Chronic Progressive Multiple Sclerosis Patients Research Articles

Therapeutic Plasmapheresis with Albumin Replacement in Alzheimer's Disease and Chronic Progressive Multiple Sclerosis: A Review.

Background: Reducing the burden of beta-amyloid accumulation and toxic autoimmunity-related proteins, one of the recognized pathophysiological markers of chronic and common neurological disorders such as Alzheimer’s disease (AD) and multiple sclerosis (MS), may be a valid alternative therapy to reduce their accumulation in the brain and thus reduce the progression of these disorders. The objective of this review was to evaluate the efficacy of plasmapheresis (PP) in AD and chronic progressive MS patients (in terms of improving clinical symptoms) and to analyze its safety and protocols. Methods: Articles related to this topic and published without time limitations in the Medline, and Cochrane databases were reviewed. Results: In AD patients, PP reduced amyloid beta (Aβ) levels in the brain, accompanied by a tendency towards cognitive stabilization, and improved language and verbal fluency. In regards to structural and functional brain changes, PP reduced brain volume and favored the stabilization, or absence, of the progression of perfusion. In chronic progressive form of MS patients, PP improved neurological deficits in 20–70% of patients with a chronic progressive form of MS, and restored interferon (IFN) responsiveness, which was not accompanied by any image change in brain plaques. Conclusions: Therapeutic plasmapheresis with albumin replacement is a promising strategy for reducing Aβ mediated toxicity and slowing the progression of the disorder. Some patients with chronic progressive forms of MS show improvement in neurological deficits. The features of AD and MS patients who benefit most from this approach need further research.

On the road to new treatments for multiple sclerosis: targeting dendritic cell migration into the central nervous system.

On the road to new treatments for multiple sclerosis: targeting dendritic cell migration into the central nervous system.

One-time intrathecal triamcinolone acetonide application alters the redox potential in cerebrospinal fluid of progressive multiple sclerosis patients: a pilot study.

Cerebrospinal fluid analysis may provide insight into the interplay between chronic inflammation and response to treatment. To demonstrate the impact of one intrathecal triamcinolone injection on the redox potential and on ascorbyl radical appearance in the cerebrospinal fluid of chronic progressive multiple sclerosis patients. A total of 16 patients received 40 mg triamcinolone. Electron-spin resonance spectroscopy measured the oxidation range after copper ion [Cu (II)] addition and ascorbyl-radical bioavailability. There was an increase of Cu (II) ion absorption, which reflects an augmented content of reduced proteins. Ascorbyl radicals were present in contrast to healthy controls according to the literature. Intrathecal steroid application alters the redox potential in cerebrospinal fluid. Our findings support the beneficial role of steroids on oxidative stress generally demonstrated by ascorbyl radical appearance. Reactive oxygen species decline is necessary for an upregulated production of reduced proteins.

Prevalence of neurofascin-155 antibodies in patients with multiple sclerosis

IntroductionAntibodies against neurofascin, an axo-glial protein located around the node of Ranvier, have been shown to contribute to axonal pathology both in vitro and in experimental autoimmune encephalomyelitis models. Moreover, small case studies have reported anti-NF antibodies in samples from patients with progressive multiple sclerosis (MS). Patients and methodsBuilding up on this observation, we compared the anti-NF reactivity in serum samples from 83 chronic progressive MS (PMS) patients to those with relapsing remitting MS (RRMS, n=159) and 50 healthy controls. Anti-NF seroreactivity was quantified by enzyme-linked immunosorbent assay using recombinant rat neurofascin. In addition, to identify a potential intrathecal anti-NF antibody synthesis, we calculated the specific antibody index in paired cerebrospinal fluid and serum samples from MS patients with positive anti-NF seroreactivity. ResultsPrevalence of anti-NF seroreactivity in PMS patients (4.8%; all with primary progressive MS) was significantly higher than that detected in RRMS (0.6%; p=0.030). However, we found no significant difference between PMS patients and healthy controls (2.0%; p=0.408). MS patients with positive anti-NF reactivity experienced an above-average progression of disability compared to MS natural-history controls. Anti-NF-specific intrathecal antibody synthesis was not detected in MS patients with positive anti-NF seroreactivity. ConclusionsAlthough present only in a minor subgroup, seroprevalence of anti-NF reactivity was significantly more frequent in patients with PMS than in those with RRMS, but was also occasionally found in healthy controls. Further prospective studies are warranted to investigate whether anti-NF antibodies anticipate disease progression.

