8,707 results match your criteria Spinal Muscular Atrophy


Fatigue in adults with spinal muscular atrophy under treatment with nusinersen.

Sci Rep 2020 Jul 6;10(1):11069. Epub 2020 Jul 6.

Department of Neurology, University Hospital Essen, Essen, Germany.

5q-Associated spinal muscular atrophy is a hereditary neuromuscular disease leading to progressive muscle weakness in which fatigue occurs and affects quality of life. Treatment with the antisense oligonucleotide nusinersen has been shown to improve motor function. Fatigue can be measured within the Fatigue Severity Scale (FSS). Read More

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http://dx.doi.org/10.1038/s41598-020-68051-wDOI Listing

Metabolic alterations in spinal and bulbar muscular atrophy.

Rev Neurol (Paris) 2020 Jul 3. Epub 2020 Jul 3.

Department of Neurosciences, University of Padova, via Giustiniani 1, 35128 Padova, Italy. Electronic address:

Spinal and bulbar muscular atrophy (SBMA) is a rare, X-linked neuromuscular disease characterised by lower motor neurons degeneration, slowly progressive myopathy and multisystem involvement. SBMA is caused by trinucleotide repeat expansion in the first exon of the androgen receptor (AR) gene on chromosome X that encodes a polyglutamine (polyQ) tract in the AR protein. Disease onset occurs between 30-60 years of age with easy fatigability, muscle cramps, and weakness in the limbs. Read More

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http://dx.doi.org/10.1016/j.neurol.2020.03.020DOI Listing

Spinal muscular atrophy and Farber disease due to ASAH1 variants: A case report.

Am J Med Genet A 2020 Jul 5. Epub 2020 Jul 5.

Department of Neurology, University of Rochester, Rochester, New York, USA.

Genetic variations in the ASAH1 gene are associated with a spectrum of disorders ranging from Farber disease (FD) to spinal muscular atrophy with or without progressive myoclonic epilepsy (SMA-PME). FD presents most commonly in infants with subcutaneous joint nodules, progressive arthritis and granulomas of the larynx and epiglottis leading to a hoarse cry. SMA-PME is characterized by childhood onset progressive weakness due to motor neuron disease followed by progressive epilepsy, tremor, and sensorineural hearing loss. Read More

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http://dx.doi.org/10.1002/ajmg.a.61764DOI Listing

Anesthetic Management of Pediatric Patients Undergoing Intrathecal Nusinersen Administration for Treatment of Spinal Muscular Atrophy: A Single Center Experience.

Paediatr Anaesth 2020 Jul 4. Epub 2020 Jul 4.

Department of Anesthesia, McGovern Medical School, Houston, United States of America.

Background: Spinal muscular atrophy are a group of autosomal recessive inherited neurological disorders secondary to a genetic mutation that leads to progressive muscle weakness and atrophy. Recently approved by the Food and Drug Administration, Nusinersen is the first treatment specifically for spinal muscular atrophy. This drug must be administered intrathecally, as it does not cross the blood brain barrier. Read More

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http://dx.doi.org/10.1111/pan.13964DOI Listing

Does physical exercise training improve functional performance in type 3 spinal muscular atrophy? A Cochrane Review summary with commentary.

Dev Med Child Neurol 2020 Jul 4. Epub 2020 Jul 4.

Faculty of Rehabilitation and Allied Health Sciences, Riphah International University, Islamabad, Pakistan.

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http://dx.doi.org/10.1111/dmcn.14622DOI Listing

Neurogenic calf amyotrophy with CK elevation by entrapment radiculopathy; clinical, radiological, and pathological analyses of 18 cases.

J Neurol 2020 Jul 3. Epub 2020 Jul 3.

Department of Neurology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

Objective: To characterize the clinical, radiological, and pathological manifestations of 18 cases showing neurogenic calf amyotrophy with creatine kinase (CK) elevation by entrapment radiculopathy (NCACKEER).

Methods: We retrospectively reviewed and evaluated the medical records of patients who complained of weakness or atrophy of the calf muscles in our department between 2004 and 2019. We identified 18 cases fulfilling the proposed criteria of NCACKEER. Read More

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http://dx.doi.org/10.1007/s00415-020-10021-3DOI Listing

Autophagy in motor neuron diseases.

Prog Mol Biol Transl Sci 2020 24;172:157-202. Epub 2020 Apr 24.

