Relationship Between Hand Strength and Function in Duchenne Muscular Dystrophy and Spinal Muscular Atrophy: Implications for Clinical Trials.

Background: Measurement of muscle strength and motor function is recommended in clinical trials of neuromuscular diseases, but the loss of hand strength at which motor function is impacted is not documented.

Objectives: To establish the relationship between hand strength and function, and to determine the strength threshold that differentiates normal and abnormal hand function in individuals with Duchenne Muscular Dystrophy (DMD) or Spinal Muscular Atrophy (SMA).

Methods: Maximal handgrip and key pinch strength were measured with the MyoGrip and MyoPinch dynamometers, respectively.

Effect of sirolimus on muscle in inclusion body myositis observed with magnetic resonance imaging and spectroscopy.

Background: Finding sensitive clinical outcome measures has become crucial in natural history studies and therapeutic trials of neuromuscular disorders. Here, we focus on 1-year longitudinal data from quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (P MRS) in a placebo-controlled study of sirolimus for inclusion body myositis (IBM), also examining their links to functional, strength, and clinical parameters in lower limb muscles.

Methods: Quantitative MRI and P MRS data were collected at 3 T from a single site, involving 44 patients (22 on placebo, 22 on sirolimus) at baseline and year-1, and 21 healthy controls.

GDF5 as a rejuvenating treatment for age-related neuromuscular failure.

Sarcopenia involves a progressive loss of skeletal muscle force, quality and mass during ageing, which results in increased inability and death; however, no cure has been established thus far. Growth differentiation factor 5 (GDF5) has been described to modulate muscle mass maintenance in various contexts. For our proof of concept, we overexpressed GDF5 by AAV vector injection in tibialis anterior muscle of adult aged (20 months) mice and performed molecular and functional analysis of skeletal muscle.

A phase 2 open-label study of the safety and efficacy of weekly dosing of ATL1102 in patients with non-ambulatory Duchenne muscular dystrophy and pharmacology in mdx mice.

Background: ATL1102 is a 2'MOE gapmer antisense oligonucleotide to the CD49d alpha subunit of VLA-4, inhibiting expression of CD49d on lymphocytes, reducing survival, activation and migration to sites of inflammation. Children with DMD have dystrophin deficient muscles susceptible to contraction induced injury, which triggers the immune system, exacerbating muscle damage. CD49d is a biomarker of disease severity in DMD, with increased numbers of high CD49d expressing T cells correlating with more severe and progressive weakess, despite corticosteroid treatment.

Assessment of the upper limb function, strength, and mobility in treatment-naive children with spinal muscular atrophy Types 2 and 3.

Introduction/aims: Current upper limb assessments in pediatric spinal muscular atrophy (SMA) may not adequately capture change with disease progression. Our aim was to examine the relationship between motor function, strength, and hand/finger mobility of the upper limb in treatment-naïve children with SMA Types 2 and 3 to assess new methods to supplement current outcomes.

Methods: The Revised Upper Limb Module (RULM), grip and pinch strength, and hand/finger mobility data were collected from 19 children with SMA Types 2 and 3 aged 5.