Torque teno virus (TTV) in multiple sclerosis patients with different patterns of disease

Torque teno virus (TTV) is highly prevalent in the general population worldwide. The relationship that TTV establishes with the central nervous system (CNS) of infected hosts is not clear but it is suspected that TTV infection of the CNS lead to increased local expression of inflammatory mediators that may play a role in the pathogenesis of multiple sclerosis (MS). The prevalence and load of TTV in serum and cerebrospinal fluid (CSF) of 207 MS patients and 93 age- and sex-matched healthy controls by qPCR designed on the untranslated region were analyzed. TTV DNA was not detected in CSF, TTV prevalence in serum was similar in MS patients (76.8%) compared to healthy controls (76.3%). Sub analyses performed in MS patients stratified on the basis of clinical phenotypes indicated that TTV viremia was significantly lower in individuals with relapsing remitting compared to chronic progressive disease. Notably, viremia was increased in primary progressive, compared to secondary progressive MS patients, and in relapsing remitting MS patients during quiescent compared to relapsing phases of disease. Since TTV interacts with toll-like receptor (TLR) stimulating the production of inflammatory cytokines, TLR9 expression were examined, showing that it was augmented on monocytes of chronic progressive MS patients, in whom higher TTV viremia was present, but this did not correlate with a distinct pattern of cytokine production. Overall these findings suggest that, although TTV infects the same proportion of MS patients and healthy controls, the levels of replication of the virus differ among patients, being correlated with the clinical phenotype of disease.

Dietary interventions for multiple sclerosis

Clinical and experimental data suggest that certain dietary regimens, particularly those including polyunsaturated fatty acids (PUFAs) and vitamins, might improve outcomes in people with multiple sclerosis (MS). Diets and dietary supplements are much used by people with MS in the belief that they might improve disease outcomes and overcome the effectiveness limits of conventional treatments.This is an update of the Cochrane review "Dietary intervention for multiple sclerosis" (first published on The Cochrane Library 2007, Issue 1). To answer MS patients' questions regarding the efficacy and safety of dietary regimens for MS. Can changes in dietary habits be an effective intervention for MS patients? Are the potential side effects of these interventions known, and have they been measured? Are potential interactions between dietary interventions and other curative or symptomatic treatments known and have they been studied? We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (November 2011), CENTRAL (The Cochrane Library 2011, Issue 4), MEDLINE (PubMed) (1966 to November 2011), EMBASE (embase.com) (1974 to November 2011) and reference lists of papers found. All controlled trials (randomised controlled trials (RCTs) and controlled clinical trials (CCTs)) on a specific dietary intervention, diet plan or dietary supplementation, except for vitamin D supplementation, compared to no dietary modification or placebo were eligible. Two review authors independently selected articles, assessed trial quality and extracted data. Data were entered and analysed in RevMan.Dichotomous data were summarised as relative risks (RR) with 95% confidence intervals (95% CI) using a random-effects model in the presence of heterogeneity (I² > 60%). Continuous data were analysed using weighted mean differences, determined by the difference between the pre- and post-intervention changes in the treatment and control groups. Six RCTs that investigated PUFAs emerged from the search strategy, accounting for 794 randomised patients.PUFAs did not have a significant effect on disease progression at 24 months. Omega-6 fatty acids (11 to 23 g/day linoleic acid) didn't show any benefit in 144 MS patients (RR 1.04, 95% CI 0.66 to 1.63). Linoleic acid (2.9 to 3.4 g/day) had no benefit in 65 chronic progressive MS patients (RR 0.78, 95% CI 0.43 to 1.42). Omega-3 fatty acids had no benefit in 292 relapsing remitting MS patients (RR 0.82, 95% CI 0.65 to 1.03, P = 0.08).Slight potential benefits in relapse outcomes were associated with omega-6 fatty acids in some studies, however these findings were limited by the reduced validity of the endpoints. No judgements about safety or patient-reported outcomes were possible. In general, trial quality was poor.No studies on vitamin supplementation and allergen-free diets were analysed as none met the eligibility criteria, mainly due to lack of clinical outcomes. PUFAs seem to have no major effect on the main clinical outcome in MS (disease progression), but they may tend to reduce the frequency of relapses over two years. However, the data that are available are insufficient to assess a real benefit or harm from PUFA supplementation because of their uncertain quality.Evidence on the possible benefits and risks of vitamin supplementation and antioxidant supplements in MS is lacking. More research is required to assess the effectiveness of dietary interventions in MS.

