P139 Correlation and validation of the North Star Ambulatory Assessment, timed test and motor function measure centiles for boys with Duchenne muscular dystrophy
There is significant heterogeneity in the North Star Ambulatory Assessment (NSAA) trajectories of boys with DMD, which may present a challenge for clinical care and development of clinical trials. Centiles quantify the cross-sectional variability in cohorts, are easily interpretable for patients and parents, and have been described for the Motor Function Measure (MFM) in boys both on and off corticosteroids (CS). We used the NorthStar Database to develop NSAA, Rise from Floor (RFF) and 10m Walk (10MWR) centiles-for-age for boys with DMD on CS. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: E. Milev, G. Stimpson, M. van der Holst, A. Wolfe, E. O'Reilly, A. Manzur, E. Niks, S. Houwen-Opstal, G. Baranello, F. Muntoni Source Type: research
P140 Predicting long-term trajectories of the North Star Ambulatory Assessment (NSAA) total score in Duchenne muscular dystrophy (DMD): an updated model
The NSAA is a widely used endpoint in DMD trials. Accurately predicting average NSAA total score trajectories is important for contextualizing the outcomes of novel therapies, especially over longer-term (>18 months) follow-up when placebo controls are infeasible. Expanding on a previous study, we used longitudinal data for a broadened population of boys with DMD who were initially ambulatory, aged 4 to (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: F. Muntoni, J. Signorovitch, N. Goemans, A. Manzur, N. Done, G. Sajeev, J. Li, H. Akbarnejad, A. Sharma, E. Niks, L. Servais, V. Straub, I. de Groot, S. Ward, C. McDonald Source Type: research
P141 Concordance of patient-reported outcomes measurement information system (PROMIS) questionnaires between caregivers and children with DMD
PROMIS includes patient-reported outcomes that quantify the impact of disease on physical, social, or cognitive function. While self-reporting is considered the gold standard, caregivers frequently report on behalf of patients in many disease states, including Duchenne muscular dystrophy (DMD). PROMIS Parent Proxy (PP) questionnaires are being used in DMD studies, with caregivers rating their child's functional ability. Agreement between caregiver and child on the PROMIS Mobility and Upper Extremity (UE) questionnaires remains largely unknown for the DMD community. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: I. Audhya, S. Patel, C. LeReun, L. Alfano, N. Reash, M. Iammarino, L. Lowes Source Type: research
P142 Accurate translation from Performance of Upper Limb (PUL) version 1.2 to 2.0 in Duchenne muscular dystrophy (DMD): a machine learning algorithm
The Performance of Upper Limb (PUL) module measures upper limb motor performance in ambulant and non-ambulant DMD. Two versions of the PUL exist: the originally developed version (PUL 1.2) and a revised version (PUL 2.0). While PUL 2.0 is currently in broader use in clinical trials and practice, prior studies contain extensive historical data on PUL 1.2. A cross-walk between PUL 1.2 and PUL 2.0 is needed to make full use of historical data, e.g., for contextualization of outcomes in clinical trials and across periods of natural history. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: G. Coratti, E. Mercuri, G. Sajeev, A. Zhang, S. Ward, M. Pane, B. Vilma, J. Signorovitch Source Type: research
P143 Centiles by age for the North Star ambulatory assessment and the associated timed items in glucocorticoid treated boys with Duchenne muscular dystrophy
Clinical heterogeneity in motor function trajectory in boys with Duchenne Muscular Dystrophy (DMD) represents a significant hurdle to clinical monitoring. With this study we present the centiles by age for the North Star Ambulatory Assessment (NSAA), 10m walk/run (10MWR) and rise from floor (RFF) in corticosteroids (CS) treated boys with DMD, between 5 and 16 years. Participants were included from the NorthStar registry if they had genetically confirmed DMD, had initiated CS and were not enrolled in a clinical trial. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: G. Stimpson, D. Ridout, A. Wolfe, E. Milev, E. O'Reilly, A. Manzur, T. Cole, F. Muntoni, G. Baranello, NorthStar Network Source Type: research
P144 Digital outcome captures longitudinal degradation of upper-limb function in non-ambulant patients affected by neuromuscular disorders
Precise upper limb function quantification is challenging but essential to judge efficacy of treatments for patients living with neuromuscular disorders. Lack of robust motor function endpoints has limited the number of clinical programs in this population and thus the access to innovative medication. The need for improving current outcomes and exploring innovative approaches, like wearable devices or video-based home assessment is consensual in the community. For ambulant patients affected by Duchenne muscular dystrophy (DMD), the EMA has recently qualified the first digital outcome as a primary endpoint in clinical trial...
