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Copyright of Česká a Slovenská Neurologie a Neurochirurgie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The therapy of spinal muscular atrophy (SMA) with a link to 5q chromosome is nowadays a very hot area. A previously casually not treatable disease, it has been in the US since 2016, and in Europe since 2017. It is newly treatable, and nowadays there are three causal drugs. Two of them, nusinersen (Spinraza) and risdiplam (Ervysdi) increase the synthesis of the SMN protein by modulation of the RNA transcription of the SMN2 gene. These drugs have to be taken regularly, and are lifelong. The third drug, onasemnogene abeparvovec (Zolgensma) is able to substitute the missing SMN1 gene by a syntetic SMN1 gene delivered by viral vector AAV9. It is the first systemic gene therapy in medicine. Until now, this drug was taken only once. There are 4.5 years of data proving its sustaining effect. The first causal therapy was the drug Nusinersen. It has the huge advantage of 10 years’ experience with a high number of treated patients, more than 10,000. This drug does not go through the cerebro-spinal barrier, due to it having to be applied intrathecaly. Nusinersen is in CZ reimbursed for all types and ages of SMA patients. Recently, in August 2020, the drug risdiplam was registered in the US. Its advantage is per oral application; its disadvantage is the short experiences and limited acces in CZ. Risdiplam is not yet registered in the EU, due to this it is available only through the early access program for SMA patients type 1 and 2. The third causal therapy, and second registered drug in the EU, is onasemnogene abeparvovec. Due to the systemic delivery this therapy is limited only for children before the age of 3 years and weighing less than 13.5 kg. Besides, the already registered therapies there are many clinical trials with experimental drugs ongoing – many neuroprotective drugs and muscle strength-enhancing compounds. The actual therapy cannot help with all the symptoms of the disease, it can only mildly improve the motor function and primarily slow down the progression. Due to this, there is still a need for multidisciplinary symptomatic care that should be provided in Neuromuscular Centres. [ABSTRACT FROM AUTHOR]

Copyright of Česká a Slovenská Neurologie a Neurochirurgie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Česká a Slovenská Neurologie a Neurochirurgie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Česká a Slovenská Neurologie a Neurochirurgie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

