Myopathy

Rationale: A long-term prospective natural history study in an unselected group of patients including clinical and functional outcome measures is lacking in both SELENON-related myopathy (SELENON-RM) and LAMA2-related muscular dystrophy (LAMA2-MD). Due to the promising ongoing preclinical trials, there is a high need to obtain natural history data in order to reach trial readiness for both diseases. With the extended LAST STRONG study, we aim to further analyze and expand our 1.5-year natural history data on SELENON-RM and LAMA2-MD to provide a detailed clinical description of the Dutch and Flemish cohort. This will enable a smooth transition towards implementation into clinical care and clinical trials that are expected to start within 5 years. Objective: (1) To collect 3- and 5-year natural history data in patients with SELENON-RM and LAMA2-MD. (2) Implementation of natural history data collection into clinical care and international guidelines, and reach trial readiness. Study design: This is an observational study. A variety of tests will be performed to get a full impression of the patient's abilities and disabilities (standard medical history, neurological examination, functional measurements, questionnaires, imaging, pulmonary assessment and accelerometry). The tests that the patient undergoes depend on the age/abilities/wishes. The tests are selected based on our previously performed 1.5-year natural history study in LAMA2-MD and SELENON-RM. Each participant will perform these measurements during the two scheduled visits at 3- and 5-year after the first visit during the LAST STRONG Study. Risk and benefit assessment: This study does not concern any product (medicinal product, food product or medical device). There is a small risk for minor injury, e.g. when a participant falls. However since the investigators use all functional tests using movements to which most participants are familiar (i.e. walking, transfers, etc.), the participant will be able to estimate his/her own risk. The investigators don't include tests in which they push participants to their physical limits. the investigators conclude that this study has a negligible risk. A benefit includes the possibility for participants to get a detailed analysis on their own health. Additionally, participants will contribute to the design of future clinical trials on possible treatment options.

This is an open-label, dose escalation study in patients with relapsed and refractory autoimmune diseases. Study drug, TI-0032-III injection, is composed of lipid nanoparticles (LNPs) targeting T cells that encapsulate circular RNA encoding the CD19 chimeric antigen receptor (CAR), which is a therapeutic biological product. It is clinically intended for the treatment of various relapsed and refractory B cell-related autoimmune diseases, such as systemic lupus erythematosus, sjögren's syndrome, systemic sclerosis, idiopathic inflammatory myositis, and antiphospholipid syndrome.

This study evaluates the safety and efficacy of YTS109 cells in adults with relapsed/refractory autoimmune diseases, such as Systemic Lupus Erythematosus (SLE), including LN and SLE-ITP, Sjogren's Syndrome, etc. Aproximately 18 patients aged 18-65 will receive a single infusion of YTS109 cells. The dose groups are set to commence at 3×10⁶ STAR -T cells/kg, employing a 3+3 escalation principle for dose titration. The primary objective of this study is to evaluate the safety of YTS109 cells therapy in treating recurrent/refractory autoimmune diseases, while the secondary objectives are to assess the efficacy of YTS109 cells as well as their pharmacokinetic and pharmacodynamic characteristics. The primary endpoint is observations of types, severity, and frequency of adverse events (AEs) and efficacy assessment. This single-arm, open-label trial will enroll patients across The First Affiliated Hospital of Anhui Medical University.

Background: Autoimmune diseases (AIDs) are a group of disorders in which the immune system mistakenly targets and attacks the body's own tissues, leading to tissue damage. Based on the sites of involvement, autoimmune diseases can be broadly classified into two categories: organ-specific autoimmune diseases, such as myasthenia gravis affecting the nervous system, type 1 diabetes mellitus involving the destruction of pancreatic islet cells, and autoimmune hepatitis targeting the liver; and systemic autoimmune diseases that affect multiple tissues and organs, reflecting an imbalance in the immune system, such as systemic lupus erythematosus（SLE）, Sjögren's syndrome（SS）, and systemic sclerosis（SSc）. Recently, the therapeutic advancements have been made in the management of AIDs. However, particularly the patients with relapsed/refractory, continue to face significant unmet clinical needs. CAR-T cell therapy has emerged as one of the innovative therapeutic modalities for autoimmune diseases, characterized by its controllable safety profile and durable therapeutic efficacy, warranting further clinical exploration and investigation in the future. YTS109 cell is a universal allogeneic STAR-T cell therapy targeting CD19, designed to efficiently eliminate B cells in patients with AIDs and mitigate autoimmune responses. Design: This is a Single-Center, Single-Arm, prospective exploratory clinical trial designed to evaluate the safety profile, preliminary therapeutic efficacy, and pharmacokinetic/pharmacodynamic (PK/PD) characteristics of YTS109 cell therapy in patients with relapsed/refractory autoimmune diseases. Approximately 6-12 patients aged 18-65 will receive a single infusion of YTS109 cells (1.5×10⁶ cells/kg). The primary endpoint is observations of types, severity, and frequency of adverse events (AEs) and efficacy assessment. This study was approved by the IRB of Chinese People's Liberation Army (PLA) General Hospital. (Approval Number: S2025-233-01), All participants provided written informed consent.