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: L. Bancel, A. Tricot, A. Gu érin, D. Eggenspieler, C. Lilien, M. Poleur, L. Servais Source Type: research
P145 Analysis of the natural evolution of SV95C in ambulant patients with Duchenne muscular dystrophy
The progressive nature of functional loss in Duchenne Muscular Dystrophy (DMD) is well established and routinely characterised in clinic using assessments such as the North Star Ambulatory Assessment and the Six Meter Walk Test. The trajectory of functional loss depends on the patient's age and baseline functional ability. There is a need to better characterise the trajectory of disease progression in order to try to predict disease evolution and optimise patient care. Stride Velocity at the 95th Centile (SV95C) is a novel clinical outcome measure that is captured during normal daily living using wearable technology and re...
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: M. Rogers, S. Motola, D. Eggenspieler, M. Poleur, G. Parinello, D. Lozeve, A. Danon, L. Szabo, K. Aragon-Gawi ńska, A. Potulska-Chromik, N. Butoianu, C. Anghelescu, Mirea, D. Osredkar, E. Vrščaj, T. Golli, J. Haberlova, S. Kodsy, A. Salah, P. Strijbos Source Type: research
P146 A clinical trial simulation tool to accelerate trial design in DMD: description of the traphical user interface features and applications
Duchenne muscular dystrophy (DMD) is a rare, fatal, X linked, muscle wasting, and progressive disease that predominantly affects boys but has been shown to manifest in some female carriers. Despite recent progress in the drug development pipeline, trial design for DMD remains difficult due to challenges intrinsic to the nature of the DMD population and the limited understanding in rate of change of endpoints in given populations. The Duchenne Regulatory Science Consortium (D-RSC) at Critical Path Institute (C-Path), has developed a model-based clinical trial simulation (CTS) platform based on a series of quantitative model...
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: R. Belfiore-Oshan, V. Aggarwal, J. Wilk, M. Pauley, D. Corey, K. Romero, C. Hovinga, T. Martinez, K. Lingineni, D. Yoon, J. Morales, S. Kim Source Type: research
P147 Six-year long-term safety and efficacy of Golodirsen in patients with DMD vs mutation-matched external controls
Golodirsen is FDA approved for the treatment of Duchenne muscular dystrophy (DMD) in patients with exon 53 skip-amenable mutations. Results from Study 4053-101 (NCT02310906) and the open-label extension (OLE) 4045-302 (NCT03532542) evaluating the safety and efficacy of golodirsen treatment up to ∼6y in patients with progressive disease deterioration are described. Post hoc analyses comparing ambulatory and pulmonary function of golodirsen-treated patients with matched (including age, mutation, steroid use) external controls (EC) were performed. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: F. Muntoni, A. Seferian, V. Straub, M. Guglieri, L. Servais, E. Wilk-Durakiewicz, X. Ni, P. Gao, M. Hu, J. Iff, L. Hill, I. Sehinovych, L. Orogun, E. Mercuri Source Type: research
P148 Analysis of upper limb functional outcomes in a single centre paediatric cohort of non-ambulatory patients with Duchenne muscular dystrophy
There is limited knowledge of disease course in the nonambulatory phase of Duchenne muscular dystrophy (DMD), as well as of efficacy of glucocorticosteroid (CG) therapy in this population, in particular on upper limb function. Here we present analysis of upper limb function in non-ambulant paediatric DMD patients seen at Great Ormond Street Hospital, London UK, from October 2019 to date. We analysed functional status by measuring Performance of Upper Limb Module for DMD 2.0 (PUL) and Egen Klassifikation Scale Version 2 (EK) on average every 6 months. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: N. Burnett, D. Ridout, V. Crook, S. Robb, A. Zambon, R. Quinlivan, M. Main, A. Manzur, F. Muntoni, A. Sarkozy Source Type: research
P149 Delayed pulmonary progression in Golodirsen-treated patients with Duchenne muscular dystrophy vs mutation-matched external controls
Pulmonary decline in Duchenne muscular dystrophy (DMD) increases the risk of hospitalization, morbidity, and mortality. Golodirsen is FDA approved for the treatment of DMD in boys with mutations amenable to exon 53 and has been shown in Study 4053-101 (NCT02310906) to have functional benefits in a declining population of patients with DMD vs mutation-matched external controls (EC). This post hoc analysis compared longitudinal trajectories of percent predicted forced vital capacity (FVC%p) and projected time to cough-assist and nighttime ventilation in patients with DMD receiving golodirsen vs mutation-matched EC. (Source: ...
