a significant decrease in disease progression at 12 weeks ( P = 0.03) and volume of T2-weighted lesions on MRI ( P < 0.001). As with other monoclonal antibodies, adverse effects seen with ocrelizumab were primarily infusion-related reactions and infection. Ocrelizumab demonstrated efficacy in the treatment of relapsing and PPMS and is the first therapy approved for patients with PPMS.

Significance of elevated Prohibitin 1 levels in Multiple Sclerosis patients lymphocytes towards the assessment of subclinical disease activity and its role in the central nervous system pathology of disease

Multiple Sclerosis (MS) is an autoimmune-neurodegenerative disorder managed therapeutically by modulating lymphocytes activity which has potential in disease management. Prohibitin 1(PHB) that controls the reactive oxygen species (ROS) and present on the activated lymphocytes have significance in the therapy of MS as esters of fumaric acid that regulates ROS is in phase II/III clinical trials. Thus, we evaluated the expression levels of PHB1 in experimental autoimmune encephalomyelitis (EAE), the animal model of MS and on MS patient’s lymphocytes. PHB levels in brain tissue of EAE animals were determined by immunoblotting and on blood lymphocytes from MS relapse, Remission, Optic Neuritis, Neurological controls and Healthy volunteers by FACS using anti-PHB and anti-CD45 antibodies. We observed significant elevation of PHB in EAE brains (91.0 ± 17.59%) vs controls (29.8 ± 12.9%) (p = 0.01) and on lymphocytes of MS patients in acute (73.5 ± 11.20%) or relapsing (69.3 ± 17.33%) phase compared to remission (45.9 ± 8.08%) [p = 0.034 acute vs remission; p = 0.004 relapse vs remission]. Up regulation of PHB in relapsing vs remission MS patients imply the potential use of PHB to clinically evaluate subclinical disease status towards prognosis of an oncoming relapse. Elevated PHB levels in EAE brains signify the role of PHB in regulating ROS and implies PHB’s role in oxidative stress.

Fatigue in multiple sclerosis: The contribution of resting-state functional connectivity reorganization

Objectives: To investigate resting-state functional connectivity (RS-FC) of the default-mode network (DMN) and of sensorimotor network (SMN) network in relapsing remitting (RR) multiple sclerosis (MS) patients with fatigue (F) and without fatigue(NF). Methods: In all, 59 RRMS patients and 29 healthy controls (HC) underwent magnetic resonance imaging (MRI) protocol including resting-state fMRI (RS-fMRI). Functional connectivity of the DMN and SMN was evaluated by independent component analysis (ICA). A linear regression analysis was performed to explore whether fatigue was mainly driven by changes observed in the DMN or in the SMN. Regional gray matter atrophy was assessed by voxel-based morphometry (VBM). Results: Compared to HC, F-MS patients showed a stronger RS-FC in the posterior cingulate cortex (PCC) and a reduced RS-FC in the anterior cingulated cortex (ACC) of the DMN. F-MS patients, compared to NF-MS patients, revealed (1) an increased RS-FC in the PCC and a reduced RS-FC in the ACC of the DMN and (2) an increased RS-FC in the primary motor cortex and in the supplementary motor cortex of the SMN. The regression analysis suggested that fatigue is mainly driven by RS-FC changes of the DMN. Conclusions: Fatigue in RRMS is mainly associated to a functional rearrangement of non-motor RS networks.

Metabolomic profiling of CSF in multiple sclerosis and neuromyelitis optica spectrum disorder by nuclear magnetic resonance.