Deutsche Zentrum für Neurodegenerative Erkrankungen e.V, DZNE/German Center for Neurodegenerative Diseases, Dresden, Germany; Technische Universität Dresden, CRTD/Center for Regenerative Therapies Dresden, Dresden, Germany; Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany. Electronic address:

Motor neuron diseases (MNDs) are a wide group of neurodegenerative disorders characterized by the degeneration of a specific neuronal type located in the central nervous system, the motor neuron (MN). There are two main types of MNs, spinal and cortical MNs and depending on the type of MND, one or both types are affected. Cortical MNs innervate spinal MNs and these control a variety of cellular targets, being skeletal muscle their main one which is also affected in MNDs. Read More

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http://dx.doi.org/10.1016/bs.pmbts.2020.03.009DOI Listing

SOD1 mutations in adult-onset distal spinal muscular atrophy.

Eur J Neurol 2020 Jul 3. Epub 2020 Jul 3.

Neuromuscular Unit, Department of Neurology, 12 de Octubre University Hospital, Madrid, Spain.

We read with interest the paper "SOD1 p.D12Y variant is associated with ALS/distal myopathy spectrum", recently published by Tasca et al., where four patients heterozygous for the p. Read More

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http://dx.doi.org/10.1111/ene.14426DOI Listing

Response to: SOD1 mutations in adult-onset distal spinal muscular atrophy.

Eur J Neurol 2020 Jul 2. Epub 2020 Jul 2.

Unità Operativa Complessa di Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia.

We thank Dr de Fuenmayor-Fernández de la Hoz and colleagues for their interest in our paper and their comments. Clearly distinguishing neurogenic from myogenic disease processes is not always straightforward and we fully share the view that, to some extent, myopathic alterations on muscle biopsy may come along with long-standing denervation, thus configuring a so-called "secondary myopathy". This could in fact be the major contributing factor to explain the imaging and pathology features of patient 4 in our paper. Read More

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http://dx.doi.org/10.1111/ene.14425DOI Listing

Nusinersen ameliorates motor function and prevents motoneuron Cajal body disassembly and abnormal poly(A) RNA distribution in a SMA mouse model.

Sci Rep 2020 Jul 1;10(1):10738. Epub 2020 Jul 1.

"Instituto de Investigación Marqués de Valdecilla" (IDIVAL), Santander, Spain.

Spinal muscular atrophy (SMA) is a devastating autosomal recessive neuromuscular disease characterized by degeneration of spinal cord alpha motor neurons (αMNs). SMA is caused by the homozygous deletion or mutation of the survival motor neuron 1 (SMN1) gene, resulting in reduced expression of SMN protein, which leads to αMN degeneration and muscle atrophy. The majority of transcripts of a second gene (SMN2) generate an alternative spliced isoform that lacks exon 7 and produces a truncated nonfunctional form of SMN. Read More

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http://dx.doi.org/10.1038/s41598-020-67569-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330045PMC

Commentary on "Stander Use in Spinal Muscular Atrophy: Results From a Large Natural History Database".

Pediatr Phys Ther 2020 Jul;32(3):242

Columbia University Irving Medical Center New York City, New York.

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http://dx.doi.org/10.1097/PEP.0000000000000722DOI Listing

Survival motor neuron protein protects H9c2 cardiomyocytes from hypoxia-induced cell injury by reducing apoptosis.

Clin Exp Pharmacol Physiol 2020 Jun 30. Epub 2020 Jun 30.

Department of Cardiovascular Center, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.

Background: Hypoxia induces cell injury in cardiomyocytes and leads to the development of cardiovascular diseases. The survival motor neuron protein (SMN) is a crucial ubiquitous protein whose functional deficiency causes motor neuron loss seen in spinal muscular atrophy. SMN has shown protective effects on the cardiovascular system and the aim of the present study was to investigate the cardioprotective effects of SMN on hypoxia-induced cell injury. Read More

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http://dx.doi.org/10.1111/1440-1681.13369DOI Listing

Correspondence on: "Discrepancy in Spinal Muscular Atrophy Incidence findings in newborn screening programs: the influence of carrier screening?" by Kay et al.

Genet Med 2020 Jun 30. Epub 2020 Jun 30.

Division of Child Neurology, Centre de Références des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liège & University of Liège, Liège, Belgium.

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http://dx.doi.org/10.1038/s41436-020-0887-1DOI Listing

Patient and family social media use surrounding a novel treatment for a rare genetic disease: a qualitative interview study.

Genet Med 2020 Jun 30. Epub 2020 Jun 30.

Stanford Center for Biomedical Ethics, Department of Medicine, Stanford University, Stanford, CA, USA.

Purpose: Advances in gene therapy and precision medicine have led to a growing number of novel treatments for rare genetic diseases. Patients/families may lack access to up-to-date, accurate, and relevant information about these treatments. Social media offers one potentially important resource for these communities. Read More

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http://dx.doi.org/10.1038/s41436-020-0890-6DOI Listing

Clinical features and long-term outcomes of pediatric spinal cord cavernous malformation-a report of 18 cases and literature review.

