Friedreichova ataxie (FA) představuje nejčastější autozomálně recesivní dědičnou ataxii. Její patogenetickou podstatou je mitochondriální dysfunkce v důsledku snížené exprese genu FXN pro protein frataxin. První příznaky FA se objevují charakteristicky ve druhé dekádě života ve věku mezi 10 a 15 lety. I přes kontinuální intenzivní výzkum zůstává zatím FA nevyléčitelnou nemocí. Omaveloxolon patří do specifické třídy léčiv nazývaných modulátory Nrf2 (nukleární transkripční faktor) a je prvním lékem schváleným pro pacienty s FA, jenž zasahuje přímo do patofyziologie nemoci. Omaveloxolon přináší pacientům naději na zpomalení progrese onemocnění a významné zlepšení kvality života.

Friedreich ataxia (FA) is the most common form of hereditary ataxia with an autosomal recessive inheritance pattern. Mitochondrial dysfunction is a central contributor to pathology in FA, resulting from decreased levels of functional frataxin protein, coded by the FXN gene. Initial symptoms of FA usually appear around the beginning of the second decade of life between 10 and 15 years. There is currently no cure for FA, despite ongoing intensive research efforts. Omaveloxolone belongs to a specific class of medications known as Nrf2 (nuclear factor erythroid 2-related factor 2) modulators and it is the first drug approved for FA, directly applicable to the disease pathophysiology. Omaveloxolone offers a big hope to patients for slowing the progression of the disease and significant improvement in quality of life.

• Klíčová slova
• omaveloxolon,
• MeSH
• diagnostické techniky molekulární MeSH
• frataxin genetika   MeSH
• Friedreichova ataxie * diagnóza   genetika   terapie   MeSH
• lidé MeSH
• triterpeny farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: Cladribine, a selective immune reconstitution therapy, is approved for the treatment of adult patients with highly active multiple sclerosis (MS). OBJECTIVES: Provide experience with cladribine therapy in a real-world setting. METHODS: This is a registry-based retrospective observational cohort study. First, using data from the Czech nationwide registry ReMuS, we analysed patients who initiated cladribine from September 1, 2018 to December 31, 2021. Second, we analysed a subgroup of patients who initiated cladribine between September 1, 2018 to June 30, 2020, thus possessing a follow-up period of at least 2 years. We evaluated demographic and MS characteristics including disease-modifying therapies (DMTs) before and after cladribine administration, relapses, Expanded Disability Status Scale (EDSS), and adherence. RESULTS: In total, 617 patients (335 with follow-up of at least 2 years) started cladribine therapy in the study period (mean age 37.0, mean disease duration 8.4 years, 74.1% females). In most cases, cladribine was administered as a second-line drug, a total of 80.7% had been escalated from a platform DMT. During 2 years before cladribine initiation, the average annualised relapse rate (ARR) was .67. Following cladribine initiation, the ARR decreased to .28 in the first year and .22 in the second year. Overall, across the entire two-year treatment period, 69.0% of patients were relapse-free and the average ARR was .25. As for EDSS development, the median baseline EDSS was 2.5 and remained stable even after 24 months. The adherence to treatment ranged of around 90%. CONCLUSION: This nationwide study confirms the efficacy of cladribine in real-world settings, especially in patients who are not treatment-naïve. In addition, the study shows an exceptionally high adherence rate, a finding that underscores the invaluable role of cladribine, but also the value of registry-based studies in capturing real-world clinical practice.

• Publikační typ
• časopisecké články MeSH

Sekundárně progresivní roztroušená skleróza (SP-RS) představuje druhou nejčastější formu roztroušené sklerózy. Je pro ni charakteristické plynulé zhoršování neurologických obtíží s přítomností pouze ojedinělých relapsů nebo jejich úplnou absencí. Účinný lék pro pacienty se SP-RS na evropském trhu dlouho chyběl. Siponimod, selektivní modulátor sfingosin-1-fosfátových receptorů, je prvním přípravkem, u kterého bylo prokázáno zpomalení klinicky potvrzené progrese. Kazuistika popisuje téměř 19leté období ženy léčené pro roztroušenou sklerózu.

Secondary progressive multiple sclerosis (SP-MS) is the second most common form of multiple sclerosis. It is characterized by insidious worsening of neurologic function over time, with the reduction in the frequency of relapses or complete absence of relapse activity. An effective treatment for patients with SP-MS was lacking on the European market for a long time. Siponimod, a selective modulator of sfingosin-1-phosphate receptors, is the first drug to treat SP-MS, that showed a significant decrease in disability progression. A case study describes almost 19-year period of woman treated with multiple sclerosis.

