Migrating atelectasis in Werdnig-Hoffmann disease: Pulmonary manifestations in two cases of spinal muscular atrophy type 1

Leistikow, E.A.; Jones, Norman; Josephson, K.D.; Sierra, Teresa; Costakos, D.T.; Sprague, Daniel; Gorch, D.H.; Asonye, U.O.

doi:10.1002/(sici)1099-0496(199908)28:2<149::aid-ppul12>3.0.co;2-w

Cited by 7 publications

(2 citation statements)

References 4 publications

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“…In some patients, atelectasis is reported,38, 39 and structural lung damage is observed after autopsy. In severe SMA mice, lung abnormalities are also found 40 .…”

Section: Discussionmentioning

confidence: 99%

Efficient SMN Rescue following Subcutaneous Tricyclo-DNA Antisense Oligonucleotide Treatment

Robin

Griffith

Carter

et al. 2017

Molecular Therapy - Nucleic Acids

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Spinal muscular atrophy (SMA) is a recessive disease caused by mutations in the SMN1 gene, which encodes the protein survival motor neuron (SMN), whose absence dramatically affects the survival of motor neurons. In humans, the severity of the disease is lessened by the presence of a gene copy, SMN2. SMN2 differs from SMN1 by a C-to-T transition in exon 7, which modifies pre-mRNA splicing and prevents successful SMN synthesis. Splice-switching approaches using antisense oligonucleotides (AONs) have already been shown to correct this SMN2 gene transition, providing a therapeutic avenue for SMA. However, AON administration to the CNS presents additional hurdles. In this study, we show that systemic delivery of tricyclo-DNA (tcDNA) AONs in a type III SMA mouse augments retention of exon 7 in SMN2 mRNA both in peripheral organs and the CNS. Mild type III SMA mice were selected as opposed to the severe type I model in order to test tcDNA efficacy and their ability to enter the CNS after maturation of the blood brain barrier (BBB). Furthermore, subcutaneous treatment significantly improved the necrosis phenotype and respiratory function. In summary, our data support that tcDNA oligomers effectively cross the blood-brain barrier and offer a promising systemic alternative for treating SMA.

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“…In some patients, atelectasis is reported,38, 39 and structural lung damage is observed after autopsy. In severe SMA mice, lung abnormalities are also found 40 .…”

Section: Discussionmentioning

confidence: 99%

Efficient SMN Rescue following Subcutaneous Tricyclo-DNA Antisense Oligonucleotide Treatment

Robin

Griffith

Carter

et al. 2017

Molecular Therapy - Nucleic Acids

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“…In advanced neuromuscular disorders (NMDs), pneumonia and atelectasis are typical severe respiratory complications. 1,2 Incidence rates of one pneumonia per year were reported for Duchenne muscular dystrophy and other myopathies, but are likely to be higher in advanced disease. 3,4 A viral infection of the upper airways impairs already weak respiratory muscles.…”

Section: Introductionmentioning

confidence: 99%

IPPB-assisted coughing in neuromuscular disorders

Dohna-Schwake

Ragette²,

Teschler³

et al. 2006

Pediatr. Pulmonol.

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In neuromuscular disorders, reduced peak cough flows (PCFs) are considered to increase the risk of respiratory complications such as pneumonia or chronic atelectasis. Different methods were described to improve PCF. However, these studies were primarily carried out in adults, and there is limited information regarding the use and efficacy of these methods in children with respiratory muscle weakness. The aim of this study was to investigate whether hyperinsufflation with an intermittent positive-pressure breathing (IPPB) device is effective in cough augmentation in pediatric patients. Spirometry (forced inspiratory vital capacity, FIVC; forced expiratory volume in 1 sec, FEV1), respiratory muscle pressures (peak inspiratory pressure, PIP; peak expiratory pressure, PEP), and PCF were measured in 29 schoolchildren with various neuromuscular disorders. IPPB-assisted hyperinsufflation was taught individually to increase lung volumes (maximum insufflation capacity, MIC) above FIVC. The impact of hyperinsufflation on peak cough flow was documented. In 28/29 patients, IPPB-assisted hyperinsufflation enhanced FIVC from 0.68 +/- 0.40 l to an MIC of 1.05 +/- 0.47 l (P < 0.001). Unassisted PCF was 119.0 +/- 57.7 l/min, and increased to 194.5 +/- 74.9 l/min (P < 0.001) in 27/29 patients. This effect was similar in young patients (ages 6-10 years) and older patients (aged >10 years). Augmentation of lung volumes from FIVC to MIC correlated with an increase of PCF (R = 0.42, P < 0.05). IPPB-assisted hyperinsufflation improves PCF in pediatric neuromuscular disorders. The results suggest that this technique can be used to improve clearance of airway secretions and therefore reduce respiratory morbidity in children with NMD.

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W

Lachman

2007

Taybi and Lachman's Radiology of Syndromes, Metabolic Disorders and Skeletal Dysplasias

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Migrating atelectasis in Werdnig-Hoffmann disease: Pulmonary manifestations in two cases of spinal muscular atrophy type 1

Cited by 7 publications

References 4 publications

Efficient SMN Rescue following Subcutaneous Tricyclo-DNA Antisense Oligonucleotide Treatment

Efficient SMN Rescue following Subcutaneous Tricyclo-DNA Antisense Oligonucleotide Treatment

IPPB-assisted coughing in neuromuscular disorders

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