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Introduction: The ability to individualize recommendations or expectations of disease progression based on a patient's unique characteristics has merit for use in sporadic inclusion body myositis (sIBM).Methods: Fifty-five subjects with sIBM completed a battery of strength and functional outcomes at 2 study visits. These were used to develop mathematical models of disease progression in patients with sIBM for use in clinical and research settings.Results: The 6-minute walk test (6MWT) distance declined by an average of 27.5 meters (12%) per year. Significant factors that predict 6MWT were knee extension and plantarflexion strength and body weight, whereas the ability to stand from a chair was impacted by elbow extension strength. Stepping up on a curb was influenced by the patient's age at diagnosis and by knee extension. Statistical models to predict functional decline in sIBM were developed.Conclusion: Statistical models help explain the complex factors that influence decreased walking ability and other functional activities in sIBM. Muscle Nerve 55: 526-531, 2017. [ABSTRACT FROM AUTHOR]

Introduction: Outcomes sensitive to change over time in non-ambulatory boys/men with Duchenne muscular dystrophy (DMD) are not well-established.Methods: Subjects (n = 91; 16.8 ± 4.5 years old) were assessed at baseline and 6-month intervals for 2 years. We analyzed all subjects using an intent-to-treat model and a subset of stronger subjects with Brooke Scale score ≤4, using repeated measures.Results: Eight patients (12-33 years old) died during the study. Sixty-six completed 12-month follow-up, and 51 completed 24-month follow-up. Those taking corticosteroids performed better at baseline, but rates of decline were similar. Forced vital capacity percent predicted (FVC% predicted) declined significantly only after 2 years. However, Brooke and Egen Klassifikation (EK) Scale scores, elbow flexion, and grip strength declined significantly over both 1 and 2 years.Conclusion: Brooke and EK Scale scores, elbow flexion, and grip strength were outcomes most responsive to change. FVC% predicted was responsive to change over 2 years. Corticosteroids benefited non-ambulatory DMD subjects but did not affect decline rates of measures tested here. Muscle Nerve 54: 681-689, 2016. [ABSTRACT FROM AUTHOR]

The evidence for Constraint-Induced Movement Therapy (CIMT) effectiveness for infants and toddlers with unilateral cerebral palsy is minimal. We performed a pilot study of CIMT using one-month usual care, one-month intervention, and one-month maintenance (return to usual care) phases on five infants (7- to 18-month old). For the CIMT phase, the infants received 2 hr of occupational therapy and 1 hr of parent-implemented home program for five days/week. The infants were casted for the first 23 days, and bimanual therapy was provided for the last three days. Fine motor skills for the more affected arm and gross motor skills improved significantly during the CIMT; these gains were maintained at one-month follow-up. Individual infant data show mixed effects. This pilot study provides initial evidence that CIMT is feasible for infants with unilateral cerebral palsy, and presents preliminary data for CIMT on fine and gross motor performance. [ABSTRACT FROM AUTHOR]

Objective: Dysferlinopathy is a muscular dystrophy with a highly variable clinical presentation and currently unpredictable progression. This variability and unpredictability presents difficulties for prognostication and clinical trial design. The Jain Clinical Outcomes Study of Dysferlinopathy aims to establish the validity of the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) scale and identify factors that influence the rate of disease progression using NSAD.Methods: We collected a longitudinal series of functional assessments from 187 patients with dysferlinopathy over 3 years. Rasch analysis was used to develop the NSAD, a motor performance scale suitable for ambulant and nonambulant patients. Generalized estimating equations were used to evaluate the impact of patient factors on outcome trajectories.Results: The NSAD detected significant change in clinical progression over 1 year. The steepest functional decline occurred during the first 10 years after symptom onset, with more rapid decline noted in patients who developed symptoms at a younger age (p = 0.04). The most rapidly deteriorating group over the study was patients 3 to 8 years post symptom onset at baseline.Interpretation: The NSAD is the first validated limb girdle specific scale of motor performance, suitable for use in clinical practice and clinical trials. Longitudinal analysis showed it may be possible to identify patient factors associated with greater functional decline both across the disease course and in the short-term for clinical trial preparation. Through further work and validation in this cohort, we anticipate that a disease model incorporating functional performance will allow for more accurate prognosis for patients with dysferlinopathy. ANN NEUROL 2021;89:967-978. [ABSTRACT FROM AUTHOR]

Purpose: This single-arm prospective cohort study aimed to evaluate the feasibility and utility of in-home body weight support harness system (BWSS) use in children treated for spinal muscular atrophy (SMA). Methods: Individuals with 2 or 3 copies of SMN2 who received pharmacotherapeutic treatment, had head control, and weight <50lbs were enrolled. Families were provided a BWSS and documented use. Motor outcome assessments were completed at baseline, month 3 and month 6. Families provided feedback in an end of study survey. Results: All 32 participants (2.9 (SD 1.9) yrs), improved or remained stable on all outcomes. Average reported frequency of use was 4.1(2.3) hrs/week. Controlling for other covariates, frequency of use explained over 70% of the variability in change scores. Family feedback was overwhelmingly positive. Conclusion: Use of in-home BWSS is a safe, feasible and useful option to increase exercise dosage after treatment in SMA and may help optimize motor abilities. Trial registration: Study registered with: Clinicaltrials.gov Clinicaltrials.gov identifier: NCT05715749. [ABSTRACT FROM AUTHOR]

Background: The Limb Girdle Muscular Dystrophies (LGMDs) are characterized by progressive weakness of the shoulder and hip girdle muscles as a result of over 30 different genetic mutations. This study is designed to develop clinical outcome assessments across the group of disorders. Methods/design: The primary goal of this study is to evaluate the utility of a set of outcome measures on a wide range of LGMD phenotypes and ability levels to determine if it would be possible to use similar outcomes between individuals with different phenotypes. We will perform a multi-center, 12-month study of 188 LGMD patients within the established Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Research Consortium, which is comprised of 11 sites in the United States and 2 sites in Europe. Enrolled patients will be clinically affected and have mutations in CAPN3 (LGMDR1), ANO5 (LGMDR12), DYSF (LGMDR2), DNAJB6 (LGMDD1), SGCA (LGMDR3), SGCB (LGMDR4), SGCD (LGMDR6), or SGCG (LGMDR5, or FKRP-related (LGMDR9). Discussion: To the best of our knowledge, this will be the largest consortium organized to prospectively validate clinical outcome assessments (COAs) in LGMD at its completion. These assessments will help clinical trial readiness by identifying reliable, valid, and responsive outcome measures as well as providing data driven clinical trial decision making for future clinical trials on therapeutic agents for LGMD. The results of this study will permit more efficient clinical trial design. All relevant data will be made available for investigators or companies involved in LGMD therapeutic development upon conclusion of this study as applicable. Trial registration: Clinicaltrials.gov NCT03981289; Date of registration: 6/10/2019. [ABSTRACT FROM AUTHOR]

