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INTRODUCTION: Individuals with dystrophinopathy lose upper extremity strength in proximal muscles followed by those more distal. Current upper extremity evaluation tools fail to fully capture changes in upper extremity strength and function across the disease spectrum as they tend to focus solely on distal ability. The Kinect by Microsoft is a gaming interface that can gather positional information about an individual's upper extremity movement which can be used to determine functional reaching volume, velocity of movement, and rate of fatigue while playing an engaging video game. The purpose of this study was to determine the feasibility of using the Kinect platform to assess upper extremity function in individuals with dystrophinopathy across the spectrum of abilities. METHODS: Investigators developed a proof-of-concept device, ACTIVE (Abilities Captured Through Interactive Video Evaluation), to measure functional reaching volume, movement velocity, and rate of fatigue. Five subjects with dystrophinopathy and 5 normal controls were tested using ACTIVE during one testing session. A single subject with dystrophinopathy was simultaneously tested with ACTIVE and a marker-based motion analysis system to establish preliminary validity of measurements. RESULTS: ACTIVE proof-of-concept ranked the upper extremity abilities of subjects with dystrophinopathy by Brooke score, and also differentiated them from performance of normal controls for the functional reaching volume and velocity tests. Preliminary test-retest reliability of the ACTIVE for 2 sequential trials was excellent for functional reaching volume (ICC=0.986, p<0.001) and velocity trials (ICC=0.963, p<0.001). DISCUSSION: The data from our pilot study with ACTIVE proof-of-concept demonstrates that newly available gaming technology has potential to be used to create a low-cost, widely-accessible and functional upper extremity outcome measure for use with children and adults with dystrophinopathy.
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Neurotrophic factors have been considered as potential therapeutics for peripheral neuropathies. Previously, we showed that neurotrophin-3 (NT-3) promotes nerve regeneration in Trembler(J) (Tr(J)) mice and in sural nerves from patients with Charcot-Marie-Tooth 1A (CMT1A). The relatively short plasma half-life of NT-3 and other neurotrophins, however, pose a practical difficulty in their clinical application. Therapeutic agonist antibodies (AAb) targeting the neurotrophic receptors may circumvent this obstacle due to their high specificity and long half-life. Using morphological, electrophysiological studies and functional motor testing, we assessed the efficacy of monoclonal TrkC AAb and TrkB AAb in the Tr(J) mice. Treatments of these AAbs individually or in combination over 20 weeks increased compound muscle action potential (CMAP) amplitude, which correlated with improved grip strength, as compared to the PBS control group. Improvements in CMAP amplitude were most prominent with TrkC AAb treatment. In all treatment groups, distal to the crush site of the sciatic nerves exhibited a significantly greater number of myelinated fibers (MFs) indicating improved regenerative response to injury. In the contralateral intact sciatic nerves, the number of MFs as well as the myelin thickness was also increased significantly by the AAb treatments, suggesting that the hypomyelination/amyelination state of the peripheral nerves in Tr(J) improved. Therapeutic response to AAb combination was often, albeit not always, the most prominent, indicating a non-redundant effect of TrkB and TrkC AAbs. An early functional recovery and the correlative morphological changes of enhanced regeneration were seen with TrkC AAb treatment. These results provide evidence for potential therapeutic use of monoclonal agonist antibodies for neurotrophin receptors in CMT1A and other neuropathies.