A5023381652- Neurogenetic and Muscular Disorders Research
- Congenital Anomalies and Fetal Surgery
- RNA modifications and cancer
- Muscle Physiology and Disorders
- Family and Disability Support Research
- Cardiac Structural Anomalies and Repair
- Cardiomyopathy and Myosin Studies
- Cerebral Palsy and Movement Disorders
- Amyotrophic Lateral Sclerosis Research
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Viral Infections and Immunology Research
- Congenital Heart Disease Studies
- Myasthenia Gravis and Thymoma
- Energy Harvesting in Wireless Networks
- Mechanical Circulatory Support Devices
- Autism Spectrum Disorder Research
- Muscle activation and electromyography studies
- Balance, Gait, and Falls Prevention
- Prosthetics and Rehabilitation Robotics
- Cardiovascular and exercise physiology
- Tracheal and airway disorders
- Long-Term Effects of COVID-19
- Retinal Diseases and Treatments
- Dysphagia Assessment and Management
Stanford University
2019-2025
Merck & Co., Inc., Rahway, NJ, USA (United States)
2025
Boston Children's Hospital
2012-2024
Harvard University
2012-2024
Johns Hopkins University
2024
The University of Texas Southwestern Medical Center
2024
Pfizer (United States)
2024
American Physical Therapy Association
2024
Scholar Rock (United States)
2024
Palo Alto University
2019-2024
Prospective cohort study to characterize the clinical features and course of spinal muscular atrophy type I (SMA-I).Patients were enrolled at 3 sites followed for up 36 months with serial clinical, motor function, laboratory, electrophysiologic outcome assessments. Intervention was determined by published standard care guidelines. Palliative options offered.Thirty-four 54 eligible subjects SMA-I (63%) 50% these completed least 12 follow-up. The median age reaching combined endpoint death or...
ABSTRACT Introduction There is a growing need for robust clinical measure to assess upper limb motor function in spinal muscular atrophy (SMA), as the available scales lack sensitivity at extremes of spectrum. We report development Revised Upper Limb Module (RULM), an assessment specifically designed SMA patients. Methods An international panel with specific neuromuscular expertise performed thorough review currently SMA. This facilitated revision existing make more scale. Results Multiple...
To characterize the natural history of spinal muscular atrophy type 2 and 3 (SMA 2/3) beyond 1 year to report data on clinical biological outcomes for use in trial planning.
In spinal muscular atrophy (SMA), weakness, decreased endurance, and fatigue limit mobility. Scales have been developed to measure function across the wide spectrum of disease severity. However, these scales typically are observer dependent, scores based on sums Likert-scaled items. The Six-Minute Walk Test (6MWT) is an objective, easily administered, standardized evaluation functional exercise capacity that has proven reliable in other neurologic disorders children.To study performance 6MWT...
The relationships between the Expanded Hammersmith Functional Motor Scale (HFMSE) and genotype motor respiratory outcomes were examined in patients with spinal muscular atrophy types II III ( n = 70). correlation HFMSE Gross Function Measure was r 0.98. Correlations forced vital capacity (percentage of predicted normal) 56) a functional rating 57) 0.87 0.92, respectively. strength as follows: knee extension, 0.74 60); elbow flexion, 0.77 61); 58). differentiated by SMN2 copy number P .0007);...
The aim of the study was to establish 12-month changes in Hammersmith Functional motor scale a large cohort SMA patients, identify patterns disease progression and effect different variables. 268 patients were included this multicentric study. Their age ranged between 2.5 55.5 years at baseline, 68 ambulant 200 non-ambulant. baseline scores 0 66 (mean 23.91, SD 20.09). change −14 +9 −0.56, 2.72). Of 206 (76.86%) had −2 +2 points. Ambulant non-ambulant subjects relationship values (p for X...
Reports on the clinical meaningfulness of outcome measures in spinal muscular atrophy (SMA) are rare. In this two-part study, our aim was to explore patients’ and caregivers’ views relevance Hammersmith Functional Motor Scale Expanded- (HFMSE). First, we used focus groups including SMA patients caregivers their individual activities included HFMSE. Then asked comment possible changes HFMSE scores over time. As functional data were available, some questions tailored according level Part 1:...
Recent translational research developments in Spinal Muscular Atrophy (SMA), outcome measure design and demands from regulatory authorities require that clinical assessments are 'fit for purpose'. An international collaboration (SMA REACH UK, Italian SMA Network PNCRN USA) undertook an iterative process to address discontinuity the recorded performance of Hammersmith Functional Motor Scale Expanded developed a revised functional scale using Rasch analysis, traditional psychometric techniques...
In Brief Purpose: Preliminary validation of the Children's Hospital Philadelphia Infant Test Neuromuscular Disorders (CHOP INTEND) for motor skill assessment in spinal muscular atrophy type I. Methods: A total 27 subjects 3 to 260 months old (mean = 49, SD 69) with atrophy–I were evaluated CHOP INTEND. Subjects as part a multicenter natural history study. Results: INTEND scores and age significantly correlated (r −0.51, P .007; 2 survival neuron [SMN] gene copies, n 16, r −0.60, SMN2 9,...