• SMA natural history has dramatically changed with newborn screening. • Here we report long term follow up of 46 children with SMA and treated with onasemnogene abeparvovec. • Despite treatment within the first 30 days of life, ∼50 % of babies with 2 copies of SMN2 could do better. 5q spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by absence of the SMN1 gene with three FDA approved genetic therapies which significantly improve outcomes. The AAV9 mediated gene replacement therapy, onasemnogene abeparvovec, has the greatest potential for side effects. Here we report the safety and outcomes from 46 children treated with onasemnogene abeparvovec in the state of Ohio between December 2018 and January 2023. In our cohort, onasemnogene abeparvovec treatment remained safe and no child experienced any significant adverse events, including thrombotic microangiopathy, liver failure or death. All children experienced benefit, although the benefit in those with 2 copies of SMN2 was variable. 79 % of the children treated when symptomatic had a SMN2 modifying therapy added on. With careful screening and post treatment monitoring, onasemnogene abeparvovec is safe and effective for children with SMA in the state of Ohio, but more work needs to be done to ensure optimal outcomes for all children with 2 copies of SMN2. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Delandistrogene moxeparvovec is indicated in the United States for the treatment of ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene. Long‐term delandistrogene moxeparvovec microdystrophin protein (a shortened dystrophin that retains key functional domains of the wild‐type protein) expression may positively alter disease progression in patients with DMD. We evaluated long‐term safety and functional outcomes of delandistrogene moxeparvovec in patients with DMD. Methods: An open‐label, phase 1/2a, nonrandomized controlled trial (Study 101; NCT03375164) enrolled ambulatory males, ≥4 to <8 years old, with DMD. Patients received a single intravenous infusion (2.0 × 1014 vg/kg by supercoiled quantitative polymerase chain reaction) of delandistrogene moxeparvovec and prednisone (1 mg/kg/day) 1 day before to 30 days after treatment. The primary endpoint was safety. Functional outcomes were change from baseline in North Star Ambulatory Assessment (NSAA) and timed function tests. Results: Four patients (mean age, 5.1 years) were enrolled. There were 18 treatment‐related adverse events; all occurred within 70 days posttreatment and resolved. Mean NSAA total score increased from 20.5 to 27.5, baseline to year 4, with a mean (standard deviation) change of +7.0 (2.9). Post hoc analysis demonstrated a statistically significant and clinically meaningful 9‐point difference in NSAA score, relative to a propensity‐score–weighted external control cohort (least‐squares mean [standard error] = 9.4 [3.4]; P =.0125). Discussion: Gene transfer therapy with delandistrogene moxeparvovec treatment is well tolerated, with a favorable safety profile. Functional improvements are sustained through 4 years, suggesting delandistrogene moxeparvovec may positively alter disease progression. See Editorial on pages 4–6 in this issue. [ABSTRACT FROM AUTHOR]

Objective: We created WiTNNess as a hybrid prospective/cross‐sectional observational study to simulate a clinical trial for infantile‐onset TNNT1 myopathy. Our aims were to identify populations for future trial enrollment, rehearse outcome assessments, specify endpoints, and refine trial logistics. Methods: Eligible participants had biallelic pathogenic variants of TNNT1 and infantile‐onset proximal weakness without confounding conditions. The primary endpoint was ventilator‐free survival. "Thriving" was a secondary endpoint defined as the ability to swallow and grow normally without non‐oral feeding support. Endpoints of gross motor function included independent sitting and standing as defined by the Word Health Organization, a novel TNNT1 abbreviated motor score, and video mapping of limb movement. We recorded adverse events, concomitant medications, and indices of organ function to serve as comparators of safety in future trials. Results: Sixteen children were enrolled in the aggregate cohort (6 prospective, 10 cross‐sectional; median census age 2.3 years, range 0.5–13.8). Median ventilator‐free survival was 20.2 months and probability of death or permanent mechanical ventilation was 100% by age 60 months. All six children (100%) in the prospective arm failed to thrive by age 12 months. Only 2 of 16 (13%) children in the aggregate cohort sat independently and none stood alone. Novel exploratory motor assessments also proved informative. Laboratory and imaging data suggest that primary manifestations of TNNT1 deficiency are restricted to skeletal muscle. Interpretation: WiTNNess allowed us to streamline and economize the collection of historical control data without compromising scientific rigor, and thereby establish a sound operational framework for future clinical trials. [ABSTRACT FROM AUTHOR]

Background and Purpose: Patients with Duchenne muscular dystrophy (DMD) change their movement patterns to compensate for muscle weakness. The Duchenne Video Assessment (DVA) measures ease of movement through evaluation of compensatory movements. The DVA directs caregivers to video record patients performing home‐based movement tasks using a mobile application, and DVA‐certified physical therapists evaluate the videos using scorecards with prespecified compensatory movement criteria. Two qualitative interview studies were conducted to select movement tasks for the DVA that are relevant to patients with DMD and able to reflect changes in function. Methods: Qualitative interviews with eligible physical therapists were conducted remotely. Physical therapists were asked to spontaneously suggest movement tasks prior to evaluating specific movement tasks selected a priori. Analysts conducted a content analysis to investigate whether movement tasks selected a priori were confirmed as relevant to the population of interest and able to show changes in function. Results: The studies included five physical therapists to select tasks for ambulatory patients with DMD and six for non‐ambulatory patients. For an ambulatory population, all five experts confirmed Climb Five Stairs, Run, Stand Up from Sitting, Sit Up from Supine, and Jump Forward, and four (80%) confirmed Walk as relevant and able to show functional changes. For a non‐ambulatory population, all six experts confirmed Eat 10 Bites, Roll Over in Bed, Shift Weight in Bed, Take T‐Shirt Off, Put T‐Shirt On, Put Arms on Armrest, and Reach Across Table to Grab Cell Phone, and five (83%) confirmed Raise Hands Above Head as relevant and able to show functional changes. Discussion: Physical therapists confirmed the DVA movement tasks as relevant to patients with DMD and able to reflect changes in function. The use of the DVA in clinical trials provides an opportunity to collect data not seen in clinic and reduce travel burden for families. [ABSTRACT FROM AUTHOR]

An abstract of the study "Delivery of Constraint-Induced Movement Therapy Through a Video Game for Individuals with Hemiparesis Post-Stroke," by Jana Jaffe, Linda Lowes, Alexandra Borstad, Lise Worthen-Chaudhari, Roger Crawfis, David Maung, Amelia Siles and Lynne Gauthier is presented.