This study evaluates the safety and efficacy of YTS109 cells in adults with relapsed/refractory autoimmune diseases, such as Systemic Lupus Erythematosus (SLE), including LN and SLE-ITP, Sjogren's Syndrome, etc. Aproximately 18 patients aged 18-65 will receive a single infusion of YTS109 cells. The dose groups are set to commence at 3E6 STAR -T cells/kg, employing a 3+3 escalation principle for dose titration. The primary objective of this study is to evaluate the safety of YTS109 cells therapy in treating recurrent/refractory autoimmune diseases, while the secondary objectives are to assess the efficacy of YTS109 cells as well as their pharmacokinetic and pharmacodynamic characteristics. The primary endpoint is observations of types, severity, and frequency of adverse events (AEs) and efficacy assessment. This single-arm, open-label trial will enroll patients across Institute of Hematology \& Blood Diseases Hospital.

Lev is a brief, transdiagnostic, interprofessional intervention targeting health-related habits that is intended for several care settings. The main population intended is individuals with neurodevelopmental disorders or parents or close relations to children with disabilities. This study will therefore be open for participants recruited from several types of healthcare services in Sweden. Study 1: The feasibility trial investigates the following questions: Completion: How many participants that started Lev completed the intervention? What were the reasons for not not completing Lev? How many sessions did the participants complete? Lev includes screening (Lev-s), three sessions + one booster session. Level of acceptability: Was Lev perceived as creditable and satisfactory by healthcare workers and participants? Treatment credibility will be measured before Lev and after the last session for both participants and healthcare workers. Treatment satisfaction will be evaluated after each session and after the intervention is completed. Session evaluations will be done by both participants and healthcare workers. Do the intervention lead to adverse events? To what extent were individual goals met?

The aim of the present study is to establish a modified minimally invasive surgical technique for sinus floor augmentation with a residual bone height of 3-6mm. Hypothesis: The investigators expect that the present surgical technique allows to achieve an adequate implant bed of at least 10mm height after a healing period of 3-5 months. Further the modification of the technique enables a reduced patient stress level.

STUDY DESCRIPTION: This prospective natural history study seeks to characterize the clinical manifestations and course of Ryanodine Receptor 1 -related disorders (RYR1-RD). RYR1-RD include a wide range of rare congenital and adult-onset neuromuscular phenotypes that are typically slowly progressive. The study is observational and comprises a primary data collection phase (Years 1-3) and extended follow-up phase (Years 4-5), stratified into centralized (ambulatory) and decentralized (non-ambulatory) arms. During each phase, there will be one visit per year. The study will enhance the foundational knowledge of RYR1-RD and support clinical trial readiness. OBJECTIVE: Primary: Characterize phenotype and disease course over a three-year period Secondary: Characterize phenotype and disease course over an extended (2-year) period (total 5 years) Exploratory: 1. Investigate potential biomarkers of disease status and progression 2. Explore clinical meaningfulness thresholds for research assessments 3. Extract common data elements from existing medical records (real-world evidence) ENDPOINTS: Primary: Change from baseline to Year 3 in: Motor function and performance * Motor Function Measure (MFM) sub-domains (percent of maximum score) * Six-minute walk test (meters travelled with percent predicted) * Timed functional tests (ascend four stairs, descend four stairs, supine to stand) (seconds) * Grip and pinch strength (kg and percent predicted) * Performance of Upper Limb (PUL) * Accelerometry (wearable sensor) * Quantitative muscle assessment * Brooke and Vignos assessment Pulmonary function * Forced vital capacity (percent reference norm) * Forced expiratory volume at 1 second (percent reference norm) * Slow vital capacity (Liters) * Maximal voluntary ventilation (Liters) * Maximum inspiratory pressure (MIP) * Maximum expiratory pressure (MEP) Patient-reported outcomes * PROMIS-57 Profile (subscale and overall t-scores); adults - depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and satisfaction with participation in social roles * PROMIS Ped-25 Profile (subscale and overall t-scores); 8 - 17 y * PROMIS Parent Proxy 25 Profile - Fatigue, physical stress experiences, positive affect and wellbeing, psychological stress experiences, anxiety/fear, physical function, pain; 5 - 7 y * PROMIS Upper Extremity - Short Form 7a * PROMIS Pediatric Upper Extremity - Short Form 8a * PROMIS Parent Proxy Upper Extremity - Short Form 8a * Physical Activity Questionnaire for Children (PAQ-C); 8 - 13 y * Physical Activity Questionnaire for Adolescents (PAQ-A); 14 - 17 y * International physical activity questionnaire (IPAQ); adults Ophthalmology * Visual acuity * Dilated ophthalmology exam at baseline only * Extraocular motility assessment * Marginal reflex distance (Ptosis) * Optical Coherence Tomography * Ancillary testing, imaging, and repeat dilated exams as indicated, based on assessment and discretion of clinician Secondary: Change from baseline to Year 5 in: Motor function and performance * Motor Function Measure (MFM) sub-domains (percent of maximum score) * Six-minute walk test (meters travelled with percent predicted) * Timed functional tests (ascend four stairs, descend four stairs, supine to stand) (seconds) * Grip and pinch strength (kg and percent predicted) * Performance of Upper Limb (PUL) * Accelerometry (wearable sensor) * Quantitative muscle assessment * Brooke and Vignos assessment Pulmonary function * Forced vital capacity (percent reference norm) * Forced expiratory volume at 1 second (percent reference norm) * Slow vital capacity (Liters) * Maximal voluntary ventilation (Liters) * Maximum inspiratory pressure (MIP) * Maximum expiratory pressure (MEP) Patient-reported outcomes * PROMIS-57 Profile (subscale and overall t-scores); adults - depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and satisfaction with participation in social roles * PROMIS Ped-25 Profile (subscale and overall t-scores); 8 - 17 y * PROMIS Parent Proxy -25 Profile Fatigue, physical stress experiences, positive affect and wellbeing, psychological stress experiences, anxiety/fear, physical function, pain; 5 - 7 y * PROMIS Upper Extremity - Short Form 7a * PROMIS Pediatric Upper Extremity - Short Form 8a * PROMIS Parent Proxy Upper Extremity - Short Form 8a * Physical Activity Questionnaire for Children (PAQ-C); 8 - 13 y * Physical Activity Questionnaire for Adolescents (PAQ-A); 14 - 17 y * International physical activity questionnaire (IPAQ); adults Ophthalmology * Visual acuity * Dilated ophthalmology exam at baseline only * Extraocular motility assessment * Marginal reflex distance (Ptosis) * Optical Coherence Tomography * Ancillary testing, imaging, and repeat dilated exams as indicated, based on assessment and discretion of clinician Exploratory: Biomarkers Including but not limited to: * Plasma NAD plus, NADH * Plasma GSH, GSSG * Plasma cytokines * Serum creatine phosphokinase * Urine and plasma 15-F2t isoprostane * Urine 8OHdG * PBMC (Peripheral Blood Mononuclear Cell) * Near infrared spectroscopy (muscle tissue oxygenation) * Dixon MRI of lower extremity * Optional skin punch biopsy (fibroblast culture) * Muscle ultrasound * Electrical impedance myography (EIM)

