scholarly journals Therapeutic Value of Single Nucleotide Polymorphisms on the Efficacy of New Therapies in Patients with Multiple Sclerosis

2021 ◽  
Vol 11 (5) ◽  
pp. 335
Author(s):  
María José Zarzuelo Romero ◽  
Cristina Pérez Ramírez ◽  
María Isabel Carrasco Campos ◽  
Almudena Sánchez Martín ◽  
Miguel Ángel Calleja Hernández ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mechanism Of Action ◽  
Dimethyl Fumarate ◽  
Response To Treatment ◽  
Nucleotide Polymorphisms ◽  
New Therapies ◽  
Therapeutic Value ◽  
The Impact

The introduction of new therapies for the treatment of multiple sclerosis (MS) is a very recent phenomenon and little is known of their mechanism of action. Moreover, the response is subject to interindividual variability and may be affected by genetic factors, such as polymorphisms in the genes implicated in the pathologic environment, pharmacodynamics, and metabolism of the disease or in the mechanism of action of the medications, influencing the effectiveness of these therapies. This review evaluates the impact of pharmacogenetics on the response to treatment with new therapies in patients diagnosed with MS. The results suggest that polymorphisms detected in the GSTP1, ITGA4, NQO1, AKT1, and GP6 genes, for treatment with natalizumab, ZMIZ1, for fingolimod and dimethyl fumarate, ADA, for cladribine, and NOX3, for dimethyl fumarate, may be used in the future as predictive markers of treatment response to new therapies in MS patients. However, there are few existing studies and their samples are small, making it difficult to generalize the role of these genes in treatment with new therapies. Studies with larger sample sizes and longer follow-up are therefore needed to confirm the results of these studies.

CD46 in a Spanish cohort of multiple sclerosis patients: genetics, mRNA expression and response to interferon-beta treatment

2010 ◽  
Vol 17 (5) ◽  
pp. 513-520 ◽  
Author(s):  
Roberto Alvarez-Lafuente ◽  
Fiona Blanco-Kelly ◽  
Marta Garcia-Montojo ◽  
Alfonso Martínez ◽  
Virginia De Las Heras ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mrna Expression ◽  
Interferon Beta ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Multiple Sclerosis Patients ◽  
Spanish Cohort ◽  
Independent Cohort

Background: In a prior study of our group we found an up-regulation of CD46 expression in a cohort of Spanish multiple sclerosis (MS) patients. Objective: To evaluate the potential role of CD46 in the response to interferon-beta treatment in MS patients through the analysis of five tagging single nucleotide polymorphisms (SNPs) and measurement of mRNA. Methods: A total of 406 MS patients and 513 control patients were analysed for five SNPs at the CD46 locus. Furthermore, 163 MS patients and 163 matched control patients were analysed by RT-PCR for the CD46 mRNA expression in three blood samples (basal, and at 6 and 12 months of interferon-beta treatment) collected in the course of a 1-year follow-up. Results: Two genotypes of rs2724385 polymorphism (AT and TT) could be markers of response to interferon-beta therapy in MS patients ( p = 0.007 and p = 0.006, respectively). Furthermore, the frequency of interferon-beta responders was 44.4% (32/72) in MS patients with an increased CD46 mRNA expression, vs. 65.9% (60/91) in patients with a decreased CD46 mRNA expression ( p = 0.006). Conclusion: The present study shows that CD46 could be associated with the response to interferon-beta therapy; however, the genetic results should be replicated in an independent cohort and further studies are needed to confirm the role of CD46.

scholarly journals Adipsin Is Associated with Multiple Sclerosis: A Follow-Up Study of Adipokines

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Renuka Natarajan ◽  
Sanna Hagman ◽  
Mari Hämälainen ◽  
Tiina Leppänen ◽  
Prasun Dastidar ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Responses ◽  
Clinically Isolated Syndrome ◽  
Follow Up Study ◽  
Disease Characteristics ◽  
Group A ◽  
Edss Score ◽  
The Impact