Background: Patient-centered research has emerged as critically important for understanding the impact of treatments on key stakeholders. The subjective experience of quality of life (QOL) is increasingly recognized as fundamental to delineating treatment goals. The present study utilized content analysis of qualitative data and quantitative analysis to highlight important domains of disease burden and underlying reasons for their importance, and to characterize goals for new treatments for Duchenne Muscular Dystrophy (DMD). Results: The study sample reflected the perspectives of DMD patients and caregivers representing ambulatory, transitional, and non-ambulatory stages of disability progression (n = 20 per category). Open-ended interviews were content-analyzed and non-parametric statistical tests were used to compare ambulation groups. As patients progressed in disability, the noted DMD burdens reflected some differences in functional areas. While daily functioning and sports/recreation remained the most important priority areas across ambulation groups, "health" became less prominent as the disability progressed from ambulatory to transitional to non-ambulatory phases of disability; whereas relationships became more prominent as one progressed to the non-ambulatory phase from the ambulatory or transitional phases (Kruskall Wallis H = 12.24 and 5.28, p = 0.002 and 0.02, respectively). When asked why their burdens were important to them and how it impacted their or their child's life, self-esteem/confidence was most important for ambulatory patients, and became less prominent for patients in the transitional and non-ambulatory phases of disability (Kruskall Wallis H = 9.46, p = 0.009). In contrast, independence was less important for ambulatory patients, and became increasing prominent for patients in the transitional and non-ambulatory phases of disability (Kruskall Wallis H = 7.35, p = 0.025). Emotional functioning was most prominent for all ambulation groups on their best and worst days. Goals for new DMD treatments focused on functional goals, general QOL goals, and concerns about safety, ease of use, and effectiveness. Conclusion: This study provides useful information about treatment goals for DMD from the perspective of patients and their caregivers. It highlights some consistent values across the disability trajectory, as well as introducing an evolution of priorities as the person with DMD becomes more disabled. Results provide a roadmap for patient-centered DMD drug development. [ABSTRACT FROM AUTHOR]

• Remote outcomes may reduce travel burden and access to quality care and research. • Remote testing strategies were implemented in response to the pandemic. • Validation of remote methodologies are needed prior to broad implementation. • Remote testing and alternative monitoring strategies are currently being investigated. [ABSTRACT FROM AUTHOR]

Objective The North Star Assessment for limb-girdle type muscular dystrophies (NSAD), a clinician-reported outcome measure (ClinRO) of motor performance, was initially developed and validated for use in dysferlinopathy, an autosomal recessive form of limb-girdle muscular dystrophy (LGMD R2/2B). Recent developments in treatments for limb-girdle muscular dystrophies (LGMD) have highlighted the urgent need for disease-specific ClinROs. The purpose of this study was to understand the ability of the NSAD to quantify motor function across the broad spectrum of LGMD phenotypes. Methods Assessments of 130 individuals with LGMD evaluated by the physical therapy teams at Nationwide Children's Hospital and the John Walton Muscular Dystrophy Research Centre were included in the analysis. NSAD, 100-m timed test (100MTT), and Performance of Upper Limb 2.0 assessment data were collected. Psychometric analysis with Rasch measurement methods was used to examine the NSAD for suitability and robustness by determining the extent to which the observed data "fit" with predictions of those ratings from the Rasch model. The NSAD score was correlated with the 100MTT and Performance of Upper Limb 2.0 assessment scores for external construct validity. Results The NSAD demonstrated a good spread of items covering a continuum of abilities across both individuals who had LGMD and were ambulatory and individuals who had LGMD and were weaker and nonambulatory. Items fit well with the construct measured, validating a summed total score. The NSAD had excellent interrater reliability [intraclass correlation coefficient (ICC) = 0.986, 95% CI = 0.981–0.991] and was highly correlated with the 100MTT walk/run velocity (Spearman rho correlation coefficient of rs(134) = .92). Conclusion Although LGMD subtypes may differ in age of onset, rate of progression, and patterns of muscle weakness, the overall impact of progressive muscle weakness on motor function is similar. The NSAD is a reliable and valid ClinRO of motor performance for individuals with LGMD and is suitable for use in clinical practice and research settings. Impact Recent developments in potential pharmacological treatments for LGMD have highlighted the urgent need for disease-specific outcome measures. Validated and meaningful outcome measures are necessary to capture disease presentation, to inform expected rates of progression, and as endpoints for measuring the response to interventions in clinical trials. The NSAD, a scale of motor performance for both individuals who have LGMD and are ambulatory and those who are nonambulatory, is suitable for use in clinical and research settings. [ABSTRACT FROM AUTHOR]