Childs Nerv Syst 2020 Jun 26. Epub 2020 Jun 26.

Medical School of Nankai University, No. 94, Weijin Road, Naikai District, Tianjin, 300071, People's Republic of China.

Purpose: Pediatric intramedullary spinal cord cavernous malformation (ISCM) is a rare vascular disease with unclear natural history and long-term outcomes. We aim to determine the demographics, hemorrhagic risk, and long-term outcomes of this rare entity.

Methods: A retrospective review of clinical data and treatment outcomes of pediatric patients treated with ISCM in our institution from 3/2000 to 3/2017 was conducted. Read More

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http://dx.doi.org/10.1007/s00381-020-04700-9DOI Listing

Gene therapeutic strategies and relevant clinical trials in neuromuscular disorder in China.

Gene Ther 2020 Jun 26. Epub 2020 Jun 26.

Neurology Department, Children's Hospital of Fudan University, NO.399 Wanyuan Road, Shanghai, China.

Neuromuscular disorder is a diverse group of genetic disease, among which Duchenne muscular dystrophy and Spinal muscular atrophy are most common. Recently, the great breakthroughs of gene targeted therapeutic strategies are leading a profound revolution in the standard care of neuromuscular disorders over the world including China. This review will offer an outline of the molecular pathogenesis, clinical progress, critical trials, as well as the challenges of new gene therapy in the treatment of Spinal muscular atrophy and Duchenne muscular dystrophy in China, mainly includes mRNA splicing modulators and adeno-associated virus mediated gene replacement. Read More

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http://dx.doi.org/10.1038/s41434-020-0158-4DOI Listing

Renal pathology in a mouse model of severe Spinal Muscular Atrophy is associated with downregulation of Glial Cell-Line Derived Neurotrophic Factor (GDNF).

Hum Mol Genet 2020 Jun 26. Epub 2020 Jun 26.

Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK.

Spinal Muscular Atrophy (SMA) occurs as a result of cell-ubiquitous depletion of the essential SMN protein. Characteristic disease pathology is driven by a particular vulnerability of the ventral motor neurons of the spinal cord to decreased SMN. Perhaps not surprisingly, many other organ systems are also impacted by SMN depletion. Read More

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http://dx.doi.org/10.1093/hmg/ddaa126DOI Listing

Efficacy of Botulinum Toxin for Treating Sialorrhea in Neuromuscular Conditions.

Front Neurol 2020 10;11:513. Epub 2020 Jun 10.

Assistant Professor of Neurology, Department of Neurology, University of Missouri, Columbia, MO, United States.

Drooling related to bulbar weakness and dysfunction is a common concern in patients with neuromuscular disease. While there are numerous medications to manage sialorrhea, they are often limited by side effects and lack of efficacy. Botulinum toxin has shown to benefit ALS patients in a few studies, but there is scant data on the benefit in other neuromuscular conditions. Read More

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http://dx.doi.org/10.3389/fneur.2020.00513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297943PMC

Calpain system is altered in survival motor neuron-reduced cells from in vitro and in vivo spinal muscular atrophy models.

Cell Death Dis 2020 Jun 25;11(6):487. Epub 2020 Jun 25.

Neuronal Signaling Unit, Experimental Medicine Department, Universitat de Lleida-IRBLleida, Rovira Roure, 80, Lleida, 25198, Spain.

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by loss of the survival motor neuron 1 (SMN1) gene. SMA is characterized by the degeneration of spinal cord motoneurons (MNs), progressive skeletal muscle atrophy, and weakness. The cellular and molecular mechanisms causing MN loss of function are only partially known. Read More

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http://dx.doi.org/10.1038/s41419-020-2688-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316821PMC

Relative hyperventilation in non-ventilated patients with spinal muscular atrophy.

Eur Respir J 2020 Jun 25. Epub 2020 Jun 25.

Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.

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http://dx.doi.org/10.1183/13993003.00162-2020DOI Listing

Generating ventral spinal organoids from human induced pluripotent stem cells.

Methods Cell Biol 2020 21;159:257-277. Epub 2020 Apr 21.

Institute of Molecular and Cell Biology, A*STAR Research Entities, Singapore; Yong Loo Lin School of Medicine (Physiology), National University of Singapore, Singapore; The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; National Neuroscience Institute, Singapore. Electronic address:

Current advances in human pluripotent stem cell (hPSC) technology allow directed differentiation into three-dimensional spinal organoid cultures that mimic the unique microenvironment and cytoarchitecture of the human spinal cord. Organoids also serves as important cellular tools to model spinal cord development and motor neuron diseases such as Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis. In this chapter, we describe a detailed step-by-step methodology to generate spinal organoids from human PSCs. Read More

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http://dx.doi.org/10.1016/bs.mcb.2020.03.010DOI Listing

Wide range of reduced penetrance alleles in spinal and bulbar muscular atrophy: a model-based approach.

