Our Research

Mechanisms and Treatment of Exercise Intolerance and Persistent Fatigue in Spinal Muscular Atrophy

This study will focus on the pathophysiological underpinnings of reduced exercise capacity and fatigue in ambulatory patients with spinal muscular atrophy (SMA). There has been laboratory evidence to suggest that the molecular mechanisms underlying mitochondrial biogenesis may be vulnerable to survival motor neuron (SMN) protein deficiency. This is an observational, single visit study including 34 ambulatory SMA patients treated with SMN repletion therapies (risdiplam or nusinersen) for at least 6 months at enrollment.

Learn More at clinicaltrials.gov

SMA EFFORT: A New Approach to Perceived Physical Fatigability Assessment in Spinal Muscular Atrophy

Fatigue and fatigability are symptoms impacting the well-being of people living with spinal muscular atrophy (pwSMA). Approved therapies extend survival and improve motor function, but fatigue and fatigability persist. Treated patients report changes in their ability to execute repetitive physical tasks but a method for quantifying it has not been established. While performance-based outcome measures highlight fatigability as a disease hallmark, perceived physical fatigability (PPF) has not been well characterized in SMA.  This project investigates the utility of a disease-specific Experienced Fatigability Rating Tool, the SMA EFFORT. We aim to characterize PPF in a diverse cohort of pwSMA and evaluate the psychometric properties of the scale. We hypothesize that the SMA EFFORT will capture PPF within and between individuals of differing abilities and demonstrate strong psychometric properties. 

Establishing Walking-related Digital Biomarkers in Rare Childhood Onset Progressive Neuromuscular Disorders

Recent therapeutic approaches for individuals with neuromuscular disorders (NMD) have resulted in disease modifying therapies but benefits reported by patients, experienced in real-world settings, often elude the standard in-clinic examination. Emerging wearable devices allow for ubiquitous monitoring of physical mobility, but their widespread use in clinical applications is currently hampered by their moderate granularity and accuracy. This research aims to implement novel foot-worn devices that can accurately measure stride-by-stride spatiotemporal and kinetic gait parameters, which can be used as sensitive digital mobility outcomes (DMO) to reflect real-world ambulatory function in individuals with childhood onset NMD.

Natural History Studies of Rare Genetic Neurodevelopmental Disorders 

With advancements in genetic testing, such as whole exome sequencing, there is an increasing number of rare genetic disorders that are being identified. Further, newborn screening initiatives help to identify these disorders even earlier with the goal of earlier access to therapeutic intervention for improved outcomes. This research in collaboration with Dr. Wendy Chung, aims to better characterize rare genetic neurodevelopmental disorders in order to understand natural disease history to be best equipped to monitor change in upcoming clinical trials and in eventual real-world scenarios with future therapeutics. Since developmental delay is a key symptom across disorders, monitoring motor function is essential. 

Assessments of  Muscle Composition and Function and their Association to Bone Mineral Density in Spinal Muscular Atrophy 

Bone mineral density (BMD), a measure of the mineral content in bones, can identify low bone mass (LBM). In addition to age and hormonal status, other factors that contribute to LBM, include muscle weakness and decreased weight bearing opportunities resulting in increased fracture risk. Lean body mass is a strong predictor of BMD in healthy populations. Mobility limitations have largely been attributed to decreased BMD in SMA though pre-clinical data supports that there is an SMN requirement in bone turnover or resorption. Consequences of SMA, including those related to decreased SMN protein, muscle weakness, and altered mobility can lead to LBM and are potential targets for intervention. Since indirect measures of muscle have been found to be associated with BMD in healthy and SMA groups, studying muscle composition and architecture to further understand its association with BMD may be informative. This may lead to the identification of muscle related targets for therapeutic and rehabilitative interventions.