Objective: To continue evaluation of the long-term efficacy and safety of eteplirsen, a phosphorodiamidate morpholino oligomer designed to skip DMD exon 51 in patients with Duchenne muscular dystrophy (DMD). Three-year progression of eteplirsen-treated patients was compared to matched historical controls (HC).Methods: Ambulatory DMD patients who were ≥7 years old and amenable to exon 51 skipping were randomized to eteplirsen (30/50mg/kg) or placebo for 24 weeks. Thereafter, all received eteplirsen on an open-label basis. The primary functional assessment in this study was the 6-Minute Walk Test (6MWT). Respiratory muscle function was assessed by pulmonary function testing (PFT). Longitudinal natural history data were used for comparative analysis of 6MWT performance at baseline and months 12, 24, and 36. Patients were matched to the eteplirsen group based on age, corticosteroid use, and genotype.Results: At 36 months, eteplirsen-treated patients (n = 12) demonstrated a statistically significant advantage of 151m (p < 0.01) on 6MWT and experienced a lower incidence of loss of ambulation in comparison to matched HC (n = 13) amenable to exon 51 skipping. PFT results remained relatively stable in eteplirsen-treated patients. Eteplirsen was well tolerated. Analysis of HC confirmed the previously observed change in disease trajectory at age 7 years, and more severe progression was observed in patients with mutations amenable to exon skipping than in those not amenable. The subset of patients amenable to exon 51 skipping showed a more severe disease course than those amenable to any exon skipping.Interpretation: Over 3 years of follow-up, eteplirsen-treated patients showed a slower rate of decline in ambulation assessed by 6MWT compared to untreated matched HC. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Dysferlinopathy demonstrates heterogeneity in muscle weakness between patients, which can progress at different rates over time. Changing muscle strength due to disease progression or from an investigational product is associated with changing functional ability. The purpose of this study was to compare three methods of strength testing used in the Clinical Outcome Study (COS) for dysferlinopathy to understand which method and which muscle groups were most sensitive to change over time. Methods: Patients were evaluated at each study visit using functional scales, manual muscle testing, and handheld dynamometry (HHD) at all 15 sites. A fixed‐frame system (Fixed) was used at a subset of seven sites. Screening and baseline visits were evaluated for reliability. Data over a 1‐year period were analyzed to determine sensitivity to change among strength modalities and individual muscle groups. Results: HHD and Fixed captured significant change across 1 year in summed muscle strength score of four muscle groups (P <.01). Strength summed scores were significantly correlated with functional scales (rho = 0.68‐0.92, P <.001). Individual muscle groups, however, showed high levels of variability between visits. Discussion: Although both HHD and Fixed demonstrate change over 12 months, HHD is a less expensive option that provides data on a continuous scale and may be easier to implement. Due to variability in strength measures, researchers should carefully consider use of strength testing as an outcome and may wish to select functional measures with less variability as clinical trial endpoints. [ABSTRACT FROM AUTHOR]

• The most prevalent themes were related to mobility and ambulation. • Patients reported a high frequency of social limitations and emotional challenges. • LGMD subtypes share a similar profile of symptoms despite different gene mutations. • Unemployed patients perceived a greater impact of several themes on quality of life. • This patient-reported approach highlights symptoms that matter the most. This study determined the frequency and impact of symptoms on quality of life in patients diagnosed with limb girdle muscular dystrophy (LGMD). Participants with a diagnosis of LGMD in registries based at the Coalition to Cure Calpain-3, the Jain foundation, and the Global FKRP Registry competed a survey to report the frequency and relative impact of themes and symptoms of LGMD. Frequency, mean impact, and population impact scores were calculated, and responses were categorized by age, symptom duration, gender, employment status, use of assistive devices, and LGMD subtypes. 134 participants completed the survey. The most prevalent themes included an inability to do activities (100%), limitation with mobility (99.3%), and lower extremity weakness (97.0%). Themes with the greatest impact were: limitations with mobility, lower extremity weakness, and an inability to do activities. Symptom duration and the use of assistive devices were associated with the presence of multiple themes. Employment was associated with the impact of several themes with no differences in frequency. The prevalence and impact of these themes vary in the LMGD population. The most prevalent and impactful themes were related to weakness, but additional concerns related to emotional challenges should also be considered in clinical and research settings. [ABSTRACT FROM AUTHOR]

Background: Approved treatments in spinal muscular atrophy (SMA) have resulted in unprecedented gains for many individuals. Use of available outcomes, typically developed for a specific type of SMA, do not cover the range of progression, often resulting in a battery of functional testing being completed at visits. Our objective was to validate the Neuromuscular Gross Motor Outcome (GRO) as a tool to quantify function in SMA across the span of abilities.Methods: Patients with genetically confirmed SMA completed functional testing at each visit including the Neuromuscular GRO and other appropriate gross motor outcomes.Results: We enrolled 91 patients with SMA types 1 to 3 between 8 days and 32.1 years. The GRO utilizes a 0- to 2-point scale with scores in our cohort ranging from 1 to 95 points with no floor or ceiling effect. GRO scores were significantly different across functional categories (P < 0.001) and treatment status (P = 0.01) and correlated to other functional assessments (P ≤ 0.001). All patients were measured using the GRO, whereas traditional outcomes were only appropriate on 36% to 59% of our cohort.Conclusion: The Neuromuscular GRO quantifies function across the span of age and abilities included in our cohort, allowing for continuous longitudinal monitoring on one scale to reduce the burden of testing in our heterogeneous clinic population. [ABSTRACT FROM AUTHOR]

Introduction: Clinical trials targeting younger cohorts of boys with Duchenne muscular dystrophy are necessary as earlier intervention may maximize treatment effect. Boys with Duchenne muscular dystrophy often have gross motor delays very early in life, and although they gain skills, they are on a lower trajectory than typical peers. Quantifying the natural rate of motor maturation in Duchenne muscular dystrophy from an early age permits identification of deviations from the expected trajectory related to treatment effects.Methods: The purpose of our study was to define the natural history in boys aged from ≥3 to <8 years using the North Star Ambulatory Assessment (NSAA), 100-meter timed test (100m), 10-meter walk/run (10m), time to rise (Rise), and 4-stair climb (4SC). Assessments were completed as standard of care during regularly scheduled clinic visits.Results: One hundred sixty-two boys with DMD aged 3.1 to 7.9 years on glucocorticoids were evaluated using one or more of the following tests as appropriate for age: NSAA (N = 158; 3.1-7.9 years), 100m (N = 131; 3.4-7.9 years), 10m (N = 162; 3.1-7.9 years), Rise (N = 160; 3.1-7.9 years), and 4SC (N = 153; 3.1-7.9 years). Longitudinal data are presented by age in a subcohort (N = 64).Conclusions: Our study documents the baseline function of boys with DMD who are being treated with corticosteroids. These data will be useful to compare ongoing and future therapeutic intervention(s) for DMD. [ABSTRACT FROM AUTHOR]

Timed walking tests are often used to measure function in boys with Duchenne muscular dystrophy (DMD). Our objective was to evaluate the 100 meter timed test (100m), a fixed distance test of maximal performance, for use in DMD. To this end, we sought to establish normative 100m performance in healthy controls, compare DMD performance to controls, and evaluate the reliability of 100m. Seventy-two boys with DMD (18 steroid-naïve, 54 on steroids) and 599 controls (4–14 years) completed the 100m as speedily as possible on a 25-meter track. Repeat testing was completed between 1 and 42 days later and again at 1 year in a subgroup of 96 control boys. Additionally 35 DMD boys were followed longitudinally (5–19 months). Descriptive statistics are presented by age and cohort. There was a significant difference in performance between groups (p < 0.01). Age and body mass index (BMI) significantly influenced 100m (p < 0.0001) in the control cohort. Test–retest reliability was excellent for both cohorts (ICC > 0.90, p < 0.001). Normative data can be used to determine percent-predicted 100m times to quantify the severity of running impairment in children with a motor deficit. Performance of 100m follows the natural history established by other outcome measures in DMD. [ABSTRACT FROM AUTHOR]

