Neuromuscular Disorders最新文献

{"title":"145P Efficacy of SMA NBS: 4-year comparative study with control group","authors":"T. Dangouloff ,&nbsp;L. De Waele ,&nbsp;D. Beysen ,&nbsp;N. Smeets ,&nbsp;A. Vanlander ,&nbsp;N. Benmhammed ,&nbsp;C. Tychon ,&nbsp;A. Daron ,&nbsp;N. Deconinck ,&nbsp;P. Dontaine ,&nbsp;L. Servais","doi":"10.1016/j.nmd.2024.07.052","DOIUrl":"10.1016/j.nmd.2024.07.052","url":null,"abstract":"<div><div>Several newborn screening (NBS) programs for Spinal Muscular Atrophy (SMA) have demonstrated feasibility-reliability and short-term efficacy of PCR-based universal SMA NBS, but longer-term data are needed to precise the benefit of this intervention. In addition, the comparison with external control groups can reinforce the level of evidence and support robust health economic assessment. The aim of this study is to compare the medical, quality of life and economic data for SMA patients diagnosed by NBS and those identified by symptoms, in the same country, during the same time period. We collected data on all SMA patients born in Flanders and the Wallonia-Brussels Federation (FWB) between January 1, 2019 (the date on which the entire FWB began screening for SMA) and 30 November 2022 (the date on which Flanders began screening). We compared the median age of diagnosis and initiation of treatment, the treatment, scores on motor development scales, and the age of acquisition of sitting and walking. We also collected quality of life data for parents, utility data for children, and costs associated with the disease. A total of 30 patients were included in the analysis: 16 patients in FWB (7 with 2 SMN2 copies, 4 with 3 copies and 5 with 4 copies) and 13 in Flanders. One patient with a point mutation was not identified by NBS in FWB. Patients in FWB were initially treated by nusinersen (n = 5) risdiplam (n = 3) and onasemnogene abeparvovec (n = 7) at 36 days of life on average (29, 37, and 44 days respectively for patients with 2, 3 and 4 SMN2 copies of SMN2). Two patients shifted from nusinersen to risdiplam, one from nusinersen to onasemnogene abeparvovec and one from risdiplam to onasemnogene abeparvovec. One patient with 4 SMN2 copies was still untreated at 26 months. Median follow up was 32 months (9-54 months). All patients over 18 months with 3 and 4 SMN2 copies acquired ambulation (median age: 17 months, 13-24 months). Of the 7 patients with 2 SMN2 copies, 2 are not yet 18 months old, 4 are walking, and one aged 24 months is not yet walking. One child with 2 SMN2 copies have non-invasive nocturnal ventilation. None of the children needed nutritional support at the time of the last follow-up. Data in Flanders, where NBS was not implemented in the studied time, are currently collected, and will be presented during the congress. Our data shows that middle term outcome of patients identified by NBS is very good so far. Estimation of health care cost saving will be presented.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.43"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"136P Medical treatment of children with spinal muscular atrophy - An investigation of parents' experiences of hopes, worries and need for rehabilitation for their child","authors":"C. Handberg ,&nbsp;U. Werlauff ,&nbsp;P. Drivsholm ,&nbsp;S. Lorenzen ,&nbsp;A. Mahoney","doi":"10.1016/j.nmd.2024.07.043","DOIUrl":"10.1016/j.nmd.2024.07.043","url":null,"abstract":"<div><div>In Denmark, newborn screening was introduced at the beginning of 2023, and per July 2023 the Medical Council recommended medical treatment of SMA for children, young people, and adults up to and including 25 years of age who meet the inclusion criteria in the treatment guidelines. The medical advances give both children, parents and health professionals hope for a new life with SMA. The children receive treatment at the pediatric departments at university hospitals in Denmark and most of them are referred to the Danish National Rehabilitation Centre for Neuromuscular Diseases (RCFM) where they and their families receive guidance and advice from rehabilitation specialists. There is currently scant knowledge about how parents of a child with SMA type 1, 2 or 3 experience their child's illness, their contact with health