Background and Objective. The role of adipokines in regulation of immune responses has been recognized, but very little is known about their impact on multiple sclerosis (MS). In this study, we analysed whether the major adipokines are differentially expressed in plasma of patients with different MS subtypes and clinically isolated syndrome (CIS) and explored their association with major disease characteristics.Methods. The levels of adiponectin, adipsin, leptin, and resistin in the plasma of 80 patients with different subtypes of MS and CIS were followed up annually over the two years. The data obtained were correlated with disease activity, EDSS and volumes of T1-weighted lesions (T1-LV), and fluid attenuation inversion recovery lesions (FLAIR-LV) on MRI.Results. In MS group, a correlation was found between the level of adipsin and EDSS score at baseline (r=0.506,p<0.001). In RRMS, the levels of adipsin correlated with EDSS scores (r=0.542,p=0.002), T1-LV (r=0.410,p=0.034), and FLAIR-LV (r=0.601,p=0.0001) at baseline and an increase in the T1-LV over the follow-up (r=0.582,p=0.003). Associations with other adipokines were not detected.Conclusion. Our exploratory study provides novel insights on the impact of adipokines in MS and suggests that adipsin exerts predictive potential as a biomarker of neurodegeneration.

scholarly journals POS0677 THE ROLE OF MUSCULOSKELETAL ULTRASOUND IN PREDICTING THE RESPONSE TO JAK INHIBITORS: RESULTS FROM A LARGE MONOCENTRIC COHORT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 583-583
Author(s):  
C. Garufi ◽  
F. Ceccarelli ◽  
F. R. Spinelli ◽  
S. Mancuso ◽  
C. Pirone ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Structural Damage ◽  
Power Doppler ◽  
Response To Treatment ◽  
Jak Inhibitors ◽  
Inflammatory Score ◽  
Inflammatory Status

Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos

scholarly journals Impact of COVID-19 on multiple sclerosis care and management: Results from the European Committee for Treatment and Research in Multiple Sclerosis survey

2021 ◽  
pp. 135245852110053
Author(s):  
Emilio Portaccio ◽  
Mattia Fonderico ◽  
Bernhard Hemmer ◽  
Tobias Derfuss ◽  
Bruno Stankoff ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Access To Care ◽  
Online Survey ◽  
Dimethyl Fumarate ◽  
Standards Of Care ◽  
Treatment Practices ◽  
European Committee ◽  
Disease Modifying Therapy ◽  
Anti Cd20 ◽  
The Impact

Background: The spread of Coronavirus disease-19 (COVID-19) poses unique challenges in the management of people with multiple sclerosis (PwMS). Objectives: To collect data about the impact of COVID-19 emergency on access to care for PwMS and on MS treatment practices. Methods: Between March and July 2020, the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) promoted an online survey covering patient access to care, management of relapses and visits, disease-modifying therapy (DMT) and experience with COVID-19. Results: Three-hundred and sixty neurologists from 52 countries (68% from Europe) completed the survey. 98% reported COVID-19-related restrictions. Telemedicine was adopted to overcome the limited access to care and was newly activated (73%) or widely implemented (17%). 70% reported changes in DMT management. Interferons and glatiramer were considered safe. Dimethyl fumarate, teriflunomide and fingolimod were considered safe except for patients developing lymphopenia. No modifications were considered for natalizumab in 64%, cladribine in 24%, anti-CD20 in 22% and alemtuzumab in 17%; 18% (for alemtuzumab and cladribine) and 43% (for anti-CD20) considered postponing treatment. Conclusion: The ECTRIMS survey highlighted the challenges in keeping standards of care in clinical practice. Telemedicine clearly needs to be implemented. Gathering data on DMT safety will remain crucial to inform treatment decisions.

scholarly journals JC Virus Seroprevalence and JCVAb Index in Polish Multiple Sclerosis Patients Treated with Immunomodulating or Immunosuppressive Therapies

2021 ◽  
Vol 10 (9) ◽  
pp. 1998
Author(s):  
Robert Bonek ◽  
Wojciech Guenter ◽  
Robert Jałowiński ◽  
Anna Karbicka ◽  
Anna Litwin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Jc Virus ◽  
Dimethyl Fumarate ◽  
Risk Category ◽  
Seroprevalence Rate ◽  
Immunomodulatory Drugs ◽  
Cross Sectional ◽  
Treatment Type ◽  
Multiple Sclerosis Patients ◽  
The Impact