Therapeutic trials in Duchenne Muscular Dystrophy (DMD) exclude young boys because traditional outcome measures rely on cooperation. The Bayley III Scales of Infant and Toddler Development (Bayley III) have been validated in developing children and those with developmental disorders but have not been studied in DMD. Expanded Hammersmith Functional Motor Scale (HFMSE) and North Star Ambulatory Assessment (NSAA) may also be useful in this young DMD population. Clinical evaluators from the MDA-DMD Clinical Research Network were trained in these assessment tools. Infants and boys with DMD (n =24; 1.9±0.7years) were assessed. The mean Bayley III motor composite score was low (82.8±8; p ⩽.0001) (normal=100±15). Mean gross motor and fine motor function scaled scores were low (both p ⩽.0001). The mean cognitive comprehensive (p =.0002), receptive language (p ⩽.0001), and expressive language (p =.0001) were also low compared to normal children. Age was negatively associated with Bayley III gross motor (r =−0.44; p =.02) but not with fine motor, cognitive, or language scores. HFMSE (n =23) showed a mean score of 31±13. NSAA (n =18 boys; 2.2±0.4years) showed a mean score of 12±5. Outcome assessments of young boys with DMD are feasible and in this multicenter study were best demonstrated using the Bayley III. [ABSTRACT FROM AUTHOR]

Purpose: Traditional value assessment frameworks are challenged in comprehensively assessing the societal value new therapies bring to individuals with rare, progressive, genetic, fatal, neuromuscular diseases such as Duchenne muscular dystrophy (DMD). The objective of this study was to identify how value assessment frameworks may need to be adapted to measure the value to society of DMD therapies., Patients and Methods: Three stakeholder groups (6 patient advocates, 4 clinicians, 3 health economists; N = 13) participated in semi-structured interviews around the International Society for Pharmacoeconomics and Outcomes Research's Value Flower, which includes elements to consider within value assessments of healthcare technologies., Results: All stakeholders agreed that traditional value assessment frameworks based on the quality-adjusted life year (QALY) are narrow and will undervalue new DMD therapies. All stakeholders expressed some level of concern that using the QALY as a key metric of value discriminates against patients with severe progressive diseases and disabilities. Some stakeholders saw value in using the QALY for cross-disease comparisons in resource-constrained environments if the methodology was appropriate. All stakeholders recommended considering additional elements of value in decision-making around new DMD therapies. These elements reflect: economic and humanistic costs incurred by patients, caregivers, and families with Duchenne, such as indirect out-of-pocket costs, lost productivity, and family spillovers; meaningful attributes for individuals with disabilities and high unmet need, such as severity of disease, value of hope, and real option value; and factors that contribute to improvements in population health, such as insurance value, equity, and scientific spillovers., Conclusion: These findings highlight the need to expand traditional value assessment frameworks and take a holistic approach that incorporates the perspectives of individuals with Duchenne, caregivers, clinicians, and health economists when assessing the societal value of new DMD therapies. Broadening value assessment will prevent restricted or delayed access to therapies for individuals with Duchenne., Competing Interests: RF, PF, AK, and DM have no conflicts of interest to report for this work. KM reports grants from Sarepta, outside the submitted work. MP reports grants from Sarepta Therapeutics, PTC Therapeutics, Pfizer, Edgewise Therapeutics, and NS Pharma, outside the submitted work. CGL serves on advisory boards/consults with Avidity, Biogen, Roche, Novartis, and Sarepta Therapeutics. LL provides training for Sarepta Therapeutics and reports personal fees from Sarepta Therapeutics and Atom International for training services. NLK serves on advisory boards/consults with Astellas, Argenx, Biogen, Novartis, Roche, and Sarepta Therapeutics. PBS has served as a consultant to Novartis Gene Therapies, Biogen, Genentech, Sarepta Therapeutics, Pfizer, Solid Biosciences, Astellas Gene Therapies, Argenx, Alexion, Catalyst Pharma, Grifols, Avidity, Dyne, AMO Pharma, Abcuro, UCB, and CSL Behring. JK is an employee of SNELL Medical Communication, Inc., which has received funding from Sarepta Therapeutics. PJN has consulted and participated on advisory boards for Sarepta Therapeutics and reports personal fees from Roche Holding AG. JS is an employee of FTI Consulting, a consulting firm to healthcare, life sciences, and other industries. RJW served as a consultant to Sarepta Therapeutics in the work leading to the creation of this manuscript and has served on advisory boards and as a consultant on projects sponsored by several other biopharmaceutical companies. RJW also reports personal fees from Sarepta Therapeutics. The authors report no other conflicts of interest in this work., (© 2024 Fischer et al.)