professionals, and their needs for information and advice on the medical treatments and its effect. The aim of the project is to gain knowledge about how Danish parents whose children with SMA have been offered medical treatment handle hopes and worries in relation to disease progression. And to investigate the families’ needs for information, advice, and rehabilitation initiatives. The study was designed as a qualitative interview study guided by the interpretive description methodology and Joyce Travelbee's theory of interpersonal aspects such as suffering, meaning, hope and communication. The method was semi-structured couple interviews with parents of children with SMA type 1, 2 and 3 aged 14 and younger. In all, 41 couples with children registered at RCFM were invited to participate. Nineteen couples (38 parents) accepted the invitation. The analysis is ongoing, and the results will be presented on the conference poster.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.34"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"143P Swallowing physiology and function in untreated patients with Spinal Muscular Atrophy type 1: establishing natural history reference values","authors":"K. McGrattan ,&nbsp;R. Graham ,&nbsp;A. Miles ,&nbsp;J. Allen ,&nbsp;A. Hofelich Mohr ,&nbsp;V. Rao ,&nbsp;L. Alfano ,&nbsp;L. Smith ,&nbsp;J. Brandesma ,&nbsp;C. Leon Astudillo ,&nbsp;D. Levy ,&nbsp;W. Tang ,&nbsp;A. Brown ,&nbsp;A. Spoden ,&nbsp;G. Schenck ,&nbsp;B. Darras","doi":"10.1016/j.nmd.2024.07.050","DOIUrl":"10.1016/j.nmd.2024.07.050","url":null,"abstract":"<div><div>Dysphagia has been a leading source of morbidity in patients with spinal muscular atrophy type 1 (SMA 1). The paucity of investigations has impeded the ability to judge the effect of disease modifying therapies (DMT). We report a natural history dataset characterizing swallowing biomechanics and function in untreated children with SMA 1. Infants with SMA 1 who had not received DMT and underwent a videofluoroscopic swallow study (VFSS) were retrospectively identified from 13 international children's hospitals. Charts were reviewed for oral intake and secretion management. VFSS’ were prospectively evaluated for biomechanics. Differences in swallowing between patients referred for VFSS due to swallowing concerns vs. those referred as part of a routine high-risk referral were tested using paired t-tests. Of the 77 children included, 30% of required suctioning, and 39% received alternative nutrition. Profound deficits were observed in sucking, with the inability to extract a bolus in 25% of children. Impairments in bolus clearance were common, with severe reductions in tongue base retraction (49%), absent pharyngeal stripping wave (23%), and minimal to no upper esophageal segment opening (50%) resulting in a majority-no clearance of the bolus from the pharynx in 40% of children. Pharyngeal constriction ratio (0.41 ± 0.28) and upper esophageal segment opening (0.12 ± 0.09) were consistent with these results. More than trace aspiration (56%) on &gt;1 occurrence was seen in 52% of children. Deficits were significant worse in patients referred due to symptoms than asymptomatic (p &lt; 0.05). Without pharmaceuticals patients with type 1 SMA exhibit profound deficits in swallowing. Although the presence of clinical signs of swallowing impairment may identify those children with the most profound deficits, they are not reliable for identifying a magnitude of other clinically significant impairments.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.41"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"276P Exploring muscle endurance in a neuromuscular population: insights from the assisted 6-minute cycling test combined with cardiopulmonary exercise testing and near-infrared spectroscopy","authors":"W. Tang,&nbsp;C. de Monts,&nbsp;S. Montalvo,&nbsp;S. Dunaway Young,&nbsp;S. Salvatore,&nbsp;S. Khonde,&nbsp;S. Smith,&nbsp;N. Hageman,&nbsp;Y. Blumberg,&nbsp;P. Ataide,&nbsp;N. Ni Ghiollagain,&nbsp;D. Parker,&nbsp;M. Wheeler,&nbsp;J. Day,&nbsp;M. Wheeler,&nbsp;T. Duong","doi":"10.1016/j.nmd.2024.07.094","DOIUrl":"10.1016/j.nmd.2024.07.094","url":null,"abstract":"<div><div>Assessing muscle endurance in weak individuals with neuromuscular disease (NMD) is challenging given physiological limitations. By integrating Cardiopulmonary Exercise Testing (CPET) and Near-Infrared Spectroscopy (NIRS) with the Assisted 6-Minute Cycling Test (A6MCT), we can explore the interplay of muscle oxygenation dynamics and metabolic demands during exercise. We collected data from 56 individuals with SMA (n=41,73.2%) and DMD (n=15,22.8%). Patients were 15-74 years (avg=30.5±13.2) and ranged in function (non-sitters=35.7%; sitters=44.6%; walkers=19.6%). Fatigability (%fatigue) during a maximal effort A6MCT was assessed by calculating the percent change in revolutions between first and last minute, while total work was determined by total revolutions. Peak aerobic capacity (peak VO2) was measured using a metabolic cart (K5 COSMED USA), while changes in deoxygenated hemoglobin were measured by NIRS sensors placed on biceps and triceps (ΔHHbb;ΔHHbt). Perceived exertion at the end of the 6-minutes (OMNI score) was collected, as were peak heartrate (peak HR) during exercise and Forced Vital Capacity (FVC%) at rest. Baseline analysis revealed that total revolutions positively correlated with FVC% (r=0.663; p=0.003), peak VO2 (r=0.753; p&lt;.001), and peak HR (r=0.500; p=0.008). Meanwhile, OMNI score is correlated with peak VO2 (r=0.444; p=0.034) and peak HR (r=0.700; p&lt;0.001). When assessing NIRS, mean HHb in biceps during exercise is positively correlated with peak VO2 (r=0.537; p=0.008), while mean HHb recovery in biceps is inversely correlated with %Fatigue (r=-0.475; p=0.011). The observed correlations between ventilation and muscle oxygen uptake in individuals with NMD reveal a distinctive mechanistic relationship that potentially influences endurance and fatigability. Further exploration combining these exercise testing modalities may yield valuable insights for assessing the metabolic demands of muscle performance during aerobic exercise. In addition, these findings may provide future direction for identifying underlying causes in the mismatch between ventilatory and peripheral oxygen uptake that leads to the increased fatigability in the NMD population.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.85"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"232VP Patient knowledge of the risks of glucocorticoid management in a specialist adult muscle clinic","authors":"L. Kent,&nbsp;F. Begeti,&nbsp;H. Turner,&nbsp;S. Brady","doi":"10.1016/j.nmd.2024.07.083","DOIUrl":"10.1016/j.nmd.2024.07.083","url":null,"abstract":"<div><div>The prescribing of long-term glucocorticoids has recently been highlighted as a safety concern within the NHS due to the risk of adrenal suppression and subsequent adrenal crisis during intercurrent illness. In a recent four-year period, the National Reporting and Learning System (NRLS) identified 2 deaths, 6 incidents of severe harm, and 70 other incidents of harm related to this medication. We conducted this study to ascertain the level of risk in our clinic and implement strategies to improve patient safety. To evaluate and improve glucocorticoid management in patients under the Adult Oxford Muscle Service, we conducted structured telephone interviews with patients on this treatment [Duchenne muscular dystrophy (DMD) and idiopathic inflammatory myopathy (IIM)] and their families. Twenty patients were included, 11 with a diagnosis of DMD (all male) and 9 with a diagnosis of IIM (5 male). The age range was 18 - 81 years and current glucocorticoid dose was 7 - 50 mg prednisolone daily. Our results revealed that patients frequently were not confident about what to do if they were unwell or missed a dose of glucocorticoid. The proportion that did not know what to do when unwell was 70%, when vomiting was 60%, and with symptomatic SARS-CoV-2 (Covid-19) infection was 75%. Ten patients (50%) did not carry a steroid card. Knowledge across this group varied considerably. Our study highlighted the fact that this cohort of patients (and their families) are often unaware how to manage their medication safely, putting them at risk of complications of adrenal suppression. These findings helped us to implement strategies to reduce this risk including frequently reiterated written and oral guidance on glucocorticoid therapy and its potential complications. We anticipate that this significantly reduces the risk of patient harm. Given the almost ubiquitous use of glucocorticoids in many areas of medicine, we feel it is useful for others to consider similar studies in their practice.