Salbutamol tolerability and efficacy in patients with spinal muscular atrophy type II

Frongia, A.; Benito, Daniel Natera-de; Ortez, C.; Alarcón, M.; Borrás, A; Medina, J.; Vigo, M.; Padros, Nuria; Moya, O.; Armas, Jácome Bruges; Carrera‐García, Laura; Expósito‐Escudero, Jessica; Cuadras, Daniel; Bernal, Sara; Martorell, Loreto; Colomer, J.; Nascimento, A.

doi:10.1016/j.nmd.2019.04.003

Cited by 17 publications

(19 citation statements)

References 41 publications

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“…Although its content validity and clinical meaningfulness has been shown in adult SMA patients, 17 its construct validity has not been formally assessed in adult SMA patients. Consistently with previous results in children, 14,16,32 we found that HFMSE strongly correlates with other motor function and bedside functional scales, and discriminated well between sitters and walkers, suggesting its convergent and discriminant validity also in adult patients. However, it correlated only moderately with FVC%, suggesting less convergent validity in more severely affected patients (weakest sitters).…”

Section: Hfmsesupporting

confidence: 91%

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Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy

Vázquez-Costa

Povedano

et al. 2021

Preprint

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Objective To assess in adult spinal muscular atrophy (SMA) patients the construct validity and responsiveness of several outcome measures. Methods Patients older than 15 years and followed-up at least for 6 months, between October 2015 and August 2020, with one motor function scale (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb module, RULM) in five referral centers were included. Bedside functional scales (Egen Klassification, EK2; Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, ALSFRS-R) were also collected when available. Correlations and regression models were performed to evaluate the construct validity. The monthly slopes of change were used to calculate their responsiveness. Results The study included 79 SMA patients, followed up for a mean of 16 months. All scales showed strong or very strong correlations with each other. A floor effect in motor function scales was found in weakest patients (HFMSE < 5 and RULM<10), and a ceiling effect in stronger patients (with HFMSE >55 and RULM > 35), when compared with other scales. ALSFRS-R (B=0.72) showed a strong discriminating ability between walkers, sitters, and non-sitters, and HFMSE (B=0.86) between walkers and sitters. The responsiveness was overall low, although in treated patients a moderate responsiveness was found for ALSFRS-R and HFMSE in walkers (0.69 and 0.61 respectively), and for EK2 in sitters (0.65) and non-sitters (0.60). Conclusions This study shows the validity in SMA adult patients of commonly used scales. Overall, bedside functional scales showed some advantages over motor function scales, although all scales showed low responsiveness in untreated patients.

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Section: Hfmsesupporting

confidence: 91%

“…Functional Rating Scale (SMAFRS) are the most frequently used bedside functional scales in adult SMA patients.3 They are reliable, fast, and easy to use, but data on their construct validity and responsiveness (i.e. sensitivity to change) in adult SMA patients are lacking or scarce.7,10,12,14 …”

mentioning

confidence: 99%

Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy

Vázquez-Costa

Povedano

et al. 2021

Preprint

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“…109 Salbutamol, a b2-adrenoreceptor agonist, modestly improves muscle strength in patients by increasing levels of SMN2 fulllength mRNA and protein 110 and possibly through stabilization of acetylcholine receptor clusters at the NMJ. 111 Although small clinical studies suggest that it could help maintaining motor function 64 or improve respiratory function 112 of SMA type 2 patients, large-scale, placebo-controlled studies are lacking.…”

Section: Bioenergeticsmentioning

confidence: 99%

Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine

Chaytow

Faller

Huang

et al. 2021

Cell Reports Medicine

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Spinal muscular atrophy (SMA) is a devastating childhood motor neuron disease that, in the most severe cases and when left untreated, leads to death within the first two years of life. Recent therapeutic advances have given hope to families and patients by compensating for the deficiency in survival motor neuron (SMN) protein via gene therapy or other genetic manipulation. However, it is now apparent that none of these therapies will cure SMA alone. In this review, we discuss the three currently licensed therapies for SMA, briefly highlighting their respective advantages and disadvantages, before considering alternative approaches to increasing SMN protein levels. We then explore recent preclinical research that is identifying and targeting dysregulated pathways secondary to, or independent of, SMN deficiency that may provide adjunctive opportunities for SMA. These additional therapies are likely to be key for the development of treatments that are effective across the lifespan of SMA patients.

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“…It has been shown that Salbutamol determines a rapid and significant increase of FL-SMN mRNA and protein in SMA fibroblasts, predominantly by promoting exon seven inclusion in SMN2 transcripts (Angelozzi et al, 2008): these results were further confirmed in peripheral blood leukocytes of SMA type II-III patients (Tiziano et al, 2010). Moreover, when administered to SMA type II and III patients, Salbutamol induced an overall improvement of motor performances and lung/inspiratory functions and a reduction of the perceived fatigue, suggesting further studies on the molecular mechanisms underlying these effects and its influence on muscles and NMJs (Pane et al, 2008;McCullagh et al, 2011;Giovannetti et al, 2016;Khirani et al, 2017;Frongia et al, 2019;Wadman et al, 2020).…”

Section: Neuromuscular Junction Stabilizationmentioning

confidence: 73%

Drug Screening and Drug Repositioning as Promising Therapeutic Approaches for Spinal Muscular Atrophy Treatment

et al. 2020

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Salbutamol tolerability and efficacy in patients with spinal muscular atrophy type II

Cited by 17 publications

References 41 publications

Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy

Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy

Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine

Drug Screening and Drug Repositioning as Promising Therapeutic Approaches for Spinal Muscular Atrophy Treatment

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