Our Research

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

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 - Currently Recruiting

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. 

Characterizing perceived physical fatigability in nusinersen-treated adolescents and adults: The SMA EFFORT - Currently Recruiting

Physical fatigability are symptoms often experienced by people living with spinal muscular atrophy (pwSMA). While tests completed in the clinic by individuals with SMA highlight that fatigability is an important part of the SMA experience, we do not fully understand how pwSMA experience fatigability with everyday tasks. 

The SMA EFFORT is a patient-reported outcome measure (PROM) specifically designed for pwSMA and aims to better understand how they feel when completing daily physical activities. This self-report questionnaire focuses on the intensity and duration of activities that typically make patients feel tired. This study will incorporate the SMA EFFORT to help us understand the experience of fatigability better in nusinersen treated individuals before after dosing. 

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

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 their association to bone health in spinal muscular atrophy

There are known factors that impact bone health in the general population, such as physical activity, lean muscle mass, and weight bearing opportunities. The impairments associated with strength and function in SMA as well as the requirement of SMN in the bone resorption process makes bone health a warranted concern for people with SMA. Previous studies have focused on non-ambulatory, untreated children, while there is a gap in the understanding of bone health in an era of treatment. Currently approved disease modifying therapies (DMT) target SMN protein levels,but it is unclear what downstream effect this may have on the muscle and bone itself. In preliminary work, we have found that 1) ambulatory individuals with SMA  have low bone mass and 2) indirect measures of muscle are associated with bone mineral density. This study aims to more directly explore muscle composition and its association to bone health in people with SMA who are ambulatory and on DMT. This work may lead to identification of muscle related targets for therapeutic and rehabilitative intervention. It could also lead to earlier identification and intervention for poor bone health which may proactively minimize occurrence of fractures.