Respiratory outcomes of onasemnogene abeparvovec treatment for spinal muscular atrophy: national real-world cohort study.

Onasemnogene abeparvovec (OA) is a novel gene replacement therapy for patients with spinal muscular atrophy (SMA). This study provides real-world respiratory data for pediatric SMA patients receiving OA who were assessed before and one year after treatment in a multicenter cohort study conducted from 2019 to 2021. Twenty-five OA-treated SMA patients (23 with type 1 and 2 with type 2; median age at treatment 6.

Treating late-onset Tay Sachs disease: Brain delivery with a dual trojan horse protein.

Tay-Sachs (TS) disease is a neurodegenerative disease resulting from mutations in the gene encoding the α-subunit (HEXA) of lysosomal β-hexosaminidase A (HexA). We report that (1) recombinant HEXA alone increased HexA activity and decreased GM2 content in human TS glial cells and peripheral mononuclear blood cells; 2) a recombinant chimeric protein composed of HEXA linked to two blood-brain barrier (BBB) entry elements, a transferrin receptor binding sequence and granulocyte-colony stimulating factor, associates with HEXB ; reaches human cultured TS cells lysosomes and mouse brain cells, especially neurons, ; lowers GM2 in cultured human TS cells; lowers whole brain GM2 concentration by approximately 40% within 6 weeks, when injected intravenously (IV) to adult TS-mutant mice mimicking the slow course of late-onset TS; and increases forelimbs grip strength. Hence, a chimeric protein equipped with dual BBB entry elements can transport a large protein such as HEXA to the brain, decrease the accumulation of GM2, and improve muscle strength, thereby providing potential treatment for late-onset TS.

Non-ionizing measurement and quantification of bell-shaped chests in spinal muscular atrophy: a pilot study.

Background: Spinal Muscular Atrophy (SMA) is manifested by deformation of the chest wall, including a bell-shaped chest. We determined the ability of a novel non-ionizing, non-volitional method to measure and quantify bell-shaped chests in SMA.

Methods: A 3D depth camera and a chest x-ray (CXR) were used to capture chest images in 14 SMA patients and 28 controls.

Real-Life Outcome After Gene Replacement Therapy for Spinal Muscular Atrophy: A Multicenter Experience.

Background: Onasemnogene abeparvovec-xioi (OA) has been available since 2019 as a gene replacement therapy for individuals with spinal muscular atrophy (SMA) under age two years. We aim to expand upon the sparse knowledge about its safety and clinical efficacy.

Methods: The clinical outcome data of all the individuals with SMA who were treated with gene therapy in four tertiary hospitals in Israel were retrieved and analyzed.

Cerebrospinal fluid characteristics of patients treated with intrathecal nusinersen for spinal muscular atrophy.

Introduction/aims: There is limited information on the potential effects of repeated intrathecal antisense oligonucleotide drug delivery on cerebrospinal fluid (CSF) biochemical and blood cell profiles. This study aimed to examine longitudinal changes in the biochemical components (glucose, protein) and blood cell counts in the CSF of spinal muscular atrophy (SMA) patients treated with intrathecal nusinersen.

Methods: We collected and analyzed clinical and CSF parameters (cell count, protein, glucose, culture) of 50 individuals with SMA during nusinersen treatment (22 type 1, 17 type 2, and 11 type 3).

Muscle microRNAs in the cerebrospinal fluid predict clinical response to nusinersen therapy in type II and type III spinal muscular atrophy patients.

Background And Purpose: The antisense oligonucleotide nusinersen (Spinraza) regulates splicing of the survival motor neuron 2 (SMN2) messenger RNA to increase SMN protein expression. Nusinersen has improved ventilator-free survival and motor function outcomes in infantile onset forms of spinal muscular atrophy (SMA), treated early in the course of the disease. However, the response in later onset forms of SMA is highly variable and dependent on symptom severity and disease duration at treatment initiation.

Adeno-associated virus serotype 9 antibody titers in patients with SMA pre-screened for treatment with onasemnogene abeparvovec -routine care evidence.

Spinal muscular atrophy (SMA) is characterized by progressive weakness of skeletal and respiratory muscles. This study aimed to evaluate the prevalence of pre-existing anti adeno-associated virus serotype 9 antibody (AAV9-Ab) titers among infantile-onset SMA diagnosed infants pre-screened for treatment with AAV9-based onasemnogene abeparvovec, and to explore whether clinical and/or demographic characteristics are correlated with AAV9 Ab test results. This is a retrospective multicenter study of children diagnosed with 5q SMA younger than two years of age.

Nonrespiratory complications of nusinersen-treated spinal muscular atrophy type 1 patients.

