Article
Immunology
Igal Rosenstein, Sofia Rasch, Markus Axelsson, Lenka Novakova, Kaj Blennow, Henrik Zetterberg, Jan Lycke
Summary: This study suggests that determination of intrathecal immunoglobulin M synthesis (ITMS) and neurofilament light concentration in cerebrospinal fluid (CSF) can be useful biomarkers for predicting disease severity and disability in relapsing-remitting multiple sclerosis (RRMS). The combination of ITMS with CSF neurofilament light (cNfL) shows a stronger predictive value.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Clinical Neurology
Josephine Wauschkuhn, Gilberto Solorza Buenrostro, Lilian Aly, Susanna Asseyer, Rebecca Wicklein, Julia Maria Hartberger, Klemens Ruprecht, Mark Muehlau, Tanja Schmitz-Huebsch, Claudia Chien, Achim Berthele, Alexander U. U. Brandt, Thomas Korn, Friedemann Paul, Bernhard Hemmer, Hanna G. G. Zimmermann, Benjamin Knier
Summary: Thinning of retinal combined ganglion cell and inner plexiform layer (GCIP) as measured by OCT is common in patients with multiple sclerosis. This study aimed to investigate whether a single retinal OCT analysis allows prediction of future disease activity after a first demyelinating event. The results showed that GCIP thickness measurement provides information for early risk stratification and progression of multiple sclerosis after the initial manifestation.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Anna Bizon, Justyna Chojdak-Lukasiewicz, Slawomir Budrewicz, Anna Pokryszko-Dragan, Agnieszka Piwowar
Summary: This study aimed to investigate the alterations in the antioxidant balance in patients with RRMS and the factors influencing it. The study included 161 patients and 29 healthy individuals, and measured the activity of SOD, GPx, and CAT, as well as the concentration of IL-6, LPO, TOS, and TAS. The results showed decreased GPx activity and increased CAT activity in patients with RRMS compared to the control group, and these activities were influenced by gender and disease-modifying therapies. The findings suggest that enhancing GPx activity may be a potential therapeutic strategy for mitigating oxidative stress in RRMS.
Article
Biochemistry & Molecular Biology
Damien D. Pearse, Andrew B. Hefley, Alejo A. Morales, Mousumi Ghosh
Summary: This study investigated the expression of transglutaminase-2 (TG2) in brain tissue of multiple sclerosis (MS) patients and its correlation with binding partners and effectors involved in inflammation, scar formation, and repair antagonism. The results showed that TG2 was upregulated in active lesions and colocalized with astrocytes and extracellular matrix components.
Article
Immunology
Emanuele D'Amico, Aurora Zanghi, Nunziatina Laura Parrinello, Alessandra Romano, Giuseppe Alberto Palumbo, Clara Grazia Chisari, Simona Toscano, Francesco Di Raimondo, Mario Zappia, Francesco Patti
Summary: This study characterized the immune cell phenotypes of patients recently diagnosed with relapsing-remitting multiple sclerosis who had not received disease-modifying therapies. The results revealed differences in myeloid, B, and T cells between these patients and healthy controls.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Clinical Neurology
Pablo Rodriguez de Vera Gomez, Mariola Mendez Muros, Alberto Torres Cuadro, Francisco Javier Toyos Saenz de Miera, Rocio Lopez Ruiz, Raquel Guerrero Vazquez, Juan Jesus Garcia Gonzalez, Antonio Manuel Garrido Hermosilla, Tomas Martin Hernandez
Summary: This study describes the clinical and biochemical characteristics of GD-ALZ and the clinical course of GO-ALZ cases in patients treated with Alemtuzumab for RRMS. GD-ALZ was observed in 32.6% of the cases, mainly affecting women with an average age of 41.9 years. Having first-degree relatives with hypothyroidism was identified as a risk factor. GO-ALZ was diagnosed in 13.6% of the cases, with 3 cases requiring anti-IL-6 treatment.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Igal Rosenstein, Markus Axelsson, Lenka Novakova, Clas Malmestroem, Kaj Blennow, Henrik Zetterberg, Jan Lycke
Summary: While KFLC index is a useful diagnostic biomarker in multiple sclerosis (MS), its prognostic properties are less explored. This study found that high baseline KFLC index is predictive of PIRA, evidence of disease activity (EDA-3), and overall worse prognosis in MS.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Pablo Arroyo Pereiro, Albert Munoz-Vendrell, Isabel Leon Moreno, Laura Bau, Elisabet Matas, Lucia Romero-Pinel, Antonio Martinez Yelamos, Sergio Martinez Yelamos, Pol Andres-Benito
Summary: This study investigates the potential role of serum biomarkers in long-term prognostication of multiple sclerosis, and suggests that serum neurofilament light chain levels may serve as a promising marker for long-term disability.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Zhizheng Zhuo, Yongmei Li, Yunyun Duan, Guanmei Cao, Fenglian Zheng, Jinli Ding, Decai Tian, Xinli Wang, Jinhui Wang, Xinghu Zhang, Kuncheng Li, Fuqing Zhou, Muhua Huang, Yuxin Li, Haiqing Li, Chun Zeng, Ningnannan Zhang, Jie Sun, Chunshui Yu, Xuemei Han, Sven Haller, Frederik Barkhof, Fudong Shi, Yaou Liu
Summary: Three MRI subtypes of RRMS were identified with distinct clinical and imaging features and different prognoses. The subtypes showed variations in cognitive impairment and conversion rate to SPMS.