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are inflammatory diseases of the central nervous system. Although several studies have characterized the metabolome in the cerebrospinal fluid (CSF) from MS and NMOSD patients, comparative analyses between them and between the relapse and the remission of each disease have not been performed. Both univariate and multivariate analyses were used to compare 1H-NMR spectra of CSF from MS, NMOSD, and healthy controls (HCs). The statistical analysis showed alterations of eight metabolites that were dependent on the disease. Levels of 2-hydroxybutyrate, acetone, formate, and pyroglutamate were higher and levels of acetate and glucose were lower in both MS and NMOSD. Citrate was lower in MS patients, whereas lactate was higher in only NMOSD specifically. The shared feature of metabolic changes between MS and NMOSD may be related to altered energy metabolism and fatty acid biosynthesis in the brain. Another analysis to characterize relapse and remission status showed that isoleucine and valine were down-regulated in MS relapse compared to MS remission. The other metabolites identified in the disease comparison showed the same alterations regardless of disease activity. These findings would be helpful in understanding the biological background of these diseases, and distinguishing between MS and NMOSD, as well as determining the disease activity.

CXCL10 and CXCL13 chemokines in patients with relapsing remitting and primary progressive multiple sclerosis

ObjectivesMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system characterized by a variable clinical course. Different pathogenic mechanisms responsible for relapsing remitting (RRMS) and primary progressive multiple sclerosis (PPMS) are modulated by immunological process with important role of chemokine network. CXCL10 and CXCL13 chemokines act as chemoattractants and modulators of proinflammatory reactions promoting process of demyelination. In the present study, we investigated the concentrations of CXCL10 and CXCL13 in serum and cerebrospinal fluid (CSF) of patients with RRMS and PPMS. Materials and methodsThe study groups comprised 25 RRMS patients (39,5±12years), 24 PPMS patients (49,9±10,5years), 31 healthy individuals (36±10,4years) with tension headache without symptoms of inflammatory diseases. A quantitive test kit based on ELISA has been used for chemokines measurement. Correlations analysis between the levels of CXCL10, CXCL13 and patient age, duration of MS, EDSS and IgG index were done. ResultsThe mean concentration of CXCL10 in the CSF was statistically significantly higher in RRMS in comparison with the control group. The mean concentration of CXCL13 in the CSF was significantly higher in RRMS and PPMS than in the control group. The results have shown that in the stable phase of MS without relapse, mean concentration of CXCL10 and CXCL13 in CSF did not differ significantly between RRMS and PPMS. In PPMS a positive correlation between IgG index and CSF CXCL10 level or CSF CXCL13 level was observed. In RRMS a positive correlation between IgG index and CSF CXCL13 level was observed. ConclusionsThese data indicate involvement of CXCL10 and CXCL13 chemokines in immunopathogenetic mechanisms in MS. There was no significant difference between mean CXCL10 or CXCL13 concentrations in the CSF in both RRMS and PPMS patients. No significant correlations were found between patient age and chemokines levels in theCSF in all groups. It suggest that these chemokines play similar role in inflammatory process despite more pronounced neurodegenerative process in PPMS.

Treatment with Ex Vivo Expanded Autologous Regulatory CD4+CD25+Foxp3+CD127low T Cells Restores the Balance of the Immune System in Patients with Remitting Multiple Sclerosis

Objective. To assess the clinical efficacy and safety of autologous (patient’s own) Treg cells – CD4+CD25+Foxp3+CD127low – isolated from the blood of patients with remitting multiple sclerosis (RMS). Patients with autoimmune diseases have decreased numbers and impaired suppressor functions of peripheral Treg cells circulating in the blood. With the aim of correcting the defect in peripheral Treg, precursor cells were isolated and expanded outside the patient’s body (ex vivo), and an increased number of autologous (patient’s own) Treg cells were given in the form of Treg vaccine. Materials and methods. An ex vivo cultivation method was developed which increased the number of Treg cells by factors of 30–40 over 5–7 days. Ex vivo expanded cells contained more than 90% CD4+CD25+Foxp3+CD127low Treg cells and had high levels of suppressor activity. A total of 14 patients with MS took part in a pilot trial and received s.c. ex vivo expanded Treg cells at doses of (2.8–4.5)·108 cells per injection. Observations were continued for one year. Results and discussion. Blood Treg levels in patients increased by factors of 1.5–2. No adverse reactions were seen during the study period; exacerbation frequency decreased, and the index of disability stabilized. It is suggested that ex vivo expanded Treg may compensate for impairments to the functions of peripheral Treg and can be used for the adoptive immunotherapy of RMS.