Treatment of Multiple Sclerosis By Antigen Specific Tolerance Induction with Synthetic Peptide Mbp8298: Hla-Dr Specific Delay of Disease Progression in a Phase LI Clinical Study

2006 ◽  
Vol 119 ◽  
pp. S46
Author(s):  
Mark Krantz ◽  
Kenneth Warren ◽  
Ingrid Catz ◽  
Les Ferenczi
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Study ◽  
Disease Progression ◽  
Synthetic Peptide ◽  
Tolerance Induction ◽  
Hla Dr ◽  
Specific Tolerance

scholarly journals Antigen-Specific Immune Tolerance in Multiple Sclerosis—Promising Approaches and How to Bring Them to Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Andreas Lutterotti ◽  
Helen Hayward-Koennecke ◽  
Mireia Sospedra ◽  
Roland Martin
Keyword(s):  
Multiple Sclerosis ◽  
Patient Selection ◽  
Tolerance Induction ◽  
Mechanisms Of Action ◽  
Clinical Development ◽  
Clinical Testing ◽  
Development Path ◽  
Conventional Drug ◽  
Key Aspects ◽  
Specific Tolerance

Antigen-specific tolerance induction aims at treating multiple sclerosis (MS) at the root of its pathogenesis and has the prospect of personalization. Several promising tolerization approaches using different technologies and modes of action have already advanced to clinical testing. The prerequisites for successful tolerance induction include the knowledge of target antigens, core pathomechanisms, and how to pursue a clinical development path that is distinct from conventional drug development. Key aspects including patient selection, outcome measures, demonstrating the mechanisms of action as well as the positioning in the rapidly growing spectrum of MS treatments have to be considered to bring this therapy to patients.

scholarly journals Clinical Sub-Groups of Multiple Sclerosis in Relation to HLA: DR Alleles as Possible Markers of Disease Progression

1985 ◽  
Vol 12 (2) ◽  
pp. 106-110 ◽  
Author(s):  
Pierre Duquette ◽  
Francine Décary ◽  
Juliana Pleines ◽  
Denise Boivin ◽  
Gilles Lamoureux ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Hla Antigens ◽  
Clinical Criteria ◽  
Hla Dr ◽  
Hla Dr3

ABSTRACT:We have examined the distribution of HLA antigens in 70 multiple sclerosis (MS) patients divided in three groups defined according to clinical criteria: benign MS, severe MS, cerebellar MS. We have found a significant association between severe MS and HLA-DR2, and between benign MS of more than 15 years of evolution and HLA-DR3. We review previous work along the same line and conclude that the association of HLA antigens with “clinical subgroups of MS” could indicate a genetically based heterogeneity of the disease and offer help in establishing a prognosis.

scholarly journals Antigen-specific tolerization in human autoimmunity: Inhibition of interferon-beta1a anti-drug antibodies in multiple sclerosis

2021 ◽  
Author(s):  
Monica Marta ◽  
David Baker ◽  
Paul Creeke ◽  
Gareth Pryce ◽  
Sharmilee Gnanapavan ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Tolerance Induction ◽  
Neutralizing Antibody ◽  
Immune Tolerance Induction ◽  
Autoimmune Condition ◽  
Potential Risks ◽  
Treatment Alternatives ◽  
Specific Tolerance

ABSTRACTBackgroundAntigen-specific tolerance in auto-immune diseases is the goal for effective treatment with minimal side-effects. Whilst this is achievable in animal models, notably via intravenous delivery of the model-specific autoantigen following transient CD4 T cell depletion, specific multiple sclerosis autoantigens remain unproven. However, anti-drug antibodies to human therapeutic proteins represent a model human autoimmune condition, which may be used to examine immune-tolerance induction. Some people with MS (PwMS) on interferon-beta1a (IFNβ1a) develop neutralizing antibodies to IFNβ1a that do not disappear in repeated tests over years.MethodsOne PwMS was recruited, as part of a planned phase IIa trial (n=15), who had developed neutralizing antibodies to subcutaneous IFNβ1a. Mitoxantrone (12mg/m2) was administered as a lymphocyte depleting agent followed by four days of (88μg/day + three 132μg/day) intravenous IFNβ1a. Subcutaneous IFNβ1a three times a week was maintained during follow-up. IFNβ1a neutralizing antibody responses in serum were measured during treatment and three-monthly for 12 months.FindingsOne participant was recruited and, within 6 months of tolerization, the neutralizing antibodies were undetectable. The tolerization treatment was well tolerated. However, the study was terminated after the first enrolment, on ethical grounds, as treatment alternatives became available and the potential risks of mitoxantrone use increased.InterpretationThe data suggest that it may be possible to induce antigen-specific tolerance by providing tolerogenic antigen following transient immune depletion. Further studies are warranted.FundingThe study was supported by an unrestricted research grant from Merck-Serono.

