Neuromuscular Disorders最新文献

{"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":"221P Initial data from the achieve trial of DYNE-101 in adults with myotonic dystrophy type 1 (DM1)","authors":"D. Wolf ,&nbsp;J. Lilleker ,&nbsp;G. Bassez ,&nbsp;J. Diaz-Manera ,&nbsp;J. Kools ,&nbsp;M. Pane ,&nbsp;R. Roxburgh ,&nbsp;B. Schoser ,&nbsp;C. Turner ,&nbsp;C. Mix ,&nbsp;S. Ray ,&nbsp;B. Han ,&nbsp;W. Farwell ,&nbsp;V. Sansone","doi":"10.1016/j.nmd.2024.07.072","DOIUrl":"10.1016/j.nmd.2024.07.072","url":null,"abstract":"<div><div>DM1 is a spliceopathy caused by expansion of CUG repeats in the DMPK RNA that leads to multisystem clinical manifestations. DYNE-101, an investigational therapeutic for treatment of DM1, consists of a TfR1-binding Fab conjugated to an ASO designed against mutant nuclear DMPK RNA to correct splicing. The safety and efficacy of DYNE-101 in adults (18-49 years old) are being investigated in the Phase1/2 ACHIEVE trial (NCT05481879). For this analysis, 16 participants had efficacy data through 6 months (6M) of follow-up in the 1.8 mg/kg (approximate ASO) dose cohort and 16 participants had biopsy data through 3M of follow-up in the 3.4 mg/kg dose cohort of the MAD portion of ACHIEVE. Participants were randomized to receive DYNE-101 (n=6) or placebo (n=4) Q4W, or two doses of DYNE-101 followed by placebo for the remainder of the MAD period (n=6). Safety and tolerability are based on 45 participants enrolled in ACHIEVE as of the data cut-off date. At 3M, 1.8 and 3.4 mg/kg DYNE-101 showed mean 10.0 ng/g and 21.5 ng/g ASO concentration, mean 25% and 40% DMPK knockdown, and mean 13% and 19% splicing correction from baseline, respectively. At 6M, 1.8 mg/kg DYNE-101 showed mean 16% DMPK knockdown, +7% CASI change from baseline, 3.8-second improvement in myotonia, and improvement in MDHI, a patient-reported outcome. 3/5 evaluable participants had splicing correction at 3M, persisting through 6M. In the 3.4 mg/kg cohort, 5/5 evaluable participants had splicing correction at 3M. DYNE-101 had a favorable safety profile as of the data cut-off date, with mostly mild or moderate TEAEs and no clinically meaningful changes in kidney and liver parameters or treatment-emergent anemia. The initial data with DYNE-101 demonstrated dose-dependent ASO delivery, DMPK knockdown, and splicing correction with durable effect. Improvement in myotonia was also observed at the lowest dose tested. The data support the continued development of DYNE-101 for the treatment of DM1.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.63"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423651","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":"223P Mental health support for children and young people with Duchenne muscular dystrophy – who, when and how across the UK","authors":"C. Geagan ,&nbsp;A. Sandhu ,&nbsp;L. Bouquillon ,&nbsp;R. Conn ,&nbsp;D. Bindman ,&nbsp;J. Pattni ,&nbsp;C. Turner ,&nbsp;R. McDonald ,&nbsp;J. Alex ,&nbsp;S. Rodney ,&nbsp;R. Quinlivan ,&nbsp;M. Guglieri ,&nbsp;V. Straub","doi":"10.1016/j.nmd.2024.07.074","DOIUrl":"10.1016/j.nmd.2024.07.074","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by mutations in the gene that codes for dystrophin. Patients experience a gradual loss of muscle starting in childhood that usually leads to death in the late 20s. Whilst the physical impact is well documented, the psychological and neuropsychological impact of this condition on children and young people (CYP) with DMD and their families has been largely overlooked and is poorly understood. The objective of the survey was to acquire qualitative and quantitative information about approaches to and provision for mental health (MH) needs in CYP with DMD across the UK. To identify areas of good practice as well as gaps in service provision and variation and inequity in access to services which will inform approaches to service improvement. Professionals across the NorthStar network (consortium of all the UK neuromuscular paediatric centres) and parents/caregivers will be recruited using separate online surveys. Questions have been designed by the project team and cover a range of similar themes regarding psychosocial support allowing comparison across the groups. CYP with DMD and their parents/caregivers will be invited to separate focus groups or interviews to discuss their views on support for mental health in DMD. Results are in progress. We hypothesise that MH support for CYP and their carers will be identified as an essential component of care that should be offered in the neuromuscular clinic, as part of a broader interdisciplinary integrated approach. Understanding viewpoints from different stakeholders is essential in the early stages of this project to help guide future research ideas and clinical practice. Further engagement with CYP and parents/carers regionally and nationally is crucial to service development. This project will be part of the wider DMD Care UK project which aims to provide consensus and an evidence base for the highest standard of care for all aspects of DMD. This is leading to UK-wide care recommendations, referral pathways, prescription guidance and clinical practice guidelines. Our work will embed psychosocial care within multidisciplinary teams treating DMD throughout the UK.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.65"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423653","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}