The aim of this study was to conduct QuantiFERON Monitor (QFM) testing in patients with multiple sclerosis (MS), which is used to monitor the state of the immune system through the non-specific stimulation of leukocytes followed by determining the level of interferon-gamma (IFN-γ) released from activated cells. Additionally, we tested the level of selected cytokines (IFN-α, IFN-γ, IL-1α, IL-1β, IL-1ra, IL-2, IL-3, IL-4, IL-6, IL-7, IL-10, IL-15, IL-33, VEGF) from stimulated blood samples to further understand the immune response. This study builds upon a previously published study, utilizing activated serum samples that were initially used for IFN-γ determination. However, our current focus shifts from IFN-γ to exploring other cytokines that could provide further insights into the immune response. A screening was conducted using Luminex technology, which yielded promising results. These results were then further elaborated upon using ELISA to provide a more detailed understanding of the cytokine profiles involved. This study, conducted from August 2019 to June 2023, included 280 participants: 98 RRMS patients treated with fingolimod (fMS), 96 untreated patients with progressive MS (pMS), and 86 healthy controls (HC). Our results include Violin plots showing elevated IL-1α in pMS and fMS. Statistical analysis indicated significant differences in the interleukin levels between groups, with IL-1ra and age as key predictors in differentiating HC from pMS and IL-1ra, IL-1α, age, and EDSS in distinguishing pMS from fMS. These findings suggest cytokines' potential as biomarkers in MS progression and treatment response.

• MeSH
• antagonista receptoru pro interleukin 1 MeSH
• cytokiny MeSH
• imunitní systém MeSH
• interferon gama MeSH
• lidé MeSH
• roztroušená skleróza * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Ozanimod je lék hrazený k léčbě relaps-remitentní roztroušené sklerózy (RRRS) a ulcerózní kolitidy, v současné době je vyhodnocována studie jeho vlivu na Crohnovu chorobu. Stran léčby RRRS byla v několika studiích prokázána jeho účinnost oproti již zavedené léčbě i jeho příznivý bezpečnostní profil. Tento článek představuje kazuistiku pacienta s RRRS a UC, který byl léčen ozanimodem. Muž, u něhož byla ve 22 letech diagnostikována RRRS, prodělal během 17 let tři relapsy míšní symptomatiky a byl postupně léčen několika imunomodulačními léky, v roce 2023 byla zahájena léčba ozanimodem. Tato kazuistika naznačuje potenciál ozanimodu v léčbě pacientů s RRRS, kteří trpí i dalším autoimunitním onemocněním, jako je ulcerózní kolitida.

Ozanimod is a drug approved for the treatment of reiapsing-remitting multiple sclerosis (RRMS) and ulcerative colitis, and study results evaluating its effect on Crohn’s disease are currently being evaluated. In terms of RRMS treatment, several studies have demonstrated its efficacy compared to established therapies and its favorable safety profile. This article presents a case study of a patient with RRRS and ulcerative colitis who was treated with ozanimod. The patient, diagnosed with RRMS at the age of 22, experienced four relapses of spinal symptoms over 17 years and underwent various immunomodulatory treatments before starting ozanimod in 2023. This case suggests the potential of ozanimod in treating RRMS patients who also suffer from other autoimmune diseases, such as and ulcerative colitis.

Roztroušená skleróza (RS) je chronické zánětlivé autoimunitní onemocnění postihující centrální nervový systém. Současná léčba, zejména pokud je zahájena v časné fázi onemocnění, dokáže zpomalit progresi choroby a tím i oddálit invaliditu pacientů. Jedním z cílů léčby u pacientů s RS je dosažení stavu bez klinických i subklinických známek aktivity onemocnění, tedy stavu označovaného jako NEDA (no evidence of disease activity). Práce se zabývá parametrem NEDA‐3 z pohledu současné léčby RS.

Multiple sclerosis is a chronic inflammatory autoimmune disease which affects central nervous system. Initiation of the treatment early in the course of multiple sclerosis may postpone the disease progression and development of disability. One of the goals of MS treatment is a state without clinical and subclinical markers of disease activity, known as NEDA (No Evidence of Disease Activity). This work focuses on the concept of NEDA‐3 with respect to the current treatment of MS.

• Klíčová slova
• NEDA-3,
• MeSH
• lidé MeSH
• progrese nemoci MeSH
• roztroušená skleróza * diagnóza   terapie   MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé MeSH