Neuromuscular Disorders最新文献

{"title":"213P Sensitivity to change of the motor function measure (MFM) in myotonic dystrophy type 1","authors":"S. Ribault ,&nbsp;P. Rippert ,&nbsp;G. Bassez ,&nbsp;T. Duong ,&nbsp;C. Vuilllerot","doi":"10.1016/j.nmd.2024.07.064","DOIUrl":"10.1016/j.nmd.2024.07.064","url":null,"abstract":"<div><div>Myotonic dystrophy type 1 (DM1) is a hereditary multisystemic disease characterized by progressive muscle wasting, heart conduction abnormalities, early-onset cataract, and endocrinological disorders. It is caused by a non-coding CTG repeat expansion in the DMPK gene. With new therapeutic advancements and ongoing clinical trials focusing on siRNA, antisense oligonucleotides or gene therapy, there is an imperative to identify a suitable clinical outcome to assess motor function in DM1. The Motor Function Measure is a 3-dimensional quantitative scale (D1: standing/transfers, D2: Proximal/axial, D3: Distal) designed to monitor motor function in patients with neuromuscular diseases encompassing the spectrum of the disease regardless disease severity or functional level. This is a multicentric retrospective review of adults and children with a genetic diagnosis of DM1. Included subject were male or female DM1 patients with the availability of at least 2 MFM32 scores at 1 year. MFM32’s mean slope of change and standard response mean (SRM) were calculated. 343 subjects were included. At the first MFM mean age was 36.3 years (+/- 16.1, min: 6.1yo; max: 71.8yo), and mean MFM32 scores were 69.1%+/-25.1, 91.9%+/-9.1, 90.8.1%+/-8.4, and 82.4%+/-13.8 for D1, D2, D3 and Total score respectively. Average time between first and last assessments was 5.1 years (+/- 3.6, min: 1 y; max: 15.9yo). MFM32’s yearly mean slope of change was -2.25% (+/-3.86) for D1, -1.09% (+/-3.50) for D2, -0.54% (+/-2.95) for D3, -1.44 (+/-2.46) for total score. SRM was -0.58 for D1, -0.31 for D2, -0.18 for D3, -0.59 for total score. Understanding the change over time in a natural history cohort is important to understand the impact of change against a changing disease landscape. We showed MFM32’s responsiveness to change most relevant in the standing and transfer domain (D1) and MFM total score than the more proximal or distal domains.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.55"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423719","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":"363P A cross-sectional survey upper limb functional using PUL 2.0 at large clinical centers and registries in patients with Duchenne muscular dystrophy","authors":"G. Coratti ,&nbsp;E. Niks ,&nbsp;M. van der Holst ,&nbsp;C. Tian ,&nbsp;E. Mercuri ,&nbsp;F. Muntoni ,&nbsp;L. Servais ,&nbsp;S. Ward","doi":"10.1016/j.nmd.2024.07.100","DOIUrl":"10.1016/j.nmd.2024.07.100","url":null,"abstract":"<div><div>Upper limb function is a critical determinant of quality of life for patients with Duchenne Muscular Dystrophy (DMD) who have lost the ability to walk. However, the majority of clinical trials assessing new therapeutic agents have focused on ambulant patients with DMD. The reasons for this gap are multi-fold but are due in part to the consensus for using the PUL 2.0 assessment as a primary endpoint being more recent. This study is a cross-functional survey of upper limb functional assessments focused on the large clinical centers and clinical registries led by cTAP collaborators and determined i) the number of patients with PUL 2.0 assessments, ii) frequency of evaluation, iii) functional characteristics of patients at baseline, and iv) the trigger for initiating PUL 2.0 evaluation. Most centers assessed upper limb function at 6-month intervals. The number of patients and patient visits at each center were, respectively: Italian Group (341,1628), CCHMC (256, 1145), GOSH (84, ∼240), Leiden University Medical Center (LUMC)(81, 278) and NMCL (25, &gt;100). Mean PUL 2.0 entry score was 29.9 (SD 12.5) and 30.93 (SD 5.1) in the Italian Group and LUMC respectively; corresponding age at entry was (12.2 (SD 6.23) and 11.75 (SD 12.1). The number of patients with 5 or more follow-up assessments was 88 at 6 monthly intervals for the Italian Group and 28 at 12-month intervals for LUMC. Assessment of ambulatory function across centers was largely coherent, while protocols to assess bone health, cardiac function, and pulmonary function were less consistent. The results of this study will aid drug developers in better understanding the characteristics of this patient population, a pre-requisite step to designing clinical trials that can yield definitive assessment and therapeutic efficacy. It also highlights the importance of collecting consistent and high-quality real-world data in rare diseases.