High dose antigen treatment with a peptide epitope of myelin basic protein modulates T cells in multiple sclerosis patients

One of the auto-antigens aberrantly targeted in Multiple sclerosis is myelin basic protein (MBP). In this study, chronic progressive multiple sclerosis (CPMS) patients receiving the experimental drug MBP8298, on a compassionate care trial, were examined before and after high dose peptide treatment for their circulating regulatory T-cell numbers and their responses to the common mitogens, phytohemagglutinin and poke-weed mitogen. Peripheral blood mononuclear cells (PBMCs) isolated from these patients before treatment displayed anergy upon stimulation with phytohemagglutinin; measured through reduced proliferation, IFN-γ and IL-17A secretion in an in vitro cell culture system. 6 Weeks and 6months after treatment their PBMCs displayed a reversal of anergy with phytohemagglutinin stimulation. There was also a marked increase in their CD4+CD25+hiFoxP3+ T-cells regulatory T-cells. These results suggest that high dose MBP8298 treatment has a profound effect on the circulating T-cells of CPMS patients, capable of reversing peripheral anergy and establishing T regulation.

Meningeal and cortical grey matter pathology in multiple sclerosis

Although historically considered a disease primarily affecting the white matter of the central nervous system, recent pathological and imaging studies have established that cortical demyelination is common in multiple sclerosis and more extensive than previously appreciated. Subpial, intracortical and leukocortical lesions are the three cortical lesion types described in the cerebral and cerebellar cortices of patients with multiple sclerosis. Cortical demyelination may be the pathological substrate of progression, and an important pathologic correlate of irreversible disability, epilepsy and cognitive impairment. Cortical lesions of chronic progressive multiple sclerosis patients are characterized by a dominant effector cell population of microglia, by the absence of macrophagic and leukocytic inflammatory infiltrates, and may be driven in part by organized meningeal inflammatory infiltrates. Cortical demyelination is also present and common in early MS, is topographically associated with prominent meningeal inflammation and may even precede the appearance of classic white matter plaques in some MS patients. However, the pathology of early cortical lesions is different than that of chronic MS in the sense that early cortical lesions are highly inflammatory, suggesting that neurodegeneration in MS occurs on an inflammatory background and raising interesting questions regarding the role of cortical demyelination and meningeal inflammation in initiating and perpetuating the disease process in early MS.

Brain Viscoelasticity Alteration in Chronic-Progressive Multiple Sclerosis

IntroductionViscoelastic properties indicate structural alterations in biological tissues at multiple scales with high sensitivity. Magnetic Resonance Elastography (MRE) is a novel technique that directly visualizes and quantitatively measures biomechanical tissue properties in vivo. MRE recently revealed that early relapsing-remitting multiple sclerosis (MS) is associated with a global decrease of the cerebral mechanical integrity. This study addresses MRE and MR volumetry in chronic-progressive disease courses of MS.MethodsWe determined viscoelastic parameters of the brain parenchyma in 23 MS patients with primary or secondary chronic progressive disease course in comparison to 38 age- and gender-matched healthy individuals by multifrequency MRE, and correlated the results with clinical data, T2 lesion load and brain volume. Two viscoelastic parameters, the shear elasticity μ and the powerlaw exponent α, were deduced according to the springpot model and compared to literature values of relapsing-remitting MS.ResultsIn chronic-progressive MS patients, μ and α were reduced by 20.5% and 6.1%, respectively, compared to healthy controls. MR volumetry yielded a weaker correlation: Total brain volume loss in MS patients was in the range of 7.5% and 1.7% considering the brain parenchymal fraction. All findings were significant (P<0.001).ConclusionsChronic-progressive MS disease courses show a pronounced reduction of the cerebral shear elasticity compared to early relapsing-remitting disease. The powerlaw exponent α decreased only in the chronic-progressive stage of MS, suggesting an alteration in the geometry of the cerebral mechanical network due to chronic neuroinflammation.