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.74"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"06O NLRP3 inflammasome activation and altered mitophagy are key pathways in inclusion body myositis","authors":"E. Naddaf ,&nbsp;T. Nguyen ,&nbsp;J. Watzlawik ,&nbsp;H. Gao ,&nbsp;X. Hou ,&nbsp;F. Fiesel ,&nbsp;J. Mandrekar ,&nbsp;E. Kokesh ,&nbsp;W. Harmsen ,&nbsp;I. Lanza ,&nbsp;W. Springer ,&nbsp;E. Trushina","doi":"10.1016/j.nmd.2024.07.019","DOIUrl":"10.1016/j.nmd.2024.07.019","url":null,"abstract":"<div><div>Inclusion body myositis (IBM) is the most prevalent muscle disease in adults for which no current treatment exists. The pathogenesis of IBM remains poorly defined. Inflammation and mitochondrial dysfunction are the most common histopathological findings. In this study, we aimed to explore the interplay between inflammation and mitochondrial dysfunction in IBM patients. We included 38 IBM patients and 22 age- and sex-matched controls without myopathy. Bulk RNA sequencing, Meso Scale Discovery ELISA, western blotting, histochemistry and immunohistochemistry were performed on frozen muscle samples from the study participants. We demonstrated activation of the NLRP3 inflammasome in IBM muscle samples, with the NLRP3 inflammasome pathway being the most upregulated pathway. On muscle histopathology, there was increased NRLP3 immunoreactivity in both inflammatory cells and muscle fibers. Mitophagy is critical for removing damaged mitochondria and preventing the formation of a vicious cycle of mitochondrial dysfunction—NLRP3 activation. In the IBM muscle samples, we showed altered mitophagy with elevated levels of p-S65-Ubiquitin, a mitophagy marker. Furthermore, p-S65-Ubiquitin aggregates accumulated in muscle fibers that were mostly type 2 and devoid of cytochrome-c-oxidase reactivity. Type 2 muscle fibers are known to be more prone to mitochondrial dysfunction. NLRP3 RNA levels correlated with p-S65-Ubiquitin levels. NLRP3 inflammasome is activated in IBM, along with altered mitophagy, potentially forming a self-sustaining vicious cycle. These findings could have potential therapeutic significance.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.10"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"216P A questionnaire-based investigation into levels physical disability and of physical activity in adults with neuromuscular disease in a UK neuromuscular centre","authors":"T. Willis ,&nbsp;K. Strachan ,&nbsp;N. Emery","doi":"10.1016/j.nmd.2024.07.067","DOIUrl":"10.1016/j.nmd.2024.07.067","url":null,"abstract":"<div><div>Neuromuscular diseases (NMD) are either genetic or acquired, and to date, most have no specific pharmaceutical intervention effective in arresting or improving disease progression. They are, therefore, all progressive in nature with a gradual or rapid loss of functional abilities; loss of ambulation, upper or lower limb weakness or both, loss of independence and associated co-morbidities; respiratory, cardiac, diabetes, and obesity. Neuromuscular diseases are complex and require careful management. One intervention that is available to most NMD patients is physical activity (PA). Physical activity has been shown to have benefits and be safe for those with NMD. Therefore, NMD patients should be encouraged to engage in physical activity. To assess adult patients with NMD and participation in physical activity, the 'Rapid Assessment of Physical Activity' (RAPA) was used. This is a patient questionnaire that uses a 'yes/no' format with 7 fields, with 1 being no physical activity to 7 being vigorous activity for 20 minutes, 3 or more times, per week. Stretching and resistance training are also assessed. To determine the level of physical impairment the 'Summary of Functional Tests' (SOFT) was used. This simple assessment tool provides a quantitative description of a person's physical function. We present the results (n=66) of a prospective review of adult patients seen in a NM clinic between May and December 2023 and delivered and assessed by 2 NM specialist physiotherapists. Taken together the RAPA plus the SOFT should provide an overview of the level of physical activity engagement and physical impairment. Findings can used to determine if NMD patients engage in physical activity and if this is at the recommended amount, as per the American College of Sports Medicine guidelines.