PurposeTo determine feasibility and utility of newborn screening for spinal muscular atrophy (SMA) in New York State.MethodsWe validated a multiplex TaqMan real-time quantitative polymerase chain reaction assay using dried blood spots SMA. From January 2016 to 2017, we offered, consented, screened 3,826 newborns at three hospitals City tested the deletion exon 7 SMN1.ResultsNinety-three percent parents opted SMA screening. Overall carrier frequency was 1.5%. We identified one with homozygous...
The Six-Minute Walk Test (6MWT) was adopted as a clinical outcome measure for ambulatory spinal muscular atrophy (SMA). However, systematic review of measurement properties reported significant variation among chronic pediatric conditions. Our purpose to assess the reliability/validity 6MWT in SMA.Thirty participants performed assessments, including 6MWT, strength, and function. Reproducibility evaluated by intraclass correlation coefficients. Criterion/convergent validity were determined...
The aim of this retrospective multicentric study was to assess developmental milestones longitudinally in type I SMA infants using the Hammersmith Infant Neurological Examination. Thirty-three infants, who classically do not achieve ability sit unsupported, were included study. Our results confirmed that all patients had a score 0 out scale 4 on items assessing sitting, rolling, crawling, standing or walking. A more than only achieved three items: head control (n = 13), kicking 15) and hand...
The aim of the study was to assess 12 month changes in upper limb function patients affected by spinal muscular atrophy type 2 and 3.Longitudinal data collected 114 patients, 60 54 3, using Revised Upper Limb Module.The ranged between -7 9 (mean: -0.41; SD: 2.93). mean were not significantly different three groups (-0.45 2, -0.23 non-ambulant 3 -0.34 ambulant p = 0.96) relationship change age classes among types SMA patients.Our results confirm that Module explores a wide range functional...
Abstract Introduction Ambulatory individuals with spinal muscular atrophy (SMA) experience muscle weakness, gait impairments, and fatigue that affect their walking ability. Improvements have been observed in motor function children treated nusinersen, but its impact on has not studied. Methods Post hoc analyses were used to examine changes 6‐minute walk test (6MWT) distance adolescents SMA type II III who received first dose of nusinersen the phase Ib/IIa, open‐label CS2 study ambulatory...
Currently approved therapies for spinal muscular atrophy (SMA) reverse the degenerative course, leading to better functional outcome, but they do not address impairment arising from preexisting neurodegeneration. Apitegromab, an investigational, fully human monoclonal antibody, inhibits activation of myostatin (a negative regulator skeletal muscle growth), thereby preserving mass. The phase 2 TOPAZ trial assessed safety and efficacy apitegromab in individuals with later-onset type 3 SMA.
Individuals with spinal muscular atrophy (SMA) type 3 are able to walk but they have weakness, gait impairments and fatigue. Our primary study objective was examine longitudinal changes in the six-minute test (6MWT) evaluate whether age SMA subtype associated decline ambulatory function. Data from three prospective natural history studies were used. Seventy-three participants who performed 6MWT more than once, at least 6 months apart, included; follow-up ranged 0.5–9 years. Only data...
To determine changes in motor and respiratory function after treatment with nusinersen adults spinal muscular atrophy (SMA) during the first two years of commercial availability USA.Data were collected prospectively on adult (age >17 at initiation) SMA participants Pediatric Neuromuscular Clinical Research (PNCR) Network. Baseline assessments outcomes including Expanded Hammersmith Functional Rating Scale (HFMSE), Revised Upper Limb Module (RULM), 6-Minute Walk Test (6MWT) occurred <5 months...
Spinal muscular atrophy (SMA) is a neuromuscular disorder characterised by progressive motor function decline. Motor assessed using several functional outcome measures including the Revised Hammersmith Scale (RHS).
Background: Training methodology was established to optimize reliability of outcome measures in the nusinersen clinical trials.The Children's Hospital Philadelphia Infant Test Neuromuscular Disorders (CHOP INTEND), Hammersmith Functional Motor Scale Expanded (HFMSE), and Revised Upper Limb (RULM) were primary or secondary outcomes.Methods: Video review, quarterly conference calls, item scoring checks supported evaluator competence.Baseline screening along with video review intra inter-rater...
Objective We report natural history data in a large cohort of 199 patients with spinal muscular atrophy (SMA) type III assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE). The aim study was to establish annual rate and possible patterns progression according number variables, such as age onset, at assessment, SMN2 copy number, functional status. Methods HFMSE longitudinal changes were piecewise linear mixed‐effects models. dependency due repeated measures accounted for by...
Abstract Objective We report longitudinal data from 144 type III SMA pediatric and adult patients treated with nusinersen as part of an international effort. Methods Patients were assessed using Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), 6‐Minute Walk Test (6MWT) a mean follow‐up 1.83 years after treatment. Results Over 75% the had 12‐month follow‐up. There was increase in scores baseline to 12 months on both HFMSE (1.18 points, p = 0.004) RULM...
Improvement and maintenance of bulbar function are goals disease-modifying treatments for spinal muscular atrophy (SMA). Lack standardized measures a widely accepted definition represents gap in SMA care.A multidisciplinary team conducted post-hoc analyses pooled data from one phase 1 (START) two 3 (STR1VE-US, STR1VE-EU) studies to define evaluate infants with type after receiving one-time gene replacement therapy, onasemnogene abeparvovec.We defined as the ability meet nutritional needs...