The use of a highly-effective treatment for multiple sclerosis (MS) is associated with a severe risk of developing complications, such as progressive multifocal leukoencephalopathy (PML) caused by the John Cunningham virus (JCV). The aim of this study was to evaluate the correlation between anti-JCV Ab seroprevalence, anti-JCV AI, demographic and clinical factors as well as the type of therapy used in the Polish MS population. This is a multicentre, prospective and cross-sectional study involving 1405 MS patients. The seroprevalence of anti-JCV Ab and anti-JCV AI levels as well as AI categories were analysed with the use of a second-generation two-step ELISA test (STRATIFY JCV DxSelect). The overall prevalence of anti-JCV Ab was 65.8%. It was shown that seroprevalence increases with the patient’s age. The seroprevalence was significantly associated with the treatment type, and the highest values (76%) were obtained from immunosuppressant-treated patients. Overall, 63.3% of seropositive patients had an antibody index (AI) level of >1.5. In the seropositive patient group, the mean AI level amounted to 2.09. Similarly to the seroprevalence, AI levels correlated with the patient’s age; AI level for patients above 40 years old and from subsequent age quintiles plateaued, amounting to at least 1.55. Patients treated with immunosuppressants and immunomodulatory drugs obtained the highest (1.67) and lowest (1.35) AI levels, respectively. Of the immunosuppressants used, the highest mean AI levels were observed in mitoxantrone and cladribine groups, amounting to 1.75 and 1.69, respectively. In patients treated with immunomodulatory drugs, the lowest AI levels were observed in the dimethyl fumarate (DMF) group (1.11). The seroprevalence rate in the Polish MS population is one of the highest in Europe. The majority of seropositive patients had an anti-JCV Ab level qualifying them for a high-risk category. The highest mean AI levels are observed in patients receiving immunosuppressants, especially mitoxantrone and cladribine. Patients receiving immunomodulatory drugs have lower AI levels compared to treatment-naïve subjects, especially when treated with DMF. Further studies, especially longitudinal studies, are required to determine the impact of MS drugs on the seroprevalence of anti-JCV Ab and AI levels.

scholarly journals Rural or urban living and Parkinson's disease

1996 ◽  
Vol 54 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Henrique B. Ferraz ◽  
Luiz A. F. Andrade ◽  
Vítor Tumas ◽  
Leandro C. Calia ◽  
Vanderci Borges
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rural Area ◽  
Living Environment ◽  
Response To Treatment ◽  
Urban Group ◽  
Determining Factor ◽  
Rural Group

Although the precise etiology of Parkinson's disease (PD) is as yet unknown, it appears that certain environmental factors are involved. Prior living in a rural area has been implicated as a possible risk factor for PD, particularly in the early onset type. We evaluated the role of previous living conditions in the clinical correlates and outcome characteristics of 118 PD patients. All of them were seen from January 1987 to October 1992. The Rural Group (RG) comprised 71 patients (60.2%) who had lived in the rural area for at least 10 years (mainly in early phase of life) and the Urban Group (UG) consisted of 47 patients (39.8%) who had lived their entire life in an urban environment. The average age at the beginning of the symptoms was 58.8 in the RG and 54.1 in the UG. The mixed form of the disease (tremor, rigidity and akinesia) was the most frequent in both groups. A minimum 6-month follow-up period was undertaken with 63 patients (average 20 months) and no difference in response to treatment or in progression of the illness was detected between the two groups. Our data show that the previous living environment does not appear to be a determining factor in either the clinical or outcome characteristics of PD.

scholarly journals Use of newer disease-modifying therapies in pediatric multiple sclerosis in the US

Neurology ◽  
2018 ◽  
Vol 91 (19) ◽  
pp. e1778-e1787 ◽  
Author(s):  
Kristen M. Krysko ◽  
Jennifer Graves ◽  
Mary Rensel ◽  
Bianca Weinstock-Guttman ◽  
Gregory Aaen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Side Effect ◽  
Pediatric Patients ◽  
Dimethyl Fumarate ◽  
Short Term ◽  
Pediatric Multiple Sclerosis ◽  
Disease Modifying Therapies ◽  
The Us ◽  
Disease Modifying

