Author Profile

Jerry R. Mendell

Affiliation: Departments of Neurology and Pediatrics, The Ohio State University, Columbus, Ohio, USA; Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA

Recent Posts

A Randomized, Double-Blind Trial of Lisinopril and Losartan for the Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy

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Objectives:
This study sought to compare the effectiveness and safety of an angiotensin converting enzyme inhibitor (ACE-I) (lisinopril) vs. an angiotensin receptor blocker (ARB) (losartan) for the treatment of cardiomyopathy (CM) in boys with Duchenne muscular dystrophy (DMD).

Background:
Development of CM is universal in boys with DMD. ACE-I and ARB have both been suggested as effective treatment options. ARBs have been associated with skeletal muscle regeneration in a mouse model of DMD. The question of which, if either, is more effective for CM treatment in DMD remains. The purpose of this multicenter double-blind prospective study was to compare efficacy and safety of lisinopril versus losartan in the treatment of newly diagnosed CM in boys with DMD.

Methods:
Echocardiographic technician inter- and intraobserver variability were tested on 2 separate days on 2 different boys with DMD CM. Results were compared with paired t-testing.
Twenty-two boys with newly diagnosed DMD CM (echocardiographic ejection fraction (EF) 10% EF drop. Three boys in the aCE-I group had 3 visits, due to study funding termination. Two were withdrawn because of low EF. All their data are included in the analysis for as long as they remained in the study. Mean EF’s were similar at baseline (47.5%- ACE-I, 48.4%- ARB). After 1 year each group significantly improved to 54.6% and 55.2% respectively (p=.02). There was no difference between the 2 treatment groups at 1 year.

Conclusions:
Inter-observer and intra-observer reliability studies showed no differences between echocardiographers on serial examinations.
EF improved equally in the two groups. There is no therapeutic difference in EF improvement between lisinopril and losartan over the one-year duration for treatment of boys with DMD-related CM.

Trial Registration:
ClinicalTrials.gov NCT01982695

Proof of Concept of the Ability of the Kinect to Quantify Upper Extremity Function in Dystrophinopathy

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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.