There are potential renal risks in Duchenne (DMD) and Becker (BMD) muscular dystrophies in childhood, mainly a chronic exposure to myoglobin and, in some cases, genetic predispositions, if the dystrophin isoforms Dp140 and Dp 71 are lacking. We aimed to describe the renal parameters in boys with DMD and BMD, to identify early markers of renal damage. In a cross-sectional study, the levels of cystatin C, estimate of glomerular filtration according to Grubb (eGFRG), myoglobin, the presence of proteinuria, hemoglobin-/myoglobinuria (both from urinary chemical examination), creatinine, and protein excretion was noted together with blood pressure (BP), and height. We recorded historical urinary findings and myoglobin levels. We used descriptive statistics and tested hypotheses by linear regression, the Fisher exact test, and the unpaired T-test. In 51 boys with dystrophinopathy aged 4-15 years, the average eGFRG was 1,8 ± 0,4 ml/s/1,74m2. Surprisingly, eGFRG was lower than 1,5 ml/s/1,74m2 in 12/51 boys. A history of proteinuria and hemoglobin-/myoglobinuria was noted in 12/51 and 7/51 boys, respectively. Those with eGFR below 1,5 ml/s/1,74m2 had a higher incidence of proteinuria in their history (p=0,02). In those with a history of hematuria/myoglobinuria, the eGFRG was higher (2,06 vs. 1,78 ml/s/1,74m2, p = 0,04). The absence of Dp140 was associated with a higher incidence of hematuria/myoglobinuria (p = 0,01), but not proteinuria (p = 0,09). 18/51 boys BP above the 95th percentile, with no association with the studied markers. The renal function might be altered in boys with dystrophinopathy. Atypical finding in routine urine examination should trigger the evaluation of GFR from cystatin C, acid-base balance, and possibly the excretion of protein in 24-hour urine collection. The cause of the observed decreased eGFRG is not clear. Corticotherapy might increase the level of cystatin C and thus, in theory, lead to a falsly decreased eGFR. This study was supported by Charles University, project GA UK No: 586120, and Institutional Support of the Czech Ministry of Health, Project Nr. 6005. The authors are members of the European Reference Network for Rare Neuromuscular Diseases [ERN EURO-NMD]. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA), a rare neurodegenerative disorder with an estimated incidence of 1 in 6,000 to 10,000 live births, is the leading genetic cause of mortality in infants and children. Since the approval of new disease modifying treatments (DMTs; Spinraza in 2017, Zolgensma in 2020, and Evrysdi in 2021), studies have reported modified disease trajectories compared to the known SMA natural history. To describe the natural history of SMA and its progression during the use of DMTs in real-world settings, a retrospective cohort study was designed. Feasibility assessment identified six appropriate SMA registries to take part, comprising data from nine European countries (3 clinician-based registries: Belgium, Czech Republic & Slovakia, Sweden and 3 patient-based registries: Germany & Austria, Spain, UK & Ireland) between April 2008 and May 2023 federated in the TREAT-NMD network. Among 2,188 SMA patients with genetically confirmed 5q SMA, more patients had SMA type 2 (41.8%) than type 3 (35.6%) and type 1 (19.7%); 1,321 (60.3% overall) were treated with Spinraza (75,9%), Evrysdi (30.5%) or Zolgensma (7.6%), and 847 (38.7%) never received treatment. Functional status and motor milestones were rarely reported in never treated patients. Among treated patients, best functional status for SMA types 1, 2, and 3 was "sitter" for 36.6%, 60.9%, and 5.3%, and "walker" for 12.0%, 24.6%, and 87.8% respectively. Best motor milestone for types 1 and 2 was "sit without support" for 27.2% and 38.0%, and "roll onto side" for 18.5% and 2.0% respectively. For type 3, 63.4% reported "climb stairs" and 19.3% reported "walk 10 meters without assistance". Functional status and motor milestones were well captured after treatment but rarely reported before, limiting evaluation of treatment related changes. Areas of improvement for registry data quality have been identified to reduce data missingness, increase standardization, and enhance their utility to inform regulatory decision making. Disclaimer: "This study was funded by the European Medicines Agency and registered in EU PAS (EUPAS50476). The views expressed in this abstract are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the regulatory agency/agencies or organizations with which the authors are employed/affiliated." [ABSTRACT FROM AUTHOR]

Risdiplam (EVRYSDI®) is a disease-modifying therapy approved for the treatment of spinal muscular atrophy (SMA). The efficacy of risdiplam has been demonstrated in clinical trials that included adult patients, but the real-world effectiveness of risdiplam in adults has not yet been extensively investigated. Natural history studies have shown a slow, progressive decline in motor function in adult patients with SMA. It remains unclear how treatment with risdiplam may influence this trajectory in a real-world clinical setting. As such, this study aims to describe adult patients with SMA treated with risdiplam in terms of their demographic and clinical characteristics, treatment patterns and motor function outcomes, and explore, if possible, the comparison of these outcomes with untreated patients. This non-interventional, retrospective cohort study will use data from six registries (clinician and patient reported) from within the TREAT-NMD network (Australia, Belgium, Canada, Czech Republic & Slovakia, Germany & Austria, and the UK & Ireland) to identify adult patients with SMA treated with risdiplam and where feasible, compare with an untreated patient population. Appropriate adjustment methods will be explored to account for potential confounders where possible, and appropriate statistical models will be used to perform comparisons with untreated patients. As of the submission of this abstract, the analysis is ongoing. Available data will be presented with descriptive statistics. In sum, this study will add to the growing real-world evidence for risdiplam in adults. This study will help to contextualise the effect of risdiplam in this patient population and that of untreated patients. [ABSTRACT FROM AUTHOR]