ObjectiveTo characterize the use and safety of newer disease-modifying therapies (DMTs) in children with multiple sclerosis (MS) and clinically isolated syndrome (CIS) treated under 18 years of age.MethodsThis is a cohort study including children with MS or CIS followed at 12 outpatient practices participating in the US Network of Pediatric MS Centers. DMT use, including duration, dose, and side effects, was analyzed. Newer DMTs were defined as agents receiving Food and Drug Administration approval or with increased use in adult MS after 2005.ResultsAs of July 2017, 1,019 pediatric patients with MS (n = 748) or CIS (n = 271) were enrolled (65% female, mean onset 13.0 ± 3.9 years, mean follow-up 3.5 ± 3.1 years, median 1.6 visits per year). Of these, 78% (n = 587) with MS and 11% (n = 31) with CIS received DMT before 18 years of age. This consisted of at least one newer DMT in 42%, including dimethyl fumarate (n = 102), natalizumab (n = 101), rituximab (n = 57), fingolimod (n = 37), daclizumab (n = 5), and teriflunomide (n = 3). Among 17%, the initial DMT prescribed was a newer agent (36 dimethyl fumarate, 30 natalizumab, 22 rituximab, 14 fingolimod, 2 teriflunomide). Over the last 10 years, the use of newer agents has increased, particularly in those ≥12 years and to lesser extent in those <12 years. The short-term side effect profiles of newer DMTs did not differ from those reported in adults.ConclusionNewer DMTs are often used in pediatric MS, and have similar short-term safety, tolerability, and side effect profiles as in adults. These findings may help inform pediatric MS management.

scholarly journals The Ala/Ala genotype of PPARY Pro12 Ala polymorphism is associated with late onset of multiple sclerosis

2013 ◽  
Vol 65 (2) ◽  
pp. 447-453
Author(s):  
N. Lukic ◽  
A. Stankovic ◽  
E. Dincic ◽  
M. Bundalo ◽  
Z. Krsmanovic ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Late Onset ◽  
Age At Onset ◽  
Peroxisome Proliferator ◽  
Pro12ala Polymorphism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Post Hoc ◽  
Genotype And Allele Frequencies

The function of peroxisome proliferator-activated receptor ? (PPAR?) in immune regulation, as well as in antiinflammatory and anti-proliferative actions towards T lymphocytes, has been reported. A potential role of PPARs in multiple sclerosis (MS) was suggested. The aim of this study was to investigate if there is an association of PPAR?-2 Pro12Ala polymorphism with MS in 361 patients from Serbia. The genotype and allele frequencies of Pro12Ala polymorphism were not significantly different between controls and patients, or between females and males. In contrast to controls, we detected a rare Ala/Ala genotype in patients with MS. We found that there is a significant association of Ala/Ala genotype with older age at onset (ANOVA, p=0.07; LSD post-hoc, Ala/Ala vs. Pro/Ala, p=0.03, Ala/Ala vs. Pro/Pro p=0.02). It would be useful to validate our results in other populations, as well as to perform follow-up of the disease progression in regard to PPAR? genotypes.

Cognitive reserve moderates the impact of subcortical gray matter atrophy on neuropsychological status in multiple sclerosis

2015 ◽  
Vol 22 (1) ◽  
pp. 36-42 ◽  
Author(s):  
Claire M Modica ◽  
Niels Bergsland ◽  
Michael G Dwyer ◽  
Deepa P Ramasamy ◽  
Ellen Carl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Decline ◽  
Cognitive Processing ◽  
Gray Matter ◽  
Cognitive Reserve ◽  
Cognitive Outcome ◽  
Brain Reserve ◽  
The Impact ◽  
Normal Controls

Background: Cognitive decline is characterized in multiple sclerosis (MS), but the rate and severity vary. The reserve hypothesis proposes that baseline neurological differences impact cognitive outcome in neurodegenerative disease. Objective: To elucidate how brain reserve and cognitive reserve influence subcortical gray matter (SCGM) atrophy and cognitive decline in MS over 3 years. Methods: Seventy-one MS patients and 23 normal controls underwent magnetic resonance imaging and cognitive assessment at baseline and 3-year follow-up. The influence of reserve on cognitive processing speed (CPS) and memory was examined. Results: SCGM volume and cognitive scores were lower in MS than normal controls ( P⩽0.001). Accounting for baseline, comparison of follow-up means yielded a difference between groups in SCGM volume ( P<0.001) but not cognition (NS). Cognitive reserve ( P=0.005), but not brain reserve, contributed to CPS, with only low cognitive reserve MS subjects showing decline in CPS ( P=0.029). SCGM change predicted CPS outcome in MS with low cognitive reserve ( P=0.002) but not high cognitive reserve. There were no effects in the domain of memory. Conclusions: SCGM atrophy occurs in normal controls, but significantly more so in MS. While CPS did not change in normal controls, low cognitive reserve was associated with CPS decline in MS. High cognitive reserve protect MS patients from cognitive decline related to SCGM atrophy.

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