Updates in clinical data for FDA-approved disease-modifying therapies for spinal muscular atrophy

Purpose The aim of this study was to provide clinicians with an overview of literature relating to dysphagia in spinal muscular atrophy (SMA) to guide assessment and treatment. Method In this clinical focus article, we review literature published in Scopus and PubMed between 1990 and 2020 pertaining to dysphagia in SMA across the life span. Original research articles that were published in English were included. Searches were conducted within four themes of inquiry: (a) etiology and phenotypes, (b) respiratory systemic deficits and management, (c) characteristics of natural history dysphagia and its treatment, and (d) dysphagia outcomes with disease-modifying therapies. Articles for the first two themes were selected by content experts who identified the most salient articles that would provide clinicians foundational background knowledge about SMA. Articles for the third theme were identified using search terms, including spinal muscular atrophy, swallow, dysphagia, bulbar, nutrition, g-tube, alternative nutrition, jaw, mouth, palate, OR mandible . Search terms for the fourth theme included spinal muscular atrophy AND nusinersen OR AVXS-101/onasemnogene abeparvovec-xioi . Review of Pertinent Literature Twenty-nine articles were identified. Findings across identified articles support the fact that patients with SMA who do not receive disease-modifying therapy exhibit clinically significant deficits in oropharyngeal swallow function. Few investigations provided systematic information regarding the underlying physiological deficits responsible for this loss in function, the timing of the degradation, or how disease-modifying therapies change these outcomes. Conclusion Future research outlining the physiological and functional oropharyngeal swallowing deficits among patients with SMA who receive disease-modifying therapy is critical in developing standards of dysphagia care to guide clinicians.

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Lumbar Puncture Opening Pressure in Patients with Spinal Muscular Atrophy

Neuropediatrics ◽

10.1055/s-0040-1722687 ◽

2021 ◽

Author(s):

Lena-Luise Becker ◽

Claudia Weiß ◽

Anna Tietze ◽

Viktoria Martiny ◽

Angela M. Kaindl

Keyword(s):

Intracranial Pressure ◽

Spinal Muscular Atrophy ◽

Lumbar Puncture ◽

Clinical Data ◽

Side Effect ◽

Treatment Initiation ◽

Muscular Atrophy ◽

Underlying Disease ◽

Increased Intracranial Pressure ◽

Opening Pressure

AbstractThe announcement of a hydrocephalus as a possible side effect in patients with spinal muscular atrophy (SMA) receiving the drug nusinersen, promoted major concern and warrants further evaluation. In this retrospective monocentric study, we analyzed clinical data, lumbar puncture opening pressure (LOP) measurement, and ophthalmologic and neuroimaging results in 34 patients with SMA types 1 to 3 undergoing treatment with nusinersen. None of the patients reported symptoms indicative of increased intracranial pressure. In our cohort, the LOP was >20 cm H2O in 25 patients (70.5%), and within this group ≥28 cm H2O in 12 patients (35.3%), in two patients, it was increased prior to treatment initiation. Signs of increased intracranial pressure in ophthalmological assessments or brain imaging were only seen in one patient. We did not identify a correlation between increased LOP and SMA type, scoliosis, or age of the patients; however, it was slightly higher in patients receiving sedation. Our results raise the question whether the LOP is generally increased in SMA as part of the underlying disease, if so, what the etiology is, and whether the increased LOP needs to be treated.

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HAVING A GO AT SPINAL MUSCULAR ATROPHY WITH SPINRAZA

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i6.17502 ◽

2017 ◽

Vol 10 (6) ◽

pp. 16

Author(s):

Balaji O ◽

Amita D ◽

Sereen Rt ◽

Navin Ap

Keyword(s):

Cystic Fibrosis ◽

Clinical Trials ◽

Spinal Muscular Atrophy ◽

Drug Administration ◽

Muscular Atrophy ◽

Food And Drug Administration ◽

Neurological Condition ◽

Disease Modifying Therapy ◽

Different Types ◽

Disease Modifying

Spinal muscular atrophy (SMA), a neurological condition which is genetically mediated is the second most common infantile disease causing morbidity and mortality next to cystic fibrosis. It is of five different types with each type having different severity outcomes. For almost three decades, only supportive measures were advocated in the treatment of SMA. Recently, Biogen’s Spinraza came out as the first disease modifying therapy to treat infantile as well as adult SMA. This review throws light on the pharmacological aspects of the drug; its approval by Food and Drug Administration and various completed clinical trials as well ongoing clinical trials.