scholarly journals Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Lina Samira Bahr ◽  
Markus Bock ◽  
Daniela Liebscher ◽  
Judith Bellmann-Strobl ◽  
Liane Franz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Study ◽  
Disease Progression ◽  
Clinical Evidence ◽  
Controlled Study ◽  
Intermittent Fasting ◽  
Therapeutic Effects ◽  
Randomized Controlled ◽  
Markers Of Inflammation ◽  
Ketogenic Diets

Abstract Background Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting diets (FDs) and ketogenic diets (KDs) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KDs and FDs on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate whether a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression. Methods This study is a single-center, randomized, controlled, parallel-group study. One hundred and eleven patients with relapsing–remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three 18-month dietary interventions: a KD with a restricted carbohydrate intake of 20–40 g/day; a FD with a 7-day fast every 6 months and 14-h daily intermittent fasting in between; and a fat-modified SD as recommended by the German Nutrition Society. The primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed. Discussion Preclinical data suggest that a KD and a FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and a FD on disease progression of MS. Trial registration ClinicalTrials.gov, NCT03508414. Retrospectively registered on 25 April 2018.

scholarly journals Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study

2019 ◽  
Author(s):  
Lina Samira Bahr ◽  
Markus Bock ◽  
Daniela Liebscher ◽  
Judith Bellmann-Strobl ◽  
Liane Franz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Study ◽  
Disease Progression ◽  
Clinical Evidence ◽  
Controlled Study ◽  
Intermittent Fasting ◽  
Therapeutic Effects ◽  
Dietary Interventions ◽  
Randomized Controlled ◽  
Markers Of Inflammation

Abstract Background: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting (FD) and ketogenic diets (KD) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KD and FD on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate if a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression. Methods: This study is a single-center, randomized, controlled, parallel-group study. One hundred and eleven patients with relapsing-remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three 18-month dietary interventions. The dietary interventions are 1) a KD with a restricted carbohydrate intake of 20-40 g/day, 2) a FD with a 7 day fast every 6 months and 14 hours daily intermittent fasting in between, and 3) a fat-modified SD as recommended by the German Nutrition Society. The primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed. Discussion: Preclinical data suggest that KD and FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and FD on disease progression of MS. Trial Registration: ClinicalTrials.gov; NCT03508414; Registered 25 April 2018, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03508414

scholarly journals Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study

2019 ◽  
Author(s):  
Lina Samira Bahr ◽  
Markus Bock ◽  
Daniela Liebscher ◽  
Judith Bellmann-Strobl ◽  
Liane Franz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Study ◽  
Disease Progression ◽  
Clinical Evidence ◽  
Controlled Study ◽  
Intermittent Fasting ◽  
Therapeutic Effects ◽  
Dietary Interventions ◽  
Randomized Controlled ◽  
Markers Of Inflammation

Abstract Background Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting (FD) and ketogenic diets (KD) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KD and FD on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate if a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression. Methods This study is a single-center, randomized, controlled, parallel-group study. One hundred eleven patients with relapsing-remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three dietary interventions over 18 months. Dietary interventions are 1) a KD with a carbohydrate intake of 20-40 g/day, 2) a FD with 7 days of fasting every 6 months and 14 hours intermittent fasting daily in between, and 3) a fat-modified SD as recommended by the German Nutrition Society. Primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed. Discussion Preclinical data suggest that KD and FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and FD on disease progression of MS. Trial Registration ClinicalTrials.gov; NCT03508414; Registered 25 April 2018, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03508414

Predictive value of clinical and MRI parameters for disease progression in multiple sclerosis – a longitudinal retrospective study

2009 ◽  
Vol 36 (S 02) ◽  
Author(s):  
A Hahn ◽  
T Schmidt-Wilcke ◽  
S Prügl ◽  
G Schuierer ◽  
U Bogdahn ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Retrospective Study ◽  
Disease Progression ◽  
Predictive Value
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