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.91"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423994","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":"365P Duchenne video assessment 2.0 scorecard performance: evaluation of inter-item and inter-scorecard relationships","authors":"M. Contesse ,&nbsp;A. Sapp ,&nbsp;C. Zigler ,&nbsp;W. Chen ,&nbsp;J. Marshall ,&nbsp;G. Gensler ,&nbsp;C. Brown ,&nbsp;R. Barnes ,&nbsp;D. King ,&nbsp;S. Wilson ,&nbsp;M. Leffler","doi":"10.1016/j.nmd.2024.07.102","DOIUrl":"10.1016/j.nmd.2024.07.102","url":null,"abstract":"<div><div>People with Duchenne muscular dystrophy (DMD) compensate for muscle weakness by changing their movement patterns. The Duchenne Video Assessment (DVA) is a home-based tool that measures ease of movement through identification of movement compensations. The DVA directs caregivers to video record patients attempting specific movement tasks (e.g., Climb 5 Stairs) at home using a mobile application. DVA 2.0 comprises 18 movement tasks and assesses patients at any disease stage through a subset of tasks relevant to their functional group. DVA-certified physical therapists rate the videos using validated scorecards with clinically meaningful compensatory movement criteria (“items”). ARISE is a longitudinal, observational study of 150 participants with DMD aged 2 and older to evaluate the measurement properties of DVA 2.0 over 24 months. Using baseline data, we evaluated the relationships among DVA 2.0 scorecards and criteria to confirm that they contribute distinct information to the outcome. We assessed the correlation between each criteria pair, and correlation type (polychoric, rank-biserial, Phi) was determined by number of levels within compared criteria. We assessed inter-scorecard relationships using a Spearman correlation matrix. Criteria and scorecards with very strong correlations (&gt;|0.9|) were explored for content overlap and considered for removal. All scorecards and all but one pair of criteria had correlations below the threshold. One pair of criteria for Reach Across the Table to Grab a Cell Phone was above the threshold (rpc = 0.971), but 15% of the study population differed in severity level for the two criteria. Since expert consensus previously established the clinical meaningfulness of each criterion and maintaining both criteria provides additional information for 15% of the study population, both were retained. The results confirm that all DVA 2.0 criteria and scorecards contribute distinct information about the ease of movement of people with DMD.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.93"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423996","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":"278P Mapping human skeletal muscle enhancers to increase rates of genetic diagnosis","authors":"R. Taylor ,&nbsp;J. Taylor ,&nbsp;E. Denisenko ,&nbsp;M. Jones ,&nbsp;J. Clayton ,&nbsp;N. Laing ,&nbsp;A. Forrest ,&nbsp;H. Alinejad-Rokny ,&nbsp;G. Ravenscroft","doi":"10.1016/j.nmd.2024.07.096","DOIUrl":"10.1016/j.nmd.2024.07.096","url":null,"abstract":"<div><div>Despite the identification of almost 600 disease genes for neuromuscular disorders, only 30-50% of affected individuals receive a genetic diagnosis following diagnostic screening via targeted gene panels or clinical exomes. For a subset of those patients who do not receive a genetic diagnosis, the disease causing variant may be located in the 98% of the human genome that is non-coding. Approximately 20-40% of the non-coding genome has a regulatory function, dictating when in development, in which tissues, and at what level our coding genes are expressed. Genetic variation in regulatory regions has been shown to cause Mendelian disease by reducing or abolishing the expression of the corresponding coding gene. However, regulatory regions are not routinely screened because we do not know where these regions are in the genome. In order to differentiate the functional non-coding variants from the vast number of benign non-coding variants we need to know which regions of the genome regulate gene expression in the tissues relevant to the disease. We have approached this systematically with a focus on identifying the distal regulatory elements involved in expression of skeletal muscle disease genes. We have mapped enhancer-promoter interactions in healthy adult human skeletal muscle tissue (n=3 unrelated donors) by creating genome-wide chromatin conformation capture libraries at 5kb resolution using the Dovetail Genomics OMNI-C workflow. We also profiled human skeletal muscle regulatory regions (n=3 donors) by performing