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Selecting disease‐modifying medications in 5q spinal muscular atrophy

Muscle & Nerve ◽

10.1002/mus.27358 ◽

2021 ◽

Author(s):

Michael S. Cartwright ◽

Suraj Upadhya

Keyword(s):

Spinal Muscular Atrophy ◽

Muscular Atrophy ◽

Disease Modifying

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Molecular Pathophysiology and Disease-Modifying Therapies for Spinal and Bulbar Muscular Atrophy

Archives of Neurology ◽

10.1001/archneurol.2011.2308 ◽

2012 ◽

Vol 69 (4) ◽

pp. 436 ◽

Cited By ~ 16

Author(s):

Haruhiko Banno

Keyword(s):

Muscular Atrophy ◽

Disease Modifying Therapies ◽

Disease Modifying ◽

Molecular Pathophysiology

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A Canadian Adult Spinal Muscular Atrophy Outcome Measures Toolkit: Results of a National Consensus using a Modified Delphi Method

Journal of Neuromuscular Diseases ◽

10.3233/jnd-200617 ◽

2021 ◽

pp. 1-10

Author(s):

Jeremy Slayter ◽

Victoria Hodgkinson ◽

Josh Lounsberry ◽

Bernard Brais ◽

Kristine Chapman ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Outcome Measures ◽

Delphi Method ◽

Muscular Atrophy ◽

Quality Data ◽

High Quality ◽

High Quality Data ◽

Modified Delphi Method ◽

Modified Delphi ◽

Disease Modifying

Background: Spinal Muscular Atrophy (SMA) is a rare disease that affects 1 in 11 000 live births. Recent developments in SMA treatments have included new disease-modifying therapies that require high quality data to inform decisions around initiation and continuation of therapy. In Canada, there are no nationally agreed upon outcome measures (OM) used in adult SMA. Standardization of OM is essential to obtain high quality data that is comparable among neuromuscular clinics. Objective: To develop a recommended toolkit and timing of OM for assessment of adults with SMA. Methods: A modified delphi method consisting of 2 virtual voting rounds followed by a virtual conference was utilized with a panel of expert clinicians treating adult SMA across Canada. Results: A consensus-derived toolkit of 8 OM was developed across three domains of function, with an additional 3 optional measures. Optimal assessment frequency is 12 months for most patients regardless of therapeutic access, while patients in their first year of receiving disease-modifying therapy should be assessed more frequently. Conclusions: The implementation of the consensus-derived OM toolkit will improve monitoring and assessment of adult SMA patients, and enrich the quality of real-world evidence. Regular updates to the toolkit must be considered as new evidence becomes available.

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Respiratory Issues in patients with Spinal Muscular Atrophy (SMA) type 1, Treated with Disease-Modifying Therapy

10.1183/13993003.congress-2021.pa3470 ◽

2021 ◽

Author(s):

Mirella Gaboli ◽

Mercedes López-Lobato ◽

Marcos Madruga-Garrido ◽

Macarena Borrero-Rodriguez ◽

Alejandro Palomo-Pavón ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Muscular Atrophy ◽

Disease Modifying Therapy ◽

Disease Modifying

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Spinal Muscular Atrophy: The Use of Functional Motor Scales in the Era of Disease-Modifying Treatment

Child Neurology Open ◽

10.1177/2329048x211008725 ◽

2021 ◽

Vol 8 ◽

pp. 2329048X2110087

Author(s):

Katarzyna Pierzchlewicz ◽

Izabela Kępa ◽

Jacek Podogrodzki ◽

Katarzyna Kotulska

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Function ◽

Muscular Atrophy ◽

Age Groups ◽

Ventilatory Support ◽

Gene Replacement ◽

Motor Disability ◽

Smn2 Gene ◽

Disease Modifying ◽

Smn Protein

Spinal muscular atrophy (SMA) is a genetic condition characterized by progressive motoneuron loss. Infants affected by SMA type 1 do not gain developmental milestones and acutely decline, requiring ventilatory support. Several scales are used to assess motor disability and its progression in SMA. Recently, 3 disease-modifying therapies have been approved for SMA patients: nusinersen, an intrathecal antisense oligonucleotide enhancing SMN protein production by the SMN2 gene, risdiplam, also influencing the SMN2 gene to stimulate SMN production but administered orally, and onasemnogene abeparvovec-xioi, an SMN1 gene replacement therapy. Thus, the functional scales should now be applicable for patients improving their motor function over time to assess treatment efficacy. In this paper, we compare different functional scales used in SMA patients. Their usefulness in different SMA types, age groups, and feasibility in daily clinical practice is described below. Some changes in motor function assessments in SMA are also suggested.

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