Study Description: This study will explore the natural history and mechanisms of novel or known but incompletely characterized disorders of pyrimidine and purine metabolism (DPPMs). Eligible participants will be ascertained by identifying biochemical abnormalities in the levels of purines, pyrimidines and related compounds in body fluids, abnormal activity of enzymes, and/or identifying pathogenic variants in genes linked to purines and pyrimidine metabolism. We will collect participants DNA for genetic and genomic analyses, body fluids for biochemical analysis, blood and tissue samples for enzyme analysis, gastrointestinal samples for microbiome analysis. Some participants may undergo skin biopsy. Study subjects will be offered medical, laboratory, and imaging studies at the NIH Clinical Research Center consistent with the standards of care. Collected data will be analyzed to improve understanding of the natural history, develop statistical prediction models, identify and validate novel biomarkers. Objectives: Primary Objective: To describe features of novel and poorly characterized DPPMs. Secondary Objectives: To identify genomic, clinical, pharmacological, laboratory, and dietary factors associated with variable outcomes in subjects affected by DPPMs. Endpoints: Primary Endpoint: Identify genomic variants, laboratory parameters, image findings, microbiome variables, nutritional and medication history of DPPMs. Secondary Endpoints: Identify disease parameters associated with variable clinical outcomes (e.g., frequency of hospitalizations, survival, quality of life, function).

This is a Phase 1 open-label, multi-center safety and dose-escalation study of anito-cel\* in adult subjects with GMG (MGFA Grade 2 to 4a), in whom immunosuppressive therapy is clinically indicated in the judgement of the treating neurologist. The primary objective of this study is to assess the safety profile, including any DLT and identification of a MTD (if applicable), to support selection of the RP2D of anito-cel when administered to subjects with GMG. The study will have the following sequential phases: screening, enrollment (leukapheresis), pretreatment with lymphodepletion (LD) chemotherapy, treatment with anito-cel and follow-up. Optional bridging therapy is allowed at investigator discretion while anito-cel is being manufactured. Following a single infusion of anito-cel both safety and efficacy data will be assessed. The DLTs will be assessed in the first 28 days following anito-cel administration, and safety data will be collected throughout the study. \*Anitocabtagene autoleucel (anito-cel) drug product consists of autologous T cells that have been genetically modified ex vivo to express a D-domain Chimeric Antigen Receptor (CAR), followed by a cluster of differentiation 8 (CD8) hinge and transmembrane region that is fused to the intracellular signaling domains for 4-1BB and CD3ξ, that specifically recognizes B-cell maturation antigen (BCMA). The active substance of anitocabtagene autoleucel is CAR+ CD3+ T cells that have undergone ex vivo T-cell activation, gene transfer by replication-deficient lentiviral vector, and expansion.