ChIP-seq for histone modifications associated with enhancers (H3K4me1) and promoters (H3K4me3), as well as the chromatin architecture protein CTCF. These data were integrated with human skeletal muscle snRNA-seq (n=4 donors) and various public datasets associated with skeletal muscle relevant phenotypes. We have created a high-quality map of human skeletal muscle enhancers and their linked promoters and show that this map is capable of identifying statistically significant interactions between key muscle gene promoters with both known and novel distal regulatory elements. Our hope is that this map can now be used as a screening tool to prioritise non-coding sequence variants that are likely to be causal for Mendelian muscle diseases.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.87"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424006","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":"210P Advancing upper limb motor function evaluation in Duchenne muscular dystrophy and spinal muscular atrophy via kinematic parameterization with the wearable device “ArmTracker”","authors":"D. Natera De Benito ,&nbsp;A. Favata ,&nbsp;J. Expósito-Escudero ,&nbsp;R. Gallart ,&nbsp;O. Moya ,&nbsp;S. Roca ,&nbsp;A. Marzabal Gatell ,&nbsp;L. van Noort ,&nbsp;C. Ortez ,&nbsp;C. Torras ,&nbsp;A. Nascimento ,&nbsp;J. Medina-Cantillo ,&nbsp;R. Pàmies Vilà ,&nbsp;J. Font-Llagunes","doi":"10.1016/j.nmd.2024.07.061","DOIUrl":"10.1016/j.nmd.2024.07.061","url":null,"abstract":"<div><div>Assessing upper limb motor function in Duchenne Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA) traditionally relies on the Performance of Upper Limb (PUL) and Revised Upper Limb Module (RULM) scales, respectively. While considered gold standards, using these scales in isolation presents some challenges, notably in capturing subtle changes in motor function over time or in response to treatments. Inertial Measurement Units (IMUs) are inertial sensors that provide objective and quantifiable movement data. We hypothesize that integrating IMU measurements into these scales could provide complementary data for a more comprehensive assessment of motor function in individuals with neuromuscular diseases. Ten children with DMD (aged 12-17, Brooke score 2-5), 10 children with SMA (aged 6-13, Brooke score 2-5), and 6 healthy control children (aged 5-17, Brooke score 1) performed the PUL and RULM scales while wearing the ArmTracker device, equipped with 7 IMUs (Xsens Dot, Xsens Technologies) placed on the back of the hands, forearms, arms, and torso. Each IMU provided quaternion data. A sensor-to-segment calibration process was conducted with subjects seated in a chair with forearms resting on a table. Photographs were taken in frontal and lateral planes during calibration, and this visual information was integrated with IMU data to enhance calibration accuracy. Euler angles YZ'Y’’ for the shoulder, and ZX'Y’’ for the elbow and wrist were utilized. Maximum reachable area of hands, workspace area, and range of motion of shoulder, elbow, and wrist were evaluated and correlated with motor function scale scores using the Spearman correlation coefficient. Workspace area was normalized by the maximum achievable area by individuals (in %). We found significant correlations between the workspace area of upper limbs, notably on the frontal plane, and the scores of both the PUL and RULM. Additionally, significant correlations were observed between the scores of both motor function scales and the range of motion (ROM) of the shoulder. Furthermore, a correlation matrix analyzing the angles of the three primary upper limb joints revealed compensation patterns, which proved particularly valuable in identifying compensatory movements during the shoulder abduction task within the scales. Employing inertial sensors during the administration of functional motor scales in individuals with neuromuscular diseases yields valuable variables for assessing motor function, with particular interest in workspace area of the upper limbs and ROM of the shoulder. These and other variables are currently under further investigation within the same cohort of individuals who have undergone evaluations at home and school spanning four days utilizing the ArmTracker. This ongoing research aims to ascertain the system's potential for conducting assessments at home and assessing real-life movements in everyday scenarios.