home-based-monitor-for-gait-and-activity-analysis

Home-Based Monitor for Gait and Activity Analysis

Current outcomes in neuromuscular disorder clinical trials include motor function scales, timed tests, and strength measures performed by trained clinical ...

Institut de Myologie

Myotonic Dystrophy type I (DM1) is caused by an abnormal expansion of CTG triplets in the 3' UTR of the dystrophia myotonica protein kinase (DMPK) gene, leading to the aggregation of the mutant transcript in nuclear RNA foci. The expanded mutant transcript promotes the sequestration of the MBNL1 splicing factor, resulting in the misregulation of a subset of alternative splicing events. In this study, we identify the DEAD-box RNA helicase p68 (DDX5) in complexes assembled onto in vitro-transcribed CUG repeats. We showed that p68 colocalized with RNA foci in cells expressing the 3'UTR of the DMPK gene containing expanded CTG repeats. We found that p68 increased MBNL1 binding onto pathological repeats and the stem-loop structure regulatory element within the cardiac Troponin T (TNNT2) pre-mRNA, splicing of which is misregulated in DM1. Mutations in the helicase core of p68 prevented both the stimulatory effect of the protein on MBNL1 binding and the colocalization of p68 with CUG repeats, suggesting that remodeling of RNA secondary structure by p68 facilitates MBNL1 binding. We also found that the competence of p68 for regulating TNNT2 exon 5 inclusion depended on the integrity of MBNL1 binding sites. We propose that p68 acts as a modifier of MBNL1 activity on splicing targets and pathogenic RNA.

New function for the RNA helicase p68/DDX5 as a modifier of MBNL1 activity on expanded CUG repeats.

Measurement of muscle strength and activity of upper limbs of non-ambulant patients with neuromuscular diseases is a major challenge. ActiMyo® is an innovative device that uses magneto-inertial sensors to record angular velocities and linear accelerations that can be used over long periods of time in the home environment. The device was designed to insure long-term stability and good signal to noise ratio, even for very weak movements. In order to determine relevant and pertinent clinical variables with potential for use as outcome measures in clinical trials or to guide therapy decisions, we performed a pilot study in non-ambulant neuromuscular patients. We report here data from seven Duchenne Muscular Dystrophy (DMD) patients (mean age 18.5 ± 5.5 years) collected in a clinical setting. Patients were assessed while wearing the device during performance of validated tasks (MoviPlate, Box and Block test and Minnesota test) and tasks mimicking daily living. The ActiMyo® sensors were placed on the wrists during all the tests. Software designed for use with the device computed several variables to qualify and quantify muscular activity in the non-ambulant subjects. Four variables representative of upper limb activity were studied: the rotation rate, the ratio of the vertical component in the overall acceleration, the hand elevation rate, and an estimate of the power of the upper limb. The correlations between clinical data and physical activity and the ActiMyo® movement parameters were analyzed. The mean of the rotation rate and mean of the elevation rate appeared promising since these variables had the best reliability scores and correlations with task scores. Parameters could be computed even in a patient with a Brooke functional score of 6. The variables chosen are good candidates as potential outcome measures in non-ambulant patients with Duchenne Muscular Dystrophy and use of the ActiMyo® is currently being explored in home environment.

A Movement Monitor Based on Magneto-Inertial Sensors for Non-Ambulant Patients with Duchenne Muscular Dystrophy: A Pilot Study in Controlled Environment.

Article	Year
New function for the RNA helicase p68/DDX5 as a modifier of MBNL1 activity on expanded CUG repeats. Nucleic acids research\| PubMed ID: 22156369	2012
A Movement Monitor Based on Magneto-Inertial Sensors for Non-Ambulant Patients with Duchenne Muscular Dystrophy: A Pilot Study in Controlled Environment. PloS one\| PubMed ID: 27271157	2016

Erwan Gasnier

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