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.58"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"224P Psychosocial discussions in neuromuscular clinics from a professional lens: evidence from a service evaluation regarding barriers to discussions","authors":"C. Geagan,&nbsp;A. Sandhu,&nbsp;J. Mason,&nbsp;M. McCallum,&nbsp;R. Muni-Lofra,&nbsp;D. Moat,&nbsp;K. Wong,&nbsp;E. Robinson,&nbsp;E. Grover,&nbsp;J. Michel-Sodhi,&nbsp;C. Bolaño Diaz,&nbsp;M. Schiava,&nbsp;D. Salman,&nbsp;M. James,&nbsp;G. Tasca,&nbsp;J. Diaz Manera,&nbsp;M. Guglieri,&nbsp;V. Straub,&nbsp;M. Elseed,&nbsp;C. Marini Bettolo","doi":"10.1016/j.nmd.2024.07.075","DOIUrl":"10.1016/j.nmd.2024.07.075","url":null,"abstract":"<div><div>Neuromuscular disorders have a high symptom burden and are frequently associated with many adverse psychosocial outcomes, particularly reduced quality of life and well-being. For some conditions, such as Duchenne muscular dystrophy, quality of life can be further affected by additional neurodevelopmental and cognitive needs. For individuals with neuromuscular condition, effective clinical care involves addressing the physical aspects of a condition, and the emotional and social dimensions that accompany it. Professionals working in neuromuscular teams frequently provide emotional support for individuals and their families with Neuromuscular conditions. However, it can be challenging to have these discussions in routine clinics. A retrospective audit of paperwork from routine muscle reviews throughout 2022 and 2023 was conducted to identify levels of psychosocial need in routine muscle reviews at a specialist Neuromuscular centre in Northern England, The John Walton Muscular Dystrophy Research Centre. Online surveys were distributed to clinicians within the team to discuss current challenges and facilitators of mental health discussions in clinic. This study aimed to (1) examine the frequency of mental health or cognitive discussions in clinic (2) understand the nature of psychosocial concerns raised in clinic, (3) identify potential barriers to these discussions as identified by multidisciplinary professionals within the team. Both paediatric and adult clinics were included, and no exclusion criteria regarding neuromuscular condition applied. Audit and evaluation are currently ongoing. The current audit and service evaluation will contribute to service development looking at improving psychosocial support in Neuromuscular care within the UK. A re-audit and evaluation next year will assess whether recommendations better facilitate these conversations within neuromuscular clinics.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.66"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"226P Phase 3, randomized, global study assessing efficacy and safety of del-desiran for the treatment of myotonic dystrophy type 1: HARBOR trial design","authors":"M. Fowler ,&nbsp;N. Johnson ,&nbsp;C. Thornton ,&nbsp;J. Day ,&nbsp;V. Sansone ,&nbsp;B. McEvoy ,&nbsp;L. Tai ,&nbsp;B. Knisely ,&nbsp;T. Brandt ,&nbsp;K. Gallagher ,&nbsp;S. Hughes ,&nbsp;E. Ackermann","doi":"10.1016/j.nmd.2024.07.077","DOIUrl":"10.1016/j.nmd.2024.07.077","url":null,"abstract":"<div><div>Myotonic dystrophy type 1 (DM1) is a rare, dominantly inherited, progressive neuromuscular disease caused by a toxic gain-of-function mutation in the DM1 protein kinase (DMPK) gene. DM1 is primarily characterized by myotonia along with progressive muscular weakness and wasting, leading to deficits in hand function, immobility, respiratory insufficiency, dysarthria, and dysphagia. Hand function impairment is caused by both myotonia and hand weakness leading to negative impact on quality of life. Delpacibart etedesiran (del-desiran, formerly AOC 1001) is an antibody-oligonucleotide conjugate (AOC™) comprised of a DMPK siRNA conjugated to a humanized antibody