Dysferlin-deficient limb girdle muscular dystrophy (LGMD R2), also referred to as dysferlinopathy, can be associated with respiratory muscle weakness as the disease progresses. Clinical practice guidelines recommend biennial lung function assessments in patients with dysferlinopathy to screen for respiratory impairment. However, lack of universal access to spirometry equipment and trained specialists makes regular monitoring challenging. This study investigated the use of the Performance of Upper Limb (PUL) clinical scale entry item as a low-cost screening tool to identify patients with dysferlinopathy at risk of respiratory impairment. Using data from 193 patients from the Jain Foundation's International Clinical Outcomes Study, modelling identified a significant positive relationship between the PUL entry item and forced vital capacity (FVC). Eighty-eight percent of patients with the lowest PUL entry item score of 1 presented with FVC % predicted values of <60 %, suggestive of respiratory impairment. By contrast, only 10 % of the remainder of the cohort (PUL entry item of 2 or more) had an FVC of <60 %. This relationship also held true when accounting for ambulatory status, age, and sex as possible confounding factors. In summary, our results suggest that the PUL entry item could be implemented in clinical practice to screen for respiratory impairment where spirometry is not readily available., Competing Interests: Declaration of competing interest Apart from the grant from the Jain Foundation that financed the study, there are no relevant conflicts of interest that impact on the paper referenced above., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Conducting functional assessments remotely can help alleviate the burden of in-person assessment on patients with Duchenne muscular dystrophy and their caregivers. The objective of this study was to evaluate whether scores from remote functional assessment of patients with Duchenne muscular dystrophy correspond to in-person scores on the same functional assessments. Remote live stream versus in-person scores on the North Star Ambulatory Assessment (including time [seconds] to complete the 10-meter walk/run and time to rise from the floor [supine to stand]) were assessed using statistical analyses, including intraclass correlation coefficient, and Pearson, Spearman, and Bland-Altman analyses. The remote and in-clinic assessments had to occur within 2 weeks of one another to be considered for this analysis. This analysis included patients with Duchenne muscular dystrophy, aged 4 to 7 years. Participants in this analysis received delandistrogene moxeparvovec (as part of SRP-9001-101 [Study 101; NCT03375164] or SRP-9001-102 [Study 102; NCT03769116]) or were randomized to receive placebo (in Part 1 of Study 102). This study evaluates score reproducibility between live stream remote scoring versus in-person functional assessments as determined by intraclass correlation coefficient, and Pearson, Spearman, and Bland-Altman analyses. The results showed that scores from remote functional assessment of patients with Duchenne muscular dystrophy strongly correlated with those obtained in person. These findings demonstrate congruence between live stream remote and in-person functional assessment and suggest that remote assessment has the potential to reduce the burden on a family by supplementing in-clinic visits., Competing Interests: The authors of this paper have read the journal’s policy and have the following competing interests: Linda P Lowes reports receiving salary support from Sarepta Therapeutics, Inc. through Nationwide Children’s Hospital to subsidize training and quality control activities for ongoing clinical trials and licensing fees for natural history data. Lindsay N Alfano reports receiving salary support from Sarepta Therapeutics, Inc. through Nationwide Children’s Hospital to subsidize training and quality control activities for their ongoing clinical trials. Megan A Iammarino reports no conflicts of interest. Natalie F Reash reports receiving salary support from Sarepta Therapeutics, Inc. for Clinical Evaluator training for ongoing and upcoming clinical trials. Kathryn Giblin is an employee of Eli Lilly and was previously an employee of Sarepta Therapeutics, Inc. and may have stock options. Lixi Yu, Shufang Wang, and Rachel Salazar are employees of Sarepta Therapeutics, Inc. and may have stock options. Larry Hu was an employee of Sarepta during the execution of this work. Jerry R Mendell received study funding from Sarepta Therapeutics while at Nationwide Children’s Hospital at the time of the study, and is currently an employee of Sarepta Therapeutics. Jerry R Mendell is a co-inventor of AAVrh74.MHCK7.micro-dys technology. The authors confirm that this does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 P. Lowes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Muscular dystrophies (MD) are a group of genetic neuromuscular disorders that cause progressive weakness and loss of muscles over time, influencing 1 in 3500-5000 children worldwide. New and exciting treatment options have led to a critical need for a clinical post-marketing surveillance tool to confirm the efficacy and safety of these treatments after individuals receive them in a commercial setting. For MDs, functional gait assessment is a common approach to evaluate the efficacy of the treatments because muscle weakness is reflected in individuals' walking patterns. However, there is little incentive for the family to continue to travel for such assessments due to the lack of access to specialty centers. While various existing sensing devices, such as cameras, force plates, and wearables can assess gait at home, they are limited by privacy concerns, area of coverage, and discomfort in carrying devices, which is not practical for long-term, continuous monitoring in daily settings. In this study, we introduce a novel functional gait assessment system using ambient floor vibrations, which is non-invasive and scalable, requiring only low-cost and sparsely deployed geophone sensors attached to the floor surface, suitable for in-home usage. Our system captures floor vibrations generated by footsteps from patients while they walk around and analyzes such vibrations to extract essential gait health information. To enhance interpretability and reliability under various sensing scenarios, we translate the signal patterns of floor vibration to pathological gait patterns related to MD, and develop a hierarchical learning algorithm that aggregates insights from individual footsteps to estimate a person's overall gait performance. When evaluated through real-world experiments with 36 subjects (including 15 patients with MD), our floor vibration sensing system achieves a 94.8% accuracy in predicting functional gait stages for patients with MD. Our approach enables accurate, accessible, and scalable functional gait assessment, bringing MD progressive tracking into real life., (© 2024. The Author(s).)

Limb-girdle muscular dystrophy 2E/R4 is caused by mutations in the β-sarcoglycan (SGCB) gene, leading to SGCB deficiency and consequent muscle loss. We developed a gene therapy approach based on functional replacement of the deficient SCB protein. Here we report interim results from a first-in-human, open-label, nonrandomized, phase 1/2 trial evaluating the safety and efficacy of bidridistrogene xeboparvovec, an adeno-associated virus-based gene therapy containing a codon-optimized, full-length human SGCB transgene. Patients aged 4-15 years with confirmed SGCB mutations at both alleles received one intravenous infusion of either 1.85 × 10 13 vector genome copies kg - 1 (Cohort 1, n = 3) or 7.41 × 10 13 vector gene copies kg -1 (Cohort 2, n = 3). Primary endpoint was safety, and secondary endpoint was change in SGCB expression in skeletal muscle from baseline to Day 60. We report interim Year 2 results (trial ongoing). The most frequent treatment-related adverse events were vomiting (four of six patients) and gamma-glutamyl transferase increase (three of six patients). Serious adverse events resolved with standard therapies. Robust SGCB expression was observed: Day 60 mean (s.d.) percentage of normal expression 36.2% (2.7%) in Cohort 1 and 62.1% (8.7%) in Cohort 2. Post hoc exploratory analysis showed preliminary motor improvements using the North Star Assessment for Limb-girdle Type Muscular Dystrophies maintained through Year 2. The 2-year safety and efficacy of bidridistrogene xeboparvovec support clinical development advancement. Further studies are necessary to confirm the long-term safety and efficacy of this gene therapy. ClinicalTrials.gov registration: NCT03652259 ., (© 2024. The Author(s).)