JOURNAL OF NEUROLOGY
(2021)
Article
Immunology
Britta E. Jones, Megan D. Maerz, Henry T. Bahnson, Ashwin Somasundaram, Lucas H. McCarthy, Cate Speake, Jane H. Buckner
Summary: The coinhibitory receptor LAG-3 plays a role in regulating T cell activation and proliferation, and its low expression is associated with altered T cell function and resistance to cell death in subjects with RRMS. Dysregulation of LAG-3 expression persists after T cell stimulation, suggesting its potential as a target for autoimmune disease treatment.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Insha Zahoor, Hamid Suhail, Indrani Datta, Mohammad Ejaz Ahmed, Laila M. Poisson, Jeffrey Waters, Faraz Rashid, Rui Bin, Jaspreet Singh, Mirela Cerghet, Ashok Kumar, Md Nasrul Hoda, Ramandeep Rattan, Ashutosh K. Mangalam, Shailendra Giri
Summary: Metabolic aberrations were found to impact the pathogenesis of relapsing-remitting multiple sclerosis, with changes in multiple metabolic pathways identified in patient samples. Enhanced glycolysis in immune cells of MS patients was observed, and treatment with a glycolytic inhibitor showed promising effects in ameliorating disease progression by promoting an antiinflammatory phenotype. This study highlights the potential of blood-based metabolomic approaches in identifying therapeutic targets for developing new treatment strategies for multiple sclerosis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Tatiana Koudriavtseva, Svetlana Lorenzano, Maria Cellerino, Mauro Truglio, Marco Fiorelli, Caterina Lapucci, Giovanna D'Agosto, Laura Conti, Annunziata Stefanile, Silvana Zannino, Maria Maddalena Filippi, Antonio Cortese, Carlo Piantadosi, Marta Maschio, Andrea Maialetti, Edvina Galie, Marco Salvetti, Matilde Inglese
Summary: The objective of this observational study was to identify the most specific pro-coagulative/vascular factors for multiple sclerosis pathogenesis and to correlate them with brain hemodynamic abnormalities. The results showed that tissue-factor was one of the key variables in differentiating multiple sclerosis from controls and relapse from remission.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Clinical Neurology
Rita Rodrigues, Raquel Rocha, Goncalo Bonifacio, Daniela Ferro, Francisco Sabenca, Ana Isabel Goncalves, Filipe Correia, Joaquim Pinheiro, Jose Leal Loureiro, Rui Pedro Guerreiro, Jose Vale, Maria Jose Sa, Andreia Costa
Summary: Therapeutic inertia (TI) is a common issue in the management of RRMS patients in Portugal, with approximately 1 in 5 patients exhibiting TI. Factors such as absence of relapses, current use of disease-modifying therapies (DMT), absence of adverse events, and care level of the treatment center are associated with TI. Further studies are needed to explore the impact of these factors on therapeutic decisions in RRMS patients.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2021)
Article
Clinical Neurology
Malin Boremalm, Peter Sundstrom, Jonatan Salzer
Summary: Rituximab is safe and effective in treating RRMS, with long-term effects on inflammatory disease activity. Disease reactivation is rare in MS patients who discontinued treatment, and low-dose rituximab (< 1000 mg yearly) is sufficient to maintain suppression of inflammatory disease activity in stable patients.