Benefit of repetitive intrathecal triamcinolone acetonide therapy in predominantly spinal multiple sclerosis: prediction by upper spinal cord atrophy

Intrathecal injection of triamcinolone acetonide (TCA) has been shown to provide substantial benefit in a subset of progressive multiple sclerosis (MS) patients with predominant spinal symptoms. We examined whether atrophy of the upper spinal cord (USC) as measured by MRI can serve as a predictive marker for response to repetitive intrathecal TCA application. Repetitive administration of 40 mg TCA was performed in 31 chronic progressive MS patients up to six times within 3 weeks. Expanded Disability Status Scale (EDSS) and maximum walking distance (WD) were assessed before and after the treatment cycle. Cervical 3D T1-weighted images were acquired on a 1.5T scanner at baseline. Mean cross-sectional area of the USC was determined using a semi-automated volumetry method. Results were compared with a group of 29 healthy controls to group patients into those with and without atrophy. Results show a negative correlation between the degree of USC atrophy and treatment benefit. A higher treatment benefit in patients with little USC atrophy but short initial maximum WD was observed. Absence of USC atrophy as measured on MRI is a predictive marker for intrathecal TCA therapy outcome in progressive MS. Patients with initial poor walking abilities, but only little or no atrophy, benefited most from TCA therapy.

Multiple Sclerosis, Cannabinoids, and Cognition

Multiple Sclerosis, Cannabinoids, and Cognition

Efficacy of Mitoxantrone and Intrathecal Triamcinolone Acetonide Treatment in Chronic Progressive Multiple Sclerosis Patients

Treatment approaches are rare for chronic progressive patients with multiple sclerosis (MS). Objective was to evaluate the clinical benefit of repeated intrathecal application of the sustained release steroid triamcinolone acetonide or the administration of mitoxantrone (MIX) in 2 similar cohorts of chronic progressive patients with MS in an open-label fashion. Expanded Disability Status Scale scores significantly decreased after the first 6 intraspinal triamcinolone acetonide injections, which were performed every third day, and then remained stable. Walking distance significantly increased and did not reduce until the end of the 1-year-long trial period. Mitoxantrone treatment did not improve the Expanded Disability Status Scale score; however, no further significant deterioration appeared. Walking distance did not significantly decrease. Both treatment regimens were safe; the patients experienced nearly no adverse effects. Triamcinolone acetonide application provided a clinical benefit, whereas MIX administration prevented further worsening of MS symptoms. We stress that only specialists with a broad experience in intraspinal triamcinolone acetonide application and MIX administration should perform both kinds of therapy only after a careful information and risk-benefit evaluation in cooperation with the patient. Future trials will show the efficacy of combination of both treatment approaches in chronic progressive patients with MS.

Corticosteroid resistance in a subpopulation of multiple sclerosis patients as measured by ex vivo dexamethasone inhibition of LPS induced IL-6 production

We assessed corticosteroid sensitivity in multiple sclerosis (MS) patients compared to control subjects, using an in vitro assay of dexamethasone (Dex) inhibition of lipopolysaccharide (LPS) stimulated-blood interleukin-6 production. Significantly higher concentrations of dexamethasone were needed to obtain 50%-inhibition (ID 50) of in vitro LPS stimulated interleukin (IL)-6 production (28.4×10 −7 M) in relapsing–remitting MS (RRMS) patients compared to chronic progressive MS (CPMS) patients (6.2×10 −7 M) or compared to controls (3.0×10 −7 M). We also found a trend towards worsening of clinical status over time with increasing corticosteroid resistance. These data suggest that corticosteroid sensitivity may be a factor in the pathogenesis and could be used for prognosis of MS.

Therapy with glatiramer acetate for multiple sclerosis.