Single exon duplications account for disease in a minority of Duchenne muscular dystrophy patients. Exon skipping in these patients has the potential to be highly therapeutic through restoration of full-length dystrophin expression. We conducted a 48-week open label study of casimersen and golodirsen in 3 subjects with an exon 45 or 53 duplication. Two subjects (aged 18 and 23 years) were non-ambulatory at baseline. Upper limb, pulmonary, and cardiac function appeared stable in the 2 subjects in whom they could be evaluated. Dystrophin expression increased from 0.94 % ±0.59% (mean±SD) of normal to 5.1% ±2.9% by western blot. Percent dystrophin positive fibers also rose from 14% ±17% at baseline to 50% ±42% . Our results provide initial evidence that the use of exon-skipping drugs may increase dystrophin levels in patients with single-exon duplications.

Background: Duchenne muscular dystrophy (DMD) is a rare, severe, fatal neuromuscular disease characterized by progressive atrophy and muscle weakness, resulting in loss of ambulation, decreased upper body function, and impaired cardiorespiratory function. This study aimed to generate qualitative evidence to describe the primary symptoms and impacts of DMD in ambulatory and non-ambulatory patients as reported by patient/caregiver dyads. Information was also gathered on expectations for future DMD treatments., Methods: Forty-six dyads (caregiver and patients with DMD aged 4 to 22 years) participated in 60-min semi-structured video interviews. Interview transcripts were analyzed using thematic analysis. Differences in experiences with DMD by ambulation status were examined., Results: Mean ages of ambulatory (n = 28) and non-ambulatory participants (n = 18) were 8.7 and 11.3 years, respectively, with an average age of diagnosis of 3.7 years (SD = 2.3). The primary symptoms reported by both groups were lack of strength (ambulatory: n = 28, 100.0%; non-ambulatory: n = 17, 94.4%) and fatigue (ambulatory: n = 24, 85.7%; non-ambulatory: n = 14, 77.8%). Physical function was the domain that was most impacted by DMD, with participants describing progressive decline of physical function due to loss of physical strength as the primary defining feature of the disease across all stages of ambulatory ability. For those who maintained ambulatory ability at the time of the interview, physical function impacts described impaired mobility (e.g., climbing stairs: n = 16, 57.1%; running: n = 13, 46.4%), impaired upper body function, in particular fine motor skills like holding a pen/pencil or buttoning clothes (n = 17, 60.7%), problem with transfers (e.g., getting off the floor: n = 10, 35.7%), and activities of daily living (ADLs; n = 15, 53.6%). For non-ambulatory participants, the functional impacts most frequently described were problems with transfers (e.g., getting in/out of bed: n = 13, 72.2%; getting in/out of chair or position in bed: both n = 10, 55.6%), impaired upper body function (reaching: n = 14, 77.8%), and ADLs (n = 15, 83.3%). Meaningful treatment goals differed by ambulatory status; for ambulatory participants, goals included maintaining current functioning (n = 20, 71.4%), improving muscle strength (n = 7, 25.9%), and reducing fatigue (n = 6, 22.2%). For non-ambulatory participants, these included increased upper body strength (n = 8, 42.1%) and greater independence in ADLs (n = 6, 31.6%). A preliminary conceptual model was developed to illustrate the primary symptoms and physical function impacts of DMD and capture their relationship to disease progression., Conclusion: This study contributes to the limited qualitative literature by characterizing impacts of physical limitations and symptoms of DMD on disease progression and thus providing insights into the lived experience with DMD. Differences in treatment goals were also identified based on ambulatory status. Taken together, these findings can help inform patient-centered measurement strategies for evaluating outcomes in DMD clinical research., (© 2023. The Author(s).)

Introduction: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene transfer therapy designed for targeted expression of SRP-9001 dystrophin protein, a shortened dystrophin retaining key functional domains of the wild-type protein. Methods: This Phase 2, double-blind, two-part (48 weeks per part) crossover study (SRP-9001-102 [Study 102]; NCT03769116) evaluated delandistrogene moxeparvovec in patients, aged ≥4 to <8 years with Duchenne muscular dystrophy. Primary endpoints (Part 1) were change from baseline (CFBL) in SRP-9001 dystrophin expression (Week 12), by Western blot, and in North Star Ambulatory Assessment (NSAA) score (Week 48). Safety assessments included treatment-related adverse events (TRAEs). Patients were randomized and stratified by age to placebo (n = 21) or delandistrogene moxeparvovec (n = 20) and crossed over for Part 2. Results: SRP-9001 dystrophin expression was achieved in all patients: mean CFBL to Week 12 was 23.82% and 39.64% normal in Parts 1 and 2, respectively. In Part 1, CFBL to Week 48 in NSAA score (least-squares mean, LSM [standard error]) was +1.7 (0.6) with treatment versus +0.9 (0.6) for placebo; p = 0.37. Disparity in baseline motor function between groups likely confounded these results. In 4- to 5-year-olds with matched baseline motor function, CFBL to Week 48 in NSAA scores was significantly different (+2.5 points; p = 0.0172), but not significantly different in 6-to-7-year-olds with imbalanced baseline motor function (-0.7 points; p = 0.5384). For patients treated with delandistrogene moxeparvovec in Part 2, CFBL to Week 48 in NSAA score was +1.3 (2.7), whereas for those treated in Part 1, NSAA scores were maintained. As all patients in Part 2 were exposed to treatment, results were compared with a propensity-score-weighted external control (EC) cohort. The LSM difference in NSAA score between the Part 2 treated group and EC cohort was statistically significant (+2.0 points; p = 0.0009). The most common TRAEs were vomiting, decreased appetite, and nausea. Most occurred within the first 90 days and all resolved. Discussion: Results indicate robust expression of SRP-9001 dystrophin and overall stabilization in NSAA up to 2 years post-treatment. Differences in NSAA between groups in Part 1 were not significant for the overall population, likely because cohorts were stratified only by age, and other critical prognostic factors were not well matched at baseline., Competing Interests: DG, SL, SW, RP, TS, LRR-K are empolyed by Sarepta Therapeutics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mendell, Shieh, McDonald, Sahenk, Lehman, Lowes, Reash, Iammarino, Alfano, Sabo, Woods, Skura, Mao, Staudt, Griffin, Lewis, Wang, Potter, Singh and Rodino-Klapac.)