Background: Emergence of new treatments for spinal muscular atrophy type 1 (SMA1) has led to dramatic improvements in respiratory failure and survival. However, these "treated" patients sustain major problems in other organ systems, which may directly or indirectly affect their respiratory function. We observed three main nonrespiratory manifestations in these patients comprised of facial deformities, feeding problems, and spinal deformities.

Diagnostic yield of chromosomal microarray and trio whole exome sequencing in cryptogenic cerebral palsy.

Objective: To determine the yield of genetic diagnoses using chromosomal microarray (CMA) and trio whole exome sequencing (WES), separately and combined, among patients with cryptogenic cerebral palsy (CP).

Methods: Trio WES of patients with prior CMA analysis for cryptogenic CP, defined as disabling, non-progressive motor symptoms beginning before the age of 3 years without known cause.

Results: Given both CMA analysis and trio WES, clinically significant genetic findings were identified for 58% of patients (26 of 45).

Variable Genotype-Phenotype Correlation of Pompe's Disease Caused by a c.2015 G > A (p.Arg672Gln) Mutation in the GAA Gene.

Pompe's disease occurs due to an autosomal recessive trait resulting from numerous distinctive mutations in the gene. It manifests as a broad spectrum of clinical phenotypes with progressive weakness that impairs motor and respiratory functions being common for all its forms. Cardiac hypertrophy is a prominent feature of its classic infantile form.

Nutritional Therapy in Children With Spinal Muscular Atrophy in the Era of Nusinersen.

Objectives: Spinal muscular atrophy (SMA) is a genetic motor neuron disorder characterized by progressive muscle atrophy. Our aims were to evaluate the impact of nutritional intervention and nusinersen therapy on the nutritional status of SMA patients.

Study Design: This prospective study included all children and young adults (<24 years of age) with SMA who attended our multidisciplinary SMA clinic, during January 2017-July 2019.

Nusinersen for spinal muscular atrophy type 1: Real-world respiratory experience.

Background: The emergence of new treatments for spinal muscular atrophy (SMA) is revolutionary, especially for SMA type 1 (SMA1). Data on respiratory outcomes remain sparse and rely mostly on randomized clinical trials. We report our experience of Nusinersen-treated SMA1 patients in real-world settings.

The endocrine manifestations of spinal muscular atrophy, a real-life observational study.

The introduction of nusinersen, the first therapeutic modality for Spinal Muscular Atrophy (SMA) patients has raised hopes and led to construction of a multi-professional medical SMA service, including pediatric endocrinology. Our study aimed to provide a comprehensive description of the endocrine manifestations of SMA patients with variable degree of sarcopenia. Real-life clinical and laboratory data of 62 SMA patients (age range 3 months to 31 years, 24 type 1, 21 type 2, 17 type 3) were collected including: weight-status, self-reported information on puberty, current pubertal stage, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), basal gonadotropin and androgen levels.

Prediction of Drug-Resistant Epilepsy in Children With Cerebral Palsy.

Epilepsy is estimated to exist in approximately 40% of individuals with cerebral palsy; however, the specific features that make it drug resistant are not well defined. The main aim of this study was to determine the clinical risk factors that could predict drug-resistant epilepsy, in children with cerebral palsy. The study was performed via a retrospective chart review, analyzing clinical parameters of 118 children with cerebral palsy with either drug-resistant epilepsy or controlled epilepsy, between the years 2013 and 2018.

Treatment of electrical status epilepticus in sleep: A pooled analysis of 575 cases.

Objective: Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is a pediatric epilepsy syndrome with sleep-induced epileptic discharges and acquired impairment of cognition or behavior. Treatment of ESES is assumed to improve cognitive outcome. The aim of this study is to create an overview of the current evidence for different treatment regimens in children with ESES syndrome.

Botulinum toxin a injections to the upper limbs in children with cerebral palsy: duration of effect.

We report our experience on the duration of effectiveness of botulinum toxin A injections to the upper extremities of children with cerebral palsy. A retrospective chart review was conducted on 30 consecutive patients (mean age, 9.9 ± 5.

Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES).

Purposes: To describe the clinical spectrum and to evaluate the efficacy of different therapeutic agents in children with electrical status epilepticus in sleep (ESES).

Methods: Clinical data of all patients with ESES (not including patients with Landau-Kleffner syndrome) in four pediatric neurology outpatient clinics were analyzed. Thirty patients with ESES had been treated between 1994 and 2007.

Clinical significance of the parental origin of the X chromosome in turner syndrome.

Context: The phenotype in Turner syndrome (TS) is variable, even in patients with a supposedly nonmosaic karyotype. Previous work suggested that there were X-linked parent-of-origin effects on the phenotype.

Hypothesis: The TS phenotype is influenced by the parental origin of the missed X chromosome.