The purpose of this study was to examine the correlations between change scores on the Manual Muscle Test for muscle strength and the Gross Motor Function Measure for motor function in individuals with spinal muscular atrophy type 2 and type 3. The specific aims were to reveal any differences in correlations between younger (children) and older (adolescents and adults) individuals and also between walkers and nonwalkers with spinal muscular atrophy.
A total of 56 individuals with spinal muscular atrophy aged 5 to 41 yrs were recruited. Muscle strength and motor function were measured three times at 6-mo intervals. The Manual Muscle Test scores of 36 muscle groups and Gross Motor Function Measure scores were obtained. Differences in these scores over time (baseline to 6 mos and baseline to 12 mos) were calculated.
Changes in Manual Muscle Test scores correlated positively to changes in Gross Motor Function Measure scores over 12 mos (r = 0.35, P = 0.01). Significantly positive correlations between the change scores over 12 mos were evident in the older group (r = 0.48, P = 0.02) and in nonwalkers (r = 0.47, P < 0.001).
The correlations between change scores on Manual Muscle Test and on Gross Motor Function Measure suggest that these two measures are suitable for representing concurrent changes in muscle strength and motor function in spinal muscular atrophy within 12 mos.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Antisense oligonucleotide (AON) therapy is a form of treatment for genetic or infectious diseases using small, synthetic DNA-like molecules called AONs. Recent advances in the development of AONs that show improved stability and increased sequence specificity have led to clinical trials for several neuromuscular diseases. Impressive preclinical and clinical data are published regarding the usage of AONs in exon-skipping and splice modulation strategies to increase dystrophin production in Duchenne muscular dystrophy (DMD) and survival of motor neuron (SMN) production in spinal muscular atrophy (SMA).
In this review, we focus on the current progress and challenges of exon-skipping and splice modulation therapies. In addition, we discuss the recent failure of the Phase III clinical trials of exon 51 skipping (drisapersen) for DMD.
The main approach of AON therapy in DMD and SMA is to rescue ('knock up' or increase) target proteins through exon skipping or exon inclusion; conversely, most conventional antisense drugs are designed to knock down (inhibit) the target. Encouraging preclinical data using this 'knock up' approach are also reported to rescue dysferlinopathies, including limb-girdle muscular dystrophy type 2B, Miyoshi myopathy, distal myopathy with anterior tibial onset and Fukuyama congenital muscular dystrophy.
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