Some clinical data have shown that glatiramer acetate (Copaxone), a synthetic amino acid polymer empirically found to suppress experimental allergic encephalomyelitis (EAE), an animal model of MS, might help improve the outcome of patients with multiple sclerosis (MS). We performed a Cochrane review of all randomised, placebo-controlled trials of glatiramer acetate in MS, whatever the disease course. We searched the Cochrane MS Group trials register (June 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2003), MEDLINE (PubMed) (January 1966 to June 2003), EMBASE (January 1988 to June 2003) and hand searching of symposia reports (1990-2002) from the neurological Associations and MS Societies in both Europe and America. All randomised controlled trials (RCTs) comparing glatiramer acetate and placebo in patients with definite MS, whatever the administration schedule and disease course, were eligible for this review. Both patients with relapsing-remitting (RR) and chronic progressive (CP) MS were analysed. Study protocols were comparable across trials as to patient entry criteria and outcome definition. No major flaws were found in methodological quality. However, efficacy of blinding should be balanced against well-known side effects, including injection-site reactions in glatiramer acetate-treated patients. A total of 646 patients contributed to this review, as it is summarised in Table 01. Glatiramer acetate did not show any significant effect on disease progression, measured as a sustained worsening in the Expanded Disability Status Scale (EDSS). On the other hand, a slight decrease in the mean EDSS score, driven by a major study, should be considered in the light of the limited validity of this outcome measure. No benefit was shown in CP MS patients (progression at two years: RR=0.69, 95% CI [0.33 to 1.46]). The frequency of reported adverse events does not support any major toxicity associated with glatiramer acetate administration. The most common systemic adverse event was a transient and self-limiting patterned reaction of flushing, chest tightness, sweating, palpitations, anxiety (relative risk = 3.40 (95% CI [2.22 to 5.21], p <0.00001]). Local injection-site reactions were observed in up to a half of patients treated with glatiramer acetate, thus making a blind assessment of outcomes questionable. Glatiramer acetate did not show any beneficial effect on the main outcome measures in MS, i.e. disease progression, and it does not substantially affect the risk of clinical relapses. Therefore its routine use in clinical practice is not currently supported. More investigations are needed. Further research should also develop more reliable measures of patient disability over time and include quality of life among primary outcomes.

Working memory deficits in multiple sclerosis: a controlled study with auditory P600 correlates

Background: Recently, the P600 component of event related potentials, a waveform that is conceived to be generated and/or modulated by basal ganglia and cingulate area has been considered an index...

Apoferritin Attenuates Experimental Allergic Encephalomyelitis in SJL Mice

Ferritin has been shown to attenuate iron-catalyzed oxidative damage in several experimental conditions. Since oxidative damage has been implicated in the pathogenesis of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), an animal model of MS, we tested the hypothesis that ferritin would act to attenuate disease. The experimental design was to increase plasma ferritin levels during the active stage of EAE by giving systemic injections of apoferritin and then compare disease activity between these mice and EAE mice administered vehicle. Additional mice received systemic injections of iron, which induces ferritin synthesis, in order to test the effects of exogenous iron on the disease course. Although plasma levels of ferritin were found to be elevated in both apoferritin and iron-injected EAE mice, only apoferritin treatment resulted in a reduction in disease activity compared to EAE mice given vehicle. The suppressive effects of apoferritin administration suggest that the increase in endogenous ferritin levels that have been previously observed in the cerebrospinal fluid of chronic progressive MS patients with active disease might be functioning to limit the severity and spread of tissue damage.

VP1 DNA sequences of JC and BK viruses detected in urine of systemic lupus erythematosus patients reveal no differences from strains expressed in normal individuals

The ubiquitous human polyomaviruses BK (BKV) and JC (JCV) persist with no adverse effects in immunocompetent individuals. Virus-induced pathogenesis has been linked to virus reactivation during impaired immune conditions. Previous studies have shown a significant difference between the VP1 DNA sequences of JCV obtained from control urine samples and those in progressive multifocal leukoencephalopathy brain samples. This difference could not be detected when comparing normal control urinary JCV DNA with DNA sequences from chronic progressive multiple sclerosis patients. Since BKV and JCV are readily activated in systemic lupus erythematosus (SLE) patients, the presence of specific strains, related to VP1 DNA sequences, was investigated in these patients. VP1 DNA sequences in 100 urine samples from 21 SLE patients and 75 urine samples from 75 healthy pregnant women were analysed and compared to previously reported sequences. The results show that the VP1 sequence profiles of JCV and BKV excreted by SLE patients do not differ significantly from those excreted by immunocompetent individuals. The European JCV subtypes 1A or 1B were represented among all JCV-positive urine specimens, while BKV VP1 sequences showed complete, or almost complete, identity with the MM or JL strains. Different urine samples from the same patient collected over a 1 year period were predominantly stable. BKV VP1 DNA in urine specimens from healthy pregnant women was only detected during the third trimester of their pregnancy. These results argue against SLE-specific JCV and BKV strains and suggest reactivation of the viruses rather than recurrent re-infections of patients with SLE.