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.52"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423233","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":"208P Are people living with neuromuscular disorders in the north of England satisfied with National Health Service wheelchair service provision?","authors":"J. Michell-Sodhi,&nbsp;D. Moat,&nbsp;T. Dias,&nbsp;J. Mason,&nbsp;E. Robinson,&nbsp;M. Schiava,&nbsp;E. Barr,&nbsp;C. Bolano,&nbsp;S. Doaa,&nbsp;K. Wong,&nbsp;E. Maha,&nbsp;G. Emma,&nbsp;G. Michela,&nbsp;M. Michelle,&nbsp;G. Tasca,&nbsp;J. Diaz-Manera,&nbsp;M. James,&nbsp;V. Straub,&nbsp;C. Marini-Bettolo,&nbsp;R. Muni-Lofra","doi":"10.1016/j.nmd.2024.07.059","DOIUrl":"10.1016/j.nmd.2024.07.059","url":null,"abstract":"<div><div>People living with neuromuscular disorders (NMD) often describe weakness, reduced mobility, falls, pain and fatigue as factors requiring mobility support with a wheelchair (WC). The timely and appropriate provision of mobility aids, including WC can help manage symptoms and improve quality of life for both patient and care givers. Optimising WC provision is essential in facilitating independence in functional ability, participation and activities of daily living. This is particularly relevant for those who are reliant on powered wheelchair (PWC) provision during waking hours to enable independent mobility. The specific WC prescription needs of persons with NMD are not well documented. Within the UK, regional variations in WC provision exist leading to disparity and dissatisfaction with the provided service. The aim of this project was to understand National Health Service WC provision and level of satisfaction with WC prescription in our clinical cohort. We surveyed 149 wheelchair users with NMD living in the North of England between 2019-2023. Respondents were aged 3-81 years, with a mean age 33 years. 42 respondents were paediatric. Diagnoses included Duchenne muscular dystrophy (45), spinal muscular atrophy (22), myotonic dystrophy (14), limb girdle muscular dystrophy (12), and Becker muscular dystrophy (13). 82 respondents used PWC, 49 a manual WC (MWC) and 17 power-assisted MWC. A third of respondents felt that their needs were not met by their current WC prescription. 15% of respondents reported delay in WC provision. This survey highlights concern at current practises in WC provision in the North of England and the need to determine evidence-based best practice guidelines for WC prescription for persons with NMD more generally.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.50"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423395","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":"WMS 2024 Full Programme","authors":"","doi":"10.1016/S0960-8966(24)00952-0","DOIUrl":"10.1016/S0960-8966(24)00952-0","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104456"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423397","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":"123P The difficult path to diagnosis of the patient with spinal muscular atrophy","authors":"C. Bolano Diaz ,&nbsp;M. Morosini ,&nbsp;F. Chloca ,&nbsp;L. Mesa ,&nbsp;A. Jauregui ,&nbsp;L. Pirra ,&nbsp;G. Vazquez ,&nbsp;D. Flores ,&nbsp;A. Dubrovsky","doi":"10.1016/j.nmd.2024.07.030","DOIUrl":"10.1016/j.nmd.2024.07.030","url":null,"abstract":"<div><div>News treatments make early diagnosis of spinal muscular atrophy (SMA) critical. The objective of this study is to analyse the different factors that influence delay in diagnosis. Patients with a molecular diagnosis of types I, II, and III SMA were included. Several parameters were studied, such as age at onset of first sign, what sign it was, and the time from recognition of first sign to confirmed diagnosis. Neurologists specialized in SMA conducted interviews, supported by the review of medical records when deemed necessary. A total of 112 patients were interviewed. SMA I n = 40, SMA II n = 48, SMA III n = 24. The median age in months at the time of reporting the first sign was SMA I: 1.5 (R: 0–7), SMA II: 9 (R: 2–20), SMA III: 18 (R: 8–180). In all subtypes, first signs were identified by parents from 75% to 85% of the times. The top-3 detected signs were: SMA I: hypotonia (38.5%), developmental delay (33.3%), feeding difficulties (17.9%); SMA II: inability to stand (23%), inability to walk unaided (23%), proximal weakness (23%); SMA III: frequent falls (50%), unsteady gait (20.8%), developmental delay (16.7%). The median time from first sign to first medical consultation was less than a month in all 3 types. The SMN genetic study was requested by the healthcare professional during the first consultation in 22.5% of SMA I patients, 16.7% of SMA II patients and in none of the SMA III patients. The median time in months, from first sign to confirmed molecular diagnosis in SMA I was: 2 (R: 0–11), in SMA II: 10 (R: 3–46), in SMA III: 31.5 (R: 4–288). There is a significant delay in SMA diagnosis mainly related to the absence of clinical suspicion. The delay is shorter in SMA I and longer in SMA III. Other factors include deficiencies in the health care system.