Facioscapulohumeral Muscular Dystrophy (FSHD) Research This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

P316 Disability questionnaire of FSHD1 correlates with the in-person examination
Facioscapulohumeral muscular dystrophy (FSHD) is one of the common muscular dystrophies in adults. Once diagnosed, the patients tend to avoid visiting hospitals due to lack of effective treatment. So, it is difficult to track the current disability of the patients with FSHD. Here, we developed the questionnaire, which comprises 27 questions reflecting daily activities, and validated those questions with a manual muscle test (MMT). This is a prospective and cross-sectional study. The FSHD1 patients diagnosed by a Southern blotting were recruited from four different tertiary hospitals. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: J. Lee, J. Shin, I. Nishino, Y. Lee, Y. Kim Source Type: research

P314 A systematic literature review to assess the level of evidence in facioscapulohumeral muscular dystrophy
Facioscapulohumeral muscular dystrophy (FSHD) is a rare, debilitating disease for which there are no approved pharmacological interventions. As the disease progresses, patients lose upper limb function and mobility, which results in a decrease in the ability to perform activities of daily living and independence; patients often live with chronic pain. This systematic literature review (SLR) assessed the evidence base in FSHD.The SLR was conducted by searching PubMed, EMBASE and Cochrane Reviews databases for studies reporting on FSHD, with no limits on interventions, comparators, outcomes, study design or date of publicati...
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: L. Barnieh, R. Beckerman, H. Emich, K. Eichinger, A. Eldar-lissai Source Type: research

P313 Radiological and circulating biomarkers in facioscapulohumeral muscular dystrophy: a longitudinal study
As therapeutic options move into clinical trials for FSHD, the identification of circulating biomarkers of disease activity and progression is essential to facilitate the drug development process. This 24-month study combined analysis of muscle imaging and serum samples to investigate possible correlations between measures of radiological disease activity and progression and concentrations of circulating molecules. Consecutive adult FSHD patients were enrolled and followed up by clinical examination and upper girdle and lower limb muscle magnetic resonance imaging (MRI) every 12 months. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: S. Bortolani, M. Monforte, M. Pescatori, S. Ielpo, A. Palazzo, N. Mosca, E. Torchia, T. Tartaglione, E. Ricci, G. Tasca Source Type: research

P312 Quality of life and support needs in children and adolescents with facioscapulohumeral dystrophy, a qualitative study
Quality of life (QoL) in children w facioscapulohumeral dystrophy (FSHD) seems decreased. Little is known about factors influencing QoL in children with FSHD. Our objective is to describe which factors contribute to the QoL of children and adolescents with FSHD and to explore their support needs. We performed a qualitative study with individual age-appropriate semi-structured interviews assessing QoL in children and adolescents with FSHD and their parents. To characterize the cohort, quantitative data on QoL, pain, fatigue and participation were collected. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: J. Dijkstra, N. Rasing, E. Boon, E. Cup, S. Altena-Rensen, A. Lanser, B. van Engelen, A. Ramakers, C. Erasmus, N. Voermans Source Type: research

P311 Facioscapulohumeral muscular dystrophy European patient survey: assessing patient preferences in clinical trial participation  
This study aimed to explore the patient preferences of people with FSHD to ensure that clinical trials can be designed to include outcome measures that are relevant and important to patients. 1147 participants responded to an online survey, representing 26 countries across Europe and a range of disease severities. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: M. McNiff, S. Hawkins, B. Haase, J. Bullivant, T. McIver, O. Mitelman, N. Emery, G. Tasca, N. Voermans, J. Diaz-Manera Source Type: research

P310 Direct measure of D4Z4 repetition in FSHD1 patients by applying comprehensive BLAST using nanopore sequencing
Facioscapulohumeral muscular dystrophy (FSHD) is one of the common myopathies in adults. Shortness of D4Z4 below ten repeats in the 4qA allele is known to be pathogenic in FSHD type 1. However, the current genetic diagnosis, southern blot, is a laborious task requiring seven consecutive days. Here, we introduce a new diagnostic technique using long-read sequencing to measure D4Z4 repeats directly without any further manipulation. We enrolled four patients with FSHD1 confirmed by a Southern blot. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: J. Lee, H. Lee, S. Jeon, J. Bhak, J. Shin, I. Nishino Source Type: research

P309 EPI-321: A promising gene therapy for facioscapulohumeral muscular dystrophy (FSHD) targeting D4Z4 epigenome
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common types of muscular dystrophy with an annual incidence rate of about 1 in 10,000, affecting approximately 800,000 people globally. With no cure available, current therapeutic strategies only involve managing symptoms to improve overall quality of life. Stochastic (mis)expression of disease-causing protein, DUX4, in muscle leads to slow and progressive muscle degeneration/wasting through activation of apoptotic and other downstream pathways, which makes the development of cure difficult. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: A. Adhikari, S. Boregowda, H. Zheng, O. Aguirre, A. Norton, X. Yang, T. Luong, D. Ko, L. Smith, R. Swan, B. Jiyarom, F. Jiang, T. Daley, D. Hart, Y. Liu, A. Collin Source Type: research