Serial evoked potential studies and MRI imaging in chronic progressive multiple sclerosis.

Measurements of serial evoked potential latencies and plaque burden on MRI scans are often obtained during clinical studies of multiple sclerosis patients to provide additional information to the disability-based primary endpoints. The ideal laboratory-based marker of progression would be expected to significantly change over the time period of study. Serial visual (VEP) and brainstem auditory evoked potentials (BAEP) and MRI scans of 11 chronic progressive MS patients were obtained over a 1.5 year period in a clinical study. Over this period, there was no significant change in disability as measured by the Kurtzke EDSS, Ambulation Index or Neurological Rating Score. The VEP P100 significantly progressed over the period of study. However, the MRI T(2) plaque burden and BAEP I-V intrapeak latency did not significantly progress over the 1.5 years. We conclude that, in chronic progressive MS, serial visual evoked potential tests may complement standard disability-based endpoints to assess disease progression.

Ferritin, transferrin and iron concentrations in the cerebrospinal fluid of multiple sclerosis patients

The concentrations of ferritin, transferrin and iron were measured in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) and control patients. Ferritin levels were significantly elevated in the CSF of chronic progressive active MS patients (4.71±0.54 ng/ml) compared to levels in normal individuals (3.07±0.17 ng/ml). MS patients with active or stable relapsing–remitting disease had ferritin levels that were comparable to those found in normal individuals. There were no significant differences in transferrin or iron levels in the CSF between MS and normal individuals. Both ferritin and transferrin levels were elevated in patients that had high CSF IgG values but not in patients with a high IgG index. Since ferritin binds iron, the increase of CSF ferritin levels in chronic progressive MS patients could be a defense mechanism to protect against iron induced oxidative injury. Ferritin levels could be a laboratory measure that helps to distinguish between chronic progressive and relapsing–remitting MS.

Cytokine secretion of myelin basic protein reactive T cells in patients with multiple sclerosis

The objective of this study was to determine whether autoreactive T cells in patients with multiple sclerosis (MS) are polarized and committed in their differentiation to a stable cytokine phenotype or whether the cytokine secretion can be altered. We examined the cytokines secreted by myelin basic protein (MBP) as compared to tetanus toxoid-reactive (TT) T cells in 12 patients with relapsing remitting MS (RR-MS), 9 patients with chronic progressive MS (CP-MS), and 14 normal individuals. A total of 5094 short term T cell lines to MBP and TT were generated in the presence of growth conditions promoting Th1 (IL-12/ α–IL-4 mAb) or Th2 (IL-4/ α–IL-12 mAb) cytokine secretion. Antigen-specific cytokine secretion from normals and MS patients could be shifted to a Th1 or Th2 type phenotype depending upon culture conditions, indicating that the phenotype of MBP reactive T cells can be altered even in longstanding chronic progressive MS. There were no significant differences in the cytokine patterns secreted by MBP reactive T cells in patients with MS as compared to normal individuals. However, CP-MS patients tended to have fewer MBP reactive T cells secreting IL-4 when cultured with IL-12/anti-IL-4 mAb and more IFN- γ secreting MBP reactive T cells when cultured with IL-4/anti-IL-12 mAb as compared to both normal controls and RR-MS, suggesting that cells from these patients might be more polarized or that fewer undifferentiated MBP-reactive cells are present in these individuals. The most striking observation was that in contrast to the RR-MS patients and normal controls, almost none of the MBP reactive T cells secreting cytokines in CP-MS incorporated 3[ H] thymidine. This may be due to chronic in vivo stimulation in the presence of IL-12, or because these T cells may have entered a terminally differentiated state. Nonetheless, the ability to alter the cytokine secretion of autoreactive T cell lines even in longstanding autoimmune disease indicates that cytokine therapy might have therapeutic benefits by switching the function of myelin reactive T cells such that they are non-pathogenic.