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.21"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423429","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":"130P Real-life outcome data on Risdiplam therapy for spinal muscular atrophy","authors":"R. Lavi ,&nbsp;L. Sagi ,&nbsp;S. Katzenellenbogen ,&nbsp;A. Shtamler ,&nbsp;A. Weizman ,&nbsp;I. Opincariu ,&nbsp;A. Fattal-Valevski","doi":"10.1016/j.nmd.2024.07.037","DOIUrl":"10.1016/j.nmd.2024.07.037","url":null,"abstract":"<div><div>Risdiplam is an orally administered novel small molecule approved for the treatment of spinal muscular atrophy (SMA), a rare and debilitating neuromuscular disorder. Risdiplam acts as a survival motor neuron (SMN) 2 splicing modifier, promoting the production of functional SMN protein, which is crucial for motor neuron survival and function. By increasing SMN protein levels, risdiplam compensates for the deficiency caused by SMN1 gene mutations, the underlying genetic cause of SMA. We collected the clinical outcome data of all individuals with SMA treated with risdiplam at the SMA clinic in a large tertiary hospital. The study participants included 22 individuals who received risdiplam between 5 months and 24 years of age (median age 15 years, interquartile range [IQR] 12-21) and whose median follow-up duration was 16 ([IQR] 9.3-19.1) months. Of these patients, 18 were previously treated with intrathecal nusinersen and 4 patients were treatment naive. Compared to baseline, in SMA type 1 patients, Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores were stable or slightly increased by a median of 0.4 points at last follow-up, while in SMA types 2-3 patients Hammersmith Functional Motor Scale Expanded (HFMSE) scores showed a mild increase by a median of 2 points at last follow-up and Revised Upper Limb Module (RULM) scores showed an increase of 1 point. No changes in ventilatory status or bulbar function were noted during risdiplam follow-up. Five out of 22 patients had mild adverse effects, including headache, vomiting, nausea and rash which resolved within days. Overall, risdiplam was well tolerated, easy to handle and led to stable or slightly improved motor function outcomes in SMA patients.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.28"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423493","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":"274P Generation of cardiac organoids from DuchenneMuscularDystrophy patient-derived induced pluripotent stem cells: a novel approach to understanding cardiomyopathy","authors":"M. Przymuszała,&nbsp;J. Stępniewski,&nbsp;U. Florczyk-Soluch,&nbsp;J. Dulak","doi":"10.1016/j.nmd.2024.07.092","DOIUrl":"10.1016/j.nmd.2024.07.092","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is a progressive muscle disease caused by mutations in the dystrophin gene. Cardiomyopathy is the leading cause of death in DMD patients, but the exact mechanisms underlying it remain unclear. Due to the limitations of animal models, patient-derived human models need to be developed to investigate cardiac pathophysiological mechanisms better. Hence, 3D human cardiac organoids (hCOs) are designed to more closely resemble the structural and functional properties of the human heart than traditional 2D cell cultures or animal models. For this purpose, we generated DMD patient-derived induced pluripotent stem cells (hiPSC) and corrected DMD mutation with CRISPR/Cas9 gene editing, establishing isogenic control lines. Healthy controls and CRISPR/Cas9 edited cells with introduced DMD gene exon 50 deletion were also sources for these cell types. Under specified culture conditions, these stem cells differentiate into various cardiac cell types, including cardiomyocytes (CM), endothelial cells (EC), and cardiac fibroblasts (CF). We affirmed the presence of specific markers (troponin T for CM, DDR2 for CF, and CD31 and VE-cadherin for EC), indicating successful differentiation. Self-aggregation of CM, CF, and EC at controlled ratios (CM: 75%, CF: 15%, EC: 15%) resulted in the formation of 3D cardiac organoids. Overall, we successfully generated cardiac organoids from hiPSCs derived from DMD patients, healthy donors, and isogenic control samples, which will be used to understand the mechanisms of DMD cardiomyopathy further. Grants support: National Science Centre: MAESTRO 2018/30/A/NZ3/00412.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.83"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423508","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}