P308 Development of a new DUX4-responsive reporter mouse
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder affecting approximately 870,000 people worldwide. It is a progressive muscle wasting disease with symptoms typically starting in early adulthood. There is currently no treatment for FSHD, though the last few years have seen an increase in both the drug discovery pipeline and the FSHD clinical trial network. One hurdle for many of these studies is the imperfect animal models that must be used to establish efficacy.Several FSHD mouse models are available, including our lab's TIC-DUX4 model. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: L. Wallace, J. Camp, N. Taylor, S. Harper Tags: FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY Source Type: research

P51 Phase 1/2 study to evaluate AOC 1020 for adult patients with facioscapulohumeral muscular dystrophy: FORTITUDE trial design
The aim of the study is to evaluate the safety and tolerability of single and multiple ascending doses of AOC 1020 in participants with FSHD. FSHD is a rare, progressive, often asymmetric, genetic disease caused by aberrant expression of the transcription factor DUX4 in skeletal muscle, leading to a series of downstream events that result in degeneration and wasting. Strategies targeting DUX4 expression in skeletal muscle of individuals with FSHD via oligonucleotides are promising therapeutic approaches. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: A. Halseth, E. Ackermann, T. Brandt, C. Chen, H. Cho, M. Stahl, K. DiTrapani, S. Hughes, R. Tawil, J. Statland Source Type: research

Psychosocial functioning in patients with altered facial expression: a scoping review in five neurological diseases
CONCLUSIONS: This review showed that patients with altered facial expression in four of five included neurological diseases had reduced psychosocial functioning. Future research recommendations include studies on observers' judgements of patients during social interactions and on the effectiveness of compensation strategies in enhancing psychosocial functioning.PMID:37752723 | DOI:10.1080/09638288.2023.2259310 (Source: Disability and Rehabilitation)
Source: Disability and Rehabilitation - September 27, 2023 Category: Rehabilitation Authors: Nathani ël B Rasing Willianne van de Geest-Buit On Ying A Chan Karlien Mul Anke Lanser Corrie E Erasmus Jan T Groothuis Judith Holler Koen J A O Ingels Bart Post Ietske Siemann Nicol C Voermans Source Type: research

The transcription factor DUX4 orchestrates translational reprogramming by broadly suppressing translation efficiency and promoting expression of DUX4-induced mRNAs
We report that translation initiation and elongation factors are disrupted downstream of DUX4 expression in human myoblasts. Genome-wide translation profiling identified mRNAs susceptible to DUX4-induced translation inhibition, including those encoding antigen presentation factors and muscle lineage proteins, while DUX4-induced mRNAs were robustly translated. Endogenous expression of DUX4 in human FSHD myotubes and cancer cell lines also correlated with reduced protein synthesis and MHC-I presentation. Our findings reveal that DUX4 orchestrates translational reprogramming by suppressing the cellular proteome while maintain...
Source: Cancer Control - September 25, 2023 Category: Cancer & Oncology Authors: Danielle C Hamm Ellen M Paatela Sean R Bennett Chao-Jen Wong Amy E Campbell Cynthia L Wladyka Andrew A Smith Sujatha Jagannathan Andrew C Hsieh Stephen J Tapscott Source Type: research

The transcription factor DUX4 orchestrates translational reprogramming by broadly suppressing translation efficiency and promoting expression of DUX4-induced mRNAs
We report that translation initiation and elongation factors are disrupted downstream of DUX4 expression in human myoblasts. Genome-wide translation profiling identified mRNAs susceptible to DUX4-induced translation inhibition, including those encoding antigen presentation factors and muscle lineage proteins, while DUX4-induced mRNAs were robustly translated. Endogenous expression of DUX4 in human FSHD myotubes and cancer cell lines also correlated with reduced protein synthesis and MHC-I presentation. Our findings reveal that DUX4 orchestrates translational reprogramming by suppressing the cellular proteome while maintain...
Source: PLoS Biology: Archived Table of Contents - September 25, 2023 Category: Biology Authors: Danielle C. Hamm Source Type: research

Autosomal dominant in cis D4Z4 repeat array duplication alleles in facioscapulohumeral dystrophy
AbstractFacioscapulohumeral dystrophy (FSHD) has a unique genetic aetiology resulting in partial chromatin relaxation of the D4Z4 macrosatellite repeat array on 4qter. This D4Z4 chromatin relaxation facilitates inappropriate expression of the transcription factor DUX4 in skeletal muscle. DUX4 is encoded by a retrogene that is embedded within the distal region of the D4Z4 repeat array. In the European population, the D4Z4 repeat array is usually organized in a single array that ranges between 8 and 100 units. D4Z4 chromatin relaxation andDUX4 derepression in FSHD is most often caused by repeat array contraction to 1 –10 u...
Source: Brain - September 13, 2023 Category: Neurology Source Type: research

Whole exome sequencing highlights rare variants in CTCF, DNMT1, DNMT3A, EZH2 and SUV39H1 as associated with FSHD
Discussion: Our results support FSHD pathomechanism being complex with a multigenic contribution by several known (SMCHD1, DNMT3B, LRIF1) and possibly other candidate genes (CTCF, DNMT1, DNMT3A, EZH2, SUV39H1) to disease penetrance and expressivity. Our results further emphasize the importance of extending the analysis of molecular findings within the proband’s family, with the purpose of providing a broader framework for understanding single cases and allowing finer genotype-phenotype correlations in FSHD-affected families. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - August 22, 2023 Category: Genetics & Stem Cells Source Type: research