Impact of Disease Severity and Disease-Modifying Therapies on Myostatin Levels in SMA Patients

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8763 - 8763

Published: Aug. 12, 2024

Clinical trials with treatments inhibiting myostatin pathways to increase muscle mass are currently ongoing in spinal muscular atrophy. Given evidence of potential pathway downregulation Spinal Muscular Atrophy (SMA), restoring sufficient levels using disease-modifying (DMTs) might arguably be necessary prior considering inhibitors as an add-on treatment. This retrospective study assessed pre-treatment and follistatin levels’ correlation disease severity explored their alteration by treatment SMA. We retrospectively collected clinical characteristics, motor scores, mysotatin between 2018 2020 25 Belgian patients SMA (SMA1 (n = 13), SMA2 6), 3 6)) treated nusinersen. Data were after 2, 6, 10, 18, 30 months Myostatin correlated patients’ age, weight, type, function before initiation. After treatment, we observed correlations some scores (i.e., MFM32, HFMSE, 6MWT), but no major effect nusinersen on or over time. In conclusion, further research is needed determine if DMTs can impact SMA, how this could potentially influence patient selection for inhibitor trials.

Language: Английский

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Assessment of social emotional, cognitive and communicative development and adaptive behavior in children with spinal muscular atrophy 5q

Neuromuscular Diseases, Journal Year: 2025, Volume and Issue: 15(1), P. 39 - 52

Published: April 26, 2025

Background. Spinal muscular atrophy 5q (SMA) is a severe genetic neuromuscular disorder, which primarily manifested through musclar weakness. Previously, cognitive development in the natural course of SMA was considered normal. The introduction etiopathogenetic therapy has altered disease trajectory, led to new phenotypes, improved survival rates, and outlined importance studying emotional, cognitive, communicative domains, adaptive behavior patients. Aim. To conduct comprehensive assessment as well speech development, patients with genetically confirmed SMA, including cases, were identified newborn screening programs asymptomatic at initiation therapy, identify factors influencing neuropsychic Materials methods. study included 87 receiving aged 0–12 years (median age testing – 57.0 [37.0; 103.0] months). Developmental Profile-3 (DP-3) instrument used assess development. Statistical analysis performed using SPSS Statistics v.26.0 (IBM, USA). Results. Children who received presymptomatic stage (6.9 % cohort) showed no deficits any assessed developmental domains. These results significantly differed from those types 1, 2, 3 motor skills (padj <0.001) ≤0.026). Patients exhibited impairments (reduced 93.0 %, 89.7 88.9 children, respectively) (impairments ≥55 each group). type 1 additionally demonstrated delays social emotional (39.5 %), (30.2 %) lower functional status (“lying”) had more pronounced adaptive, domains (p ≤0.048). In fewer SMN2 gene copies earlier onset correlated (SMN2 copies: p ≤0.034; onset: ≤0.012). dysphagia scores across all subscales except ≤0.015). Chronic respiratory insufficiency associated reduced five subscales: skills, affected ≤0.045); ≤0.018). Delayed ≤0.012), 2 ≤0.002), ≤0.048), worse outcomes = 0.001). Conclusion. exhibit not only but also socialization deficits, A standardized approach identifying these should be developed, developing tailored rehabilitation methods important well. Initiating may prevent neuropsychiatric manifestations SMA.