JOURNAL OF NEUROLOGY
(2021)
Article
Immunology
Nicole Kashani, Eve E. Kelland, Borna Vajdi, Lauren M. Anderson, Wendy Gilmore, Brett T. Lund
Summary: This study revealed that patients treated with alemtuzumab for multiple sclerosis showed an increase in the number and function of regulatory B cells after treatment, which were positively correlated with regulatory T cells. Additionally, an anti-inflammatory bias in monocytes was observed after the second annual course of treatment. These findings highlight the importance of further studies on all regulatory cell types following alemtuzumab treatment to understand the mechanisms of drug action and identify key predictors of durable clinical efficacy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
Andreas Hoeflich, Brit Fitzner, Christina Walz, Michael Hecker, Armin Tuchscherer, Julia Brenmoehl, Uwe Klaus Zettl
Summary: The study investigated the IGF system in MS patients during TCA treatment, finding that IGF-I levels increased in serum while fragmentation of IGFBP-2 and IGFBP-3 decreased in CSF. The reduction in IGFBP fragmentation and lower ratio of IGF-II to intact IGFBPs indicate a regulation of IGF-II bioactivity in CSF during repeated intrathecal TCA administration in MS patients.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Neurosciences
Michael Hecker, Brit Fitzner, Kathrin Jaeger, Jan Buehring, Margit Schwartz, Alexander Hartmann, Michael Walter, Uwe Klaus Zettl
Summary: This study found that telomere length in MS patients is associated with disease progression and patient type. The RRMS group had significantly shorter relative LTL, and shorter telomeres at baseline were associated with a higher conversion rate to SPMS in RRMS patients. The LTL decrease over time was similar in RRMS and PPMS patients.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Elena Putscher, Michael Hecker, Brit Fitzner, Peter Lorenz, Uwe Klaus Zettl
Summary: Splicing is a crucial RNA processing step, with genetic variations playing a role in altering this process and contributing to the development of diseases. The splicing pattern can be examined through gene expression analyses, computational tools, and splicing reporter minigene assays. These assays, like pDESTsplice and pSpliceExpress, offer a way to study alternative splicing events and understand disease mechanisms better.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Niklas Frahm, Michael Hecker, Uwe Klaus Zettl
Summary: Polypharmacy is common among elderly and chronically ill patients, especially those with dementia, PD, or MS. The main predictor of polypharmacy is the complex symptom profile of these neurological disorders. Negative impacts associated with polypharmacy include potentially inappropriate medication, drug-drug interactions, and poor quality of life.
CURRENT PHARMACEUTICAL DESIGN
(2021)
Article
Medicine, General & Internal
Michael Hecker, Brit Fitzner, Elena Putscher, Margit Schwartz, Alexander Winkelmann, Stefanie Meister, Ales Dudesek, Dirk Koczan, Peter Lorenz, Nina Boxberger, Uwe Klaus Zettl
Summary: This study found that MS-associated SNPs can affect the expression of mature miRNAs and provided insights into the dysregulation of miRNAs in MS. Further studies on the maturation and function of miRNAs in different cell types and tissues may help to gain a more detailed functional understanding of the genetic basis of MS.
Article
Pharmacology & Pharmacy
Paula Bachmann, Niklas Frahm, Jane Louisa Debus, Pegah Mashhadiakbar, Silvan Elias Langhorst, Barbara Streckenbach, Julia Baldt, Felicita Heidler, Michael Hecker, Uwe Klaus Zettl
Summary: Polypharmacy is a common problem in modern medicine, especially among patients with chronic diseases such as multiple sclerosis. This study aimed to assess the prevalence and clinical relevance of polypharmacy and potential drug-drug interactions (pDDIs) in multiple sclerosis patients. The findings revealed that the majority of patients had polypharmacy and at least one pDDI.