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: J. Iff, E. Tuttle, Y. Liu, F. Wei, N. Done, L. Servais, A. Seferian, V. Straub, M. Guglieri, E. Mercuri, F. Muntoni Source Type: research
P150 Factors affecting the measurement variability of SV95C in ambulant patients with Duchenne muscular dystrophy
Stride Velocity at the 95th Centile (SV95C) is a novel clinical outcome measure that is captured during normal daily living using wearable technology and represents the maximum ambulatory ability of a patient. SV95C is qualified by the European Medicines agency (EMA) for use as a secondary endpoint in pivotal studies in DMD, and is an important real-world functional endpoint complementary to the traditional in-clinic assessments such as the North Star Ambulatory Assessment scale and the Six Meter Walk Test. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: M. Rogers, S. Motola, D. Eggenspieler, M. Poleur, G. Parinello, D. Lozeve, A. Danon, L. Szabo, K. Aragon-Gawi ńska, A. Potulska-Chromik, N. Butoianu, C. Anghelescu, Mirea, D. Osredkar, E. Vrščaj, J. Haberlova, S. Kodsy, A. Salah, P. Strijbos, L. Serva Source Type: research
P151 Serum adipokines in Duchenne muscular dystrophy: relationships to BMI, corticosteroids, and muscle fat fraction
Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder hallmarked by muscle degeneration, replacement by fat, and weakness. Corticosteroids slow disease progression, but they also cause metabolic disruptions such as significant weight gain. For this preliminary study, we evaluated levels of serum adipokines, or factors released by adipose tissue, in a large cohort of individuals with DMD. 309 serum samples were collected from 94 participants with DMD (longitudinal samples) and 14 controls (one time point) enrolled in the ImagingDMD natural history study. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: A. Barnard, N. Ikelaar, H. Kan, E. Niks, K. Vandenborne, G. Walter, P. Spitali Source Type: research
P205 Impact of disease modifying treatment by three months of life on swallowing in spinal muscular atrophy type 1
Spinal Muscular Atrophy (SMA) Type I is a progressive neuromuscular disorder that causes rapid deterioration in an infant's ability to successfully orally feed with eventual death. Recent pharmaceutical advances have resulted in the development of disease modifying therapies (DMT) that are designed to halt neuromuscular deterioration upon administration and enable infant survival. Little is known, however, on the impacts of DMT on swallowing physiology and function. The aim of this investigation was to compare swallowing between infants who received DMT by 3 months of life and those who did not. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: K. McGrattan, A. Spoden, H. McGhee, K. Nichols, K. Hernandez, J. Ochura, R. Graham, B. Darras, A. Brown, J. Brandsema, P. Karachunski, J. Allen, A. Miles Tags: SMA – CLINICAL Source Type: research
P206 Impaired neurodevelopment in children with 5q-SMA - 2 years after newborn screening
Numerous studies have consistently found no serious adverse effects of reduced SMN protein expression on the development of cognitive function in SMA patients. However, the average intelligence quotient in SMA patients has been described as higher than average. The cognitive development of SMA patients identified by newborn screening remains largely unknown. A total of 47 SMA patients from 46 families identified through newborn screening between January 2018 and December 2020 were eligible for developmental testing using Bayley III (BSID) starting from the age of 12 months. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: H. K ölbel, M. Kopka, L. Modler, S. Plum, A. Blaschek, U. Schara-Schmidt, K. Vill, O. Schwartz, W. Müller-Felber Source Type: research