targeting transferrin receptor 1 (TfR1) for delivery of siRNA to muscle cells to mediate DMPK mRNA degradation addressing the underlying cause of DM1. Long-term safety and tolerability data from the Phase 1/2 MARINA® and MARINA-OLE™ clinical trials demonstrated that del-desiran is well tolerated in patients with DM1 and demonstrated efficacy compared to placebo and natural history for multiple functional endpoints. This phase 3, randomized, double-blind, placebo-controlled, 54-week study will be conducted across ∼40 global sites. This study will enroll participants aged 16+ years with a clinical and genetic diagnosis of DM1 (DMPK CTG repeat ≥100). Participants will be randomized 1:1 to receive either 4 mg/kg del-desiran or placebo administered intravenously every 8 weeks. The first dose of del-desiran will be 2 mg/kg. Primary analysis will take place at Week 30, with the duration of the placebo-controlled study being 54 weeks. Eligible participants will have the option to enroll in an open-label extension trial. The primary objective is to evaluate the efficacy of del-desiran on hand opening time to observe changes in myotonia and hand function. Key secondary objectives are to evaluate the efficacy of del-desiran on muscle strength and activities of daily living.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.68"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"122P A retrospective review of changes in upper limb function following spinal surgery in spinal muscular atrophy","authors":"O. Martineau ,&nbsp;E. Milev ,&nbsp;M. Main ,&nbsp;M. Scoto ,&nbsp;F. Muntoni ,&nbsp;G. Baranello","doi":"10.1016/j.nmd.2024.07.029","DOIUrl":"10.1016/j.nmd.2024.07.029","url":null,"abstract":"<div><div>In recent years, disease-modifying treatments (DMT) for Spinal Muscular Atrophy (SMA) have become readily available on the National Health Service in the UK. Although phenotypes are changing, progressive scoliosis remains common and can affect individuals' quality of life causing a negative impact on mobility, increased pain and worsened respiratory function. Corrective spinal surgery aims to reduce the curvature of the spine with the purpose to improve sitting posture and lung function. Limited data is available on the effects of scoliosis surgery on upper limb function in SMA patients. The revised upper limb module (RULM) is used to monitor changes in the arm function in the SMA cohort assessing both proximal and distal activities. The aim of this study is to review changes in upper limb function of SMA children following spinal surgery identifying possible contributing factors. A single-centre retrospective review has been completed of the current SMA cohort at Great Ormond Street Hospital (GOSH) that underwent corrective spinal surgery (posterior spinal fusion or growth rod insertion). Forty-two patients were identified; 20 were excluded due to insufficient data. Of the remaining 22 patients, 14 were female and 8 male. Nine were classified as type 3, 12 as type 2 and 1 as type 1;12/22 had started on DMT prior to surgery. Scores from 2 RULM assessments taken prior to surgery at least 6 months apart were compared with RULM results post-surgery at two 6-month intervals. Other factors were recorded including age, Cobb angle and time on DMT prior to surgery. Patients receiving DMT post-surgery were used as a control group. At the initial follow-up, 64% showed a decline in RULM score with an average change in score of-2.18. At the second follow-up, 78% had improved or maintained their score with an average score change of 0.09. Comparing the treated and untreated group, there was no significant difference in scores at the initial follow-up, while at the second follow up a significant difference was observed (p=0.018) with an average change of +1 in the DMT group compared to -1 in the untreated group. Our study shows that children with SMA treated with a DMT prior to surgery declined initially however 87% regained or maintained some upper limb function at their second follow-up. We aim to further analyse the data and present the full scope of this study including a larger group across the UK.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.20"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}