The purpose of this study was to quantitate motor performance in 196 genetically confirmed steroid-naïve boys with Duchenne muscular dystrophy (DMD), to evaluate the test-retest reliability of measures of motor performance in young DMD boys, and to assess correlations among the different functional outcomes including timed tests. Boys aged 4-7 years were recruited in the FOR-DMD study, a comparative effectiveness study of different steroid regimens in DMD. Eligible boys had to be able to rise from the floor independently and to perform pulmonary function testing consistently. The boys were evaluated with standardized assessments at the screening and baseline visits at 32 sites in 5 countries (US, UK, Canada, Italy, Germany). Assessments included timed rise from floor, timed 10 m walk/run, six-minute walk distance, North Star Ambulatory Assessment (NSAA) and forced vital capacity (FVC). Mean age at baseline was 5.9 years (range 4.1-8.1 years). Test-retest reliability was high for functional assessments, regardless of time lag between assessments (up to 90 days) and for the majority of age groups. Correlations were strong among the functional measures and timed tests, less so with FVC. Physiotherapy measures are reliable in a young, steroid-naïve population and rise from floor velocity appears to be a sensitive measure of strength in this population., Competing Interests: Declaration of Competing Interests Anna G. Mayhew has participated in SAB meetings for Roche, Regenxbio, Summit, PTC and Biogen and performs Consultancy work (training physiotherapists for trial in DMD) for Roche, Pfizer, PTC, Summit, Sarepta, Lysogene, Italfarmaco, Amicus, Biogen and Avexis. Dionne Moat provides consultancy services for the following companies: ATOM International (covers consultancy services provided to Amicus Therapeutics Pty Ltd, Ascendis Pharma, Biomarin, Catabasis, Faraday, FibroGen, Genethon, Italfarmaco, NS Pharma, Pfizer, PTC Therapeutics, QED Therapeutics Ltd, Reveragen, Sarepta Therapeutics), outside the submitted work. Michael McDermott has been supported by a research grant from PTC Therapeutics, has received compensation for consulting from Fulcrum Therapeutics, Inc., and NeuroDerm, Ltd., and has served on Data and Safety Monitoring Boards (DSMBs) for AstraZeneca, Eli Lilly and Company, Catabasis Pharmaceuticals, Inc., Vaccinex, Inc., Cynapsus Therapeutics, Neurocrine Biosciences, Inc., Voyager Therapeutics, Prilenia Therapeutics Development, Ltd., ReveraGen BioPharma, Inc., and NS Pharma, Inc. Michelle Eagle is Managing Director at ATOM International Limited and is contracted with the following companies through ATOM: Amicus, Biomarin, Capricor, Catabasis, Denali, Dyne, Edgewise, Faraday, Fibrogen, Genethon, Italfarmaco, Lysogen, Modis, NSPharma, PTC, Sarepta, Solid, Referagen. Robert Griggs receives research support from the NIH, the Muscular Dystrophy Association, the Parent Project for Muscular Dystrophy, and from Sarepta Biopharma, PTC Therapeutics and Santhera Pharmaceuticals. He serves as a Consultant for Strongbridge and Stealth Pharmaceuticals. He is Chair of a DSMB for Solid Pharmaceuticals. He receives monies for editorial work from Elsevier as an Editor of Cecil Essentials and Cecil Textbook of Medicine. He serves as Chair of the Research Advisory Committee and is a Board Member of the American Brain Foundation. He is on the Executive Committee of the Muscle Study Group, which receives support for its activities from Pharmaceutical companies. Meredith K. James provides consultancy services for the following companies: ATOM International (covers consultancy services provided to Amicus Therapeutics Pty Ltd, Ascendis Pharma, Biomarin, Catabasis, Faraday, FibroGen, Genethon, Italfarmaco, NS Pharma, Pfizer, PTC Therapeutics, QED Therapeutics Ltd, Reveragen, Sarepta Therapeutics), outside the submitted work. MKJ has received payment for participation on advisory boards for F. Hoffman La Roche AG, PTC Therapeutics and fee support for PhD studies from the Jain Foundation, outside the submitted work. Robert Muni-Lofra has participated in the advisory board for Biogen and Roche and performs consultancy work (training physiotherapists for trial in DMD and SMA) for Roche, Pfizer, PTC, Summit, Sarepta, Italfarmaco, Amicus, Biogen and Avexis. Lindsey Pallant has performed consultancy work (workshops and training physiotherapists in trials for DMD) for PTC and Sarepta. Katy Eichinger has received personal compensation for serving on advisory boards and/or as a consultant for Ionis, Biogen, Acceleron, Fulcrum, Avidity, PTC and the Myotonic Dystrophy Foundation. Dr. Eichinger has received personal compensation for serving as a speaker from Cure SMA, FSH Society, and Ology. She has received research/grant support from the CMTA. Heather McMurchie has received financial support from PTC and Biogen to access and provide training. Marina DiMarco attended a World Muscle Society conference sponsored by PTC Therapeutics and is a Consultant Physiotherapist presenting at PTC workshops. Lindsay N. Alfano provides consultancy services through ATOM International, Ltd for the following companies: Amicus Therapeutics Pty Ltd, Catabasis, Genethon, Italfarmaco, NS Pharma, Pfizer, PTC Therapeutics); reports royalties and other support from Sarepta Therapeutics; royalties for licensed technologies; other support from Novartis Gene Therapies; advisory board for Biogen. Linda P. Lowes provides consultancy services through ATOM International, Ltd for the following companies: Amicus Therapeutics Pty Ltd, Catabasis, Genethon, Italfarmaco, NS Pharma, Pfizer, PTC Therapeutics); reports royalties and other support from Sarepta Therapeutics; royalties for licensed technologies; other support from Novartis Gene Therapies; advisory board for Biogen. Amy Pasternak has participated in advisory boards for Roche, Biogen, Avexis, Scholar Rock and Audentes. Victoria Kern has received an honorarium from the MDA USA for a presentation. Cheryl Scholtes has sat on advisor panels for Biogen Canada and Roche Canada, and has been provided education on behalf of Biogen Canada and Roche Canada. Catherine Lacroix has acted as a consultant and advisory board participant to Biogen. Katherine Kundrat has participated in an advisory board for Biogen. Michela Guglieri is the study chair for a ReveraGen study. MG has research collaborations with ReveraGen and Sarepta. MG is (has been over the past 5 years) PI for clinical trials sponsored by Pfizer, Italfarmaco, Santhera, ReveraGen, Dynacure, Roche, PTC, Summit. MG has been participating in advisory boards for Pfizer, NS Pharma, Dyne (consultancies through Newcastle University). MG has performed consultancy work (speaker) for Sarepta. Declarations of interest: none for remaining authors, (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)