A placebo-controlled trial of gabapentin in spinal muscular atrophy

Miller, Robert G.; Moore, Dan H.; Dronsky, V.; Bradley, Walter G.; Barohn, Richard J.; Bryan, Wilson W.; Prior, Thomas W.; Gelinas, Deborah; Iannaccone, Susan T.; Kissel, John T.; Leshner, Robert T.; Mendell, Jerry R.; Mendoza, Michelle C.; Russman, Barry S.; Samaha, Frederick J.; Smith, Stephen A.

doi:10.1016/s0022-510x(01)00632-3

Cited by 87 publications

(68 citation statements)

References 13 publications

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“…A large, phase II trial of TCH346 in ALS showed a trend toward detriment on most outcome measures assessed but no effect on MMT [7]. Other studies have employed MMT testing in ALS, spinobulbar muscular atrophy, and spinal muscular atrophy (SMA) [8][9][10][11][12]. However, in most studies, no therapeutic benefit was noted with any outcome measure, so that the relative sensitivity of MMT testing compared with other measures could not be assessed.…”

Section: Methods Of Strength Assessment Manual Muscle Testingmentioning

confidence: 99%

Strength Testing in Motor Neuron Diseases

Shefner

2017

Neurotherapeutics

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Loss of muscle strength is a cardinal feature of all motor neuron diseases. Functional loss over time, including respiratory dysfunction, inability to ambulate, loss of ability to perform activities of daily living, and others are due, in large part, to decline in strength. Thus, the accurate measurement of limb muscle strength is essential in therapeutic trials to best understand the impact of therapy on vital function. While qualitative strength measurements show declines over time, the lack of reproducibility and linearity of measurement make qualitative techniques inadequate. A variety of quantitative measures have been developed; all have both positive attributes and limitations. However, with careful training and reliability testing, quantitative measures have proven to be reliable and sensitive indicators of both disease progression and the impact of experimental therapy. Quantitative strength measurements have demonstrated potentially important therapeutic effects in both amyotrophic lateral sclerosis and spinobulbar muscular atrophy, and have been shown feasible in children with spinal muscular atrophy. The spectrum of both qualitative and quantitative strength measurements are reviewed and their utility examined in this review.

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Section: Methods Of Strength Assessment Manual Muscle Testingmentioning

confidence: 99%

Strength Testing in Motor Neuron Diseases

Shefner

2017

Neurotherapeutics

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“…Three clinical trials for SMA patients have been performed. Gabapentin, a likely neuroprotective agent, did not lead to differences in the outcome measure, 12 whereas, in pilot trials using thyrotropin-releasing hormone and albuterol, improvement of muscle strength in a small number of type II and III patients has been reported. 13,14 None of these drugs appears to act on the molecular defect.…”

Section: Introductionmentioning

confidence: 94%

Phenylbutyrate increases SMN expression in vitro: relevance for treatment of spinal muscular atrophy

et al. 2003

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Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease, characterized by degeneration of the anterior horn cells of the spinal cord. SMA presents with a highly variable phenotype ranging from very severe to mild (type I-III). No cure for SMA is available at present. All forms of SMA are caused by homozygous loss of the functional survival motor neuron (SMN1) gene. However, all patients have one or more copies of the SMN2 gene, nearly identical to SMN1. Both genes encode the SMN protein but the level produced by SMN2 is insufficient to protect from disease. Increasing SMN2 gene expression could be of considerable therapeutic importance. The aim of this study was to assess whether SMN2 gene expression can be increased by 4-phenylbutyrate (PBA). Fibroblast cell cultures from 16 SMA patients affected by different clinical severities were treated with PBA, and full-length SMN2 transcripts were measured by real-time PCR. In all cell cultures, except one, PBA treatment caused an increase in full-length SMN2 transcripts, ranging from 50 to 160% in type I and from 80 to 400% in type II and III cultures. PBA was found also effective in enhancing SMN protein levels and the number of SMN-containing nuclear structures (gems). These data show that SMN expression is considerably increased by PBA, and suggest that the compound, owing also to its favorable pharmacological properties, could be a good candidate for the treatment of SMA.

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“…Miller et al [6], Merlini et al [5,7,8] and others [9] have established the reliability and validity of myometry in the assessment of strength in children with SMA, but only in those older than age 5. On the other hand, functional motor scales may be more appropriate for young children, as motivation for maximum performance need not depend upon comprehension of the purpose of the task.…”

Section: Introductionmentioning

confidence: 99%

“…More recently the EK scale [20] was developed for non-ambulatory patients with Duchenne's muscular dystrophy (DMD) and SMA, the Wee Fim was utilized to quantify function in children with SMA in Hong Kong [11] and the functional research scale for ALS (FRS-ALS) scale was utilized in clinical trials with adult patients with ALS [21,22]. These scales are typically used as primary outcome measures for a treatment trial only when direct measure of power is not possible, though their use as a secondary measure is common [5,6,[23][24][25][26]. Though each of these tests were developed to assess functional skills in weak patients with neuromuscular disorders, construct of test items often precludes their use in assessing younger children.…”

Section: Introductionmentioning

confidence: 99%

A modified Hammersmith functional motor scale for use in multi-center research on spinal muscular atrophy

Krosschell

Maczulski²,

Crawford

et al. 2006

Neuromuscular Disorders

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The Hammersmith functional motor scale for children with spinal muscular atrophy was modified to establish a standard measure of functional ability in children with non-ambulant spinal muscular atrophy types 2 and 3 in a longitudinal multi-center clinical trial. This study assessed the intra-and interrater reliability and the test-retest stability of a modified version of the scale. Both intra-and interrater reliability were established. Results indicate that the scale is reliable and stable over a 6 month period. Reliability was maintained when patient sample criteria were expanded to include children younger than 30 months and children with popliteal angles greater than 20°. These data establish the modified Hammersmith functional motor scale for children with spinal muscular atrophy as a reliable instrument for use in multi-center treatment trials in non-ambulant spinal muscular atrophy children. Our data provides additional support for the use of original scale items in terms of ease of administration, usefulness and reliability, while incorporating modifications to optimize its use in a multi-center clinical research setting.

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A placebo-controlled trial of gabapentin in spinal muscular atrophy

Cited by 87 publications

References 13 publications

Strength Testing in Motor Neuron Diseases

Strength Testing in Motor Neuron Diseases

Phenylbutyrate increases SMN expression in vitro: relevance for treatment of spinal muscular atrophy

A modified Hammersmith functional motor scale for use in multi-center research on spinal muscular atrophy

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