Article
Health Care Sciences & Services
Silvan Elias Langhorst, Niklas Frahm, Michael Hecker, Pegah Mashhadiakbar, Barbara Streckenbach, Julia Baldt, Felicita Heidler, Uwe Klaus Zettl
Summary: This study investigated the vaccination status, vaccination card knowledge, and vaccination behavior of multiple sclerosis (MS) patients. The results showed that the vaccination coverage for tetanus, diphtheria, pertussis, and poliomyelitis was relatively high, but there were some patients with incomplete vaccination or incorrect self-reported vaccination status. Patients who did not have regular vaccination card checks were more likely to be male and had lower knowledge and willingness regarding vaccination.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Michael Hecker, Niklas Frahm, Paula Bachmann, Jane Louisa Debus, Marie-Celine Haker, Pegah Mashhadiakbar, Silvan Elias Langhorst, Julia Baldt, Barbara Streckenbach, Felicita Heidler, Uwe Klaus Zettl
Summary: This study compared three different screening tools for the detection and classification of potential drug-drug interactions (pDDIs) in multiple sclerosis (MS) patients, and identified factors associated with severe pDDIs. The results showed heterogeneity in the information on pDDIs between the examined databases, suggesting that multiple resources should be used in clinical practice to evaluate pDDIs. Regular medication reviews and information exchange between treating physicians can help prevent severe pDDIs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Elena Putscher, Michael Hecker, Brit Fitzner, Nina Boxberger, Margit Schwartz, Dirk Koczan, Peter Lorenz, Uwe Klaus Zettl
Summary: This study found that genetic variants from MS risk loci affect pre-mRNA splicing. These findings substantiate the role of alternative splicing events in the genetics of MS. Further research on how disease-causing genetic variants modify the interactions between splicing regulatory sequence elements and RNA-binding proteins can help deepen our understanding of the genetic susceptibility to MS.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Franziska Alfen, Elena Putscher, Michael Hecker, Uwe Klaus Zettl, Andreas Hermann, Jan Lukas
Summary: Fabry disease is a rare genetic disorder caused by mutations in the GLA gene. This study investigated the impact of these mutations on splicing behavior and found that abnormal splicing can lead to reduced enzyme activity and affect treatment options. Experimental analysis confirmed alternative splicing events for specific mutations, highlighting the importance of splicing phenotype analysis in studying exonic GLA gene mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Marie-Celine Haker, Niklas Frahm, Michael Hecker, Silvan Elias Langhorst, Pegah Mashhadiakbar, Jane Louisa Debus, Barbara Streckenbach, Julia Baldt, Felicita Heidler, Uwe Klaus Zettl
Summary: This study investigated the use of drugs with potential harm to the development of an unborn child in women with multiple sclerosis (MS). The majority of patients were found to be using drugs that are rated as having a potential risk of interfering with normal foetal development. More effective contraception and special pregnancy information programmes should be implemented to reduce potential risks to mother and child.
THERAPEUTIC ADVANCES IN DRUG SAFETY
(2023)
Article
Hematology
Robby Engelmann, Nadja Jaekel, Sabrina Jotschke, Beatrice Ludwig-Kraus, Frank Bernhard Kraus, Neha Kumari, Susann Schulze, Michael Hecker, Christina Zahn, Haifa Kathrin Al-Ali, Christian Junghanss, Sebastian Boettcher
Summary: In this study, the mechanisms of severe acute respiratory syndrome coronavirus 2 vaccination success in patients with hematological neoplasia were elucidated. The study found that patients with lymphoid malignancies had insufficient IgG response but healthy CD4+ T-cell function, while patients with myeloid neoplasia had fewer spike-specific CD4+ responses but normal seroconversion rate. It was also observed that vector-based vaccines were more effective in inducing CD4+ and CD8+ T-cell responses. The study provides valuable insights for tailored vaccination strategies in patients with hematological neoplasia.
Article
Immunology
Michael Hecker, Brit Fitzner, Nina Boxberger, Elena Putscher, Robby Engelmann, Wendy Bergmann, Michael Mueller, Isis Ludwig-Portugall, Margit Schwartz, Stefanie Meister, Ales Dudesek, Alexander Winkelmann, Dirk Koczan, Uwe Klaus Zettl
Summary: This study aimed to analyze the gene expression pattern of B cells before and during immune reconstitution therapy (IRT) in order to better understand the therapeutic effects and identify potential biomarkers of clinical response. The study found that B cells exhibited a distinct gene expression signature during IRT, and identified genes that could potentially indicate relapse risk.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Medicine, General & Internal
Julia Baldt, Niklas Frahm, Michael Hecker, Barbara Streckenbach, Silvan Elias Langhorst, Pegah Mashhadiakbar, Katja Burian, Janina Meissner, Felicita Heidler, Jorg Richter, Uwe Klaus Zettl
Summary: Polypharmacy is a significant issue in patients with multiple sclerosis, and it is associated with depression severity and comorbidities. A study on 374 MS patients found that patients with higher depression severity were more likely to be taking multiple medications, while anxiety was not correlated with polypharmacy. Furthermore, the frequency of comorbidities showed a positive correlation with anxiety and depression scores.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Jane Louisa Debus, Paula Bachmann, Niklas Frahm, Pegah Mashhadiakbar, Silvan Elias Langhorst, Barbara Streckenbach, Julia Baldt, Felicita Heidler, Michael Hecker, Uwe Klaus Zettl
Summary: This study aimed to determine the frequency and severity of potential drug-drug interactions (pDDIs) and potential drug-food interactions (pDFIs) in patients with multiple sclerosis (PwMS) who are taking multiple medications. The study found that patients with polypharmacy were particularly at risk of severe pDDIs.
THERAPEUTIC ADVANCES IN CHRONIC DISEASE
(2022)