Language: Английский

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Intra-amniotic antisense oligonucleotide treatment improves phenotypes in preclinical models of spinal muscular atrophy

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(798)

Published: May 14, 2025

Neurological disorders with onset before or at birth are a leading cause of morbidity and mortality in infants children. Prenatal treatment has the potential to reduce prevent irreversible neuronal loss facilitate normal neurodevelopment. We hypothesized that antisense oligonucleotides (ASOs) delivered amniotic fluid by intra-amniotic (IA) injection could safely distribute fetal central nervous system (CNS) provide therapeutic benefit motor neuron disease spinal muscular atrophy (SMA), caused mutations survival 1 gene ( SMN1 ), deficiency SMN protein. Although splice-switching ASO nusinersen ameliorates SMA when postnatally, substantial deficits can remain severely affected infants. Here, IA ASOs into two mouse models severe increased expression CNS. In SMAΔ7 mice, which manifest pathology utero, prenatal improved numbers, axon development, behavioral tests, compared those mice treated postnatally (between P1 P3). To assess feasibility large-animal model, were midgestation sheep intracranial injection. distributed cord concentrations multiple peripheral tissues without evidence toxicity fetus mother. These data demonstrated delivery holds as minimally invasive approach for possibly other severe, early-onset neurological disorders.

Language: Английский

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Treatment Guidelines and Rehabilitation in Spinal Muscular Atrophy and Duchenne’s Muscular Dystrophy

Physical Medicine and Rehabilitation Clinics of North America, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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Trio-whole exome sequencing reveals the importance of de novo variants in children with intellectual disability and developmental delay

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 11, 2024

Understanding the genetic basis of developmental delay (DD) and intellectual disability (ID) remains a considerable clinical challenge. This study evaluated application trio whole exome sequencing (WES) in children diagnosed with DD/ID. The comprised 173 unexplained participants underwent trio-WES their demographic, clinical, characteristics were evaluated. Based on features, classified into two groups for further analysis: syndromic DD/ID group non-syndromic group. diagnostic yield was 49.7% (86/173). included 58 pathogenic or likely single nucleotide variants (SNVs) 41 genes identified across 54 individuals (31.2%) through trio-WES. Among these, 22 SNVs had not been previously reported. Additionally, 30 copy number variations (CNVs) detected 36 (20.8%). higher than that (57.8% vs. 47.2%, P < 0.001). Within subgroup, epilepsy subgroup (83.9%) significantly those other subgroups (P analysis individuals' phenotypes, facial dysmorphism shown (68.2%, accompanied by epilepsy, whereas CNVs without Similarly, de novo group, while (all Trio-WES is crucial tool diagnosis DD/ID, demonstrating up to 49.7%. De autosomal dominant are significant contributors particularly non-consanguineous families.

Language: Английский

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Treatment of spinal muscular atrophy

Current Opinion in Pediatrics, Journal Year: 2024, Volume and Issue: 36(6), P. 612 - 618

Published: Sept. 13, 2024

The aim of the review was to provide an overview safety and efficacy available treatments including information from both clinical trials real-world data. Additional form ongoing studies using other approaches than increasing SMN protein are also reported.

Language: Английский

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Cognitive impairment in children with 5q-associated spinal muscular atrophy type 1: two case reports and the review of the literature

Frontiers in Pediatrics, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 27, 2024

Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by mutations in the survival motor neuron 1 (SMN1) gene on chromosome 5, leading to degeneration of lower neurons. There are few studies cognitive impairment comorbid with SMA. Here, we report two cases severe Chinese children SMA type 1, marking first such reports this demographic. We propose that dysfunction may be a comorbidity Clinicians should consider patients presenting muscle weakness and accompanied impairments, avoid misdiagnosis oversight.

Language: Английский

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Home mechanical ventilation in children: evolving indications in an era of new treatment options

European Respiratory Review, Journal Year: 2024, Volume and Issue: 33(174), P. 240154 - 240154

Published: Oct. 1, 2024

Worldwide, there has been a dramatic increase in the use of paediatric home mechanical ventilation (HMV). In this review, we examine rapid evolution clinical practice through prism two distinct groups children: those with neurodisability/medical complexity and patients neuromuscular disease. We illustrate changes service provision for these that are driven by recognition early intervention HMV can enhance quality life children may complement beneficial effects novel disease-modifying medications to improve survival. Alongside this, highlight importance balancing patient expectations need discuss ethical challenges be encountered when delivering increasing population children.

Language: Английский

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