J Med Genet 2020 Jun 22. Epub 2020 Jun 22.

Neurogenetics Unit, 1st Department of Neurology, National and Kapodistrian University of Athens, Eginition University Hospital, Athens, Greece

Background: Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is an X-linked motor neuron disorder caused by an expanded CAG repeat in the gene coding for the androgen receptor (AR). The range and significance of reduced penetrance alleles in SBMA has not been fully determined to date. We presently sought to determine the range of reduced penetrance alleles in SBMA. Read More

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http://dx.doi.org/10.1136/jmedgenet-2020-106963DOI Listing

Stander Use in Spinal Muscular Atrophy: Results From a Large Natural History Database.

Pediatr Phys Ther 2020 Jul;32(3):235-241

Department of Physical Therapy (Dr Townsend), School of Health and Rehabilitation Sciences, MGH Institute of Health Professions, Boston, Massachusetts; Center for Genomic Medicine and Department of Neurology (Drs Townsend, Simeone, and Swoboda and Mr Zhang), Massachusetts General Hospital, Boston, Massachusetts; Department of Physical Therapy and Human Movement Sciences and Department of Pediatrics (Dr Krosschell), Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Purpose: The purpose of this study was to describe stander use in a natural history cohort of drug therapy-naïve children with spinal muscular atrophy (SMA) who are not walking and identify factors associated with consistent stander use.

Methods: Data from 397 children with SMA types 1 and 2 characterized the prevalence and frequency of stander use. Predictors of consistent stander use explored were SMA type, survival motor neuron 2 gene (SMN2) copy number, respiratory support, and motor performance. Read More

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http://dx.doi.org/10.1097/PEP.0000000000000713DOI Listing

ACKNOWLEDGING LIMITS: STATISTICS AND THE CHILD'S QUALITY OF LIFE IN SPINAL MUSCULAR ATROPHY.

J Paediatr Child Health 2020 Jun;56(6):995-996

Paediatric Palliative Care, Pain Service,Department of Women's and Children's Health, University of Padua, Padua, Italy.

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http://dx.doi.org/10.1111/jpc.14959DOI Listing

Non-invasive assessment of motor unit activation in relation to motor neuron level and lesion location in stroke and spinal muscular atrophy.

Clin Biomech (Bristol, Avon) 2020 May 27;78:105053. Epub 2020 May 27.

Department of Rehabilitation and Prevention Engineering, Institute of Applied Medical Engineering, RWTH Aachen University, 52074 Aachen, Germany.

Background: Neuromuscular disorders e.g. spinal muscular atrophy and stroke have a negative impact on functional movement capability. Read More

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http://dx.doi.org/10.1016/j.clinbiomech.2020.105053DOI Listing

Whole-blood dysregulation of actin-cytoskeleton pathway in adult spinal muscular atrophy patients.

Ann Clin Transl Neurol 2020 Jun 17. Epub 2020 Jun 17.

Department of Neurology, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.

Objective: Recent advances in therapeutics have improved prognosis for severely affected spinal muscular atrophy (SMA) type 1 and 2 patients, while the best method of treatment for SMA type 3 patients with later onset of disease is unknown. To better characterize the SMA type 3 population and provide potential therapeutic targets, we aimed to understand gene expression differences in whole blood of SMA type 3 patients (n = 31) and age- and gender-matched controls (n = 34).

Methods: We performed the first large-scale whole blood transcriptomic screen with L1000, a rapid, high-throughput gene expression profiling technology that uses 978 landmark genes to capture a representation of the transcriptome and predict expression of 9196 additional genes. Read More

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http://dx.doi.org/10.1002/acn3.51092DOI Listing

Clinical service delivery of non-invasive prenatal diagnosis (NIPD) by relative haplotype dosage (RHDO) for single gene disorders.

J Mol Diagn 2020 Jun 15. Epub 2020 Jun 15.

West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Edgbaston, B15 2TG.

We have developed and implemented into routine clinical practice a relative haplotype dosage (RHDO) based method for non-invasive prenatal diagnosis (NIPD) of multiple single gene disorders: spinal muscular atrophy (SMA), Duchenne and Becker muscular dystrophies (DMD/BMD) and cystic fibrosis (CF). This review describes our experience of the first 152 pregnancies to have NIPD by RHDO as part of a routine clinical service. We have demonstrated that it is possible to provide a result within a clinically useful timeframe (mean 11 calendar days) with a very low failure rate (4%), none being due to a technical failure. Read More

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http://dx.doi.org/10.1016/j.jmoldx.2020.06.001DOI Listing
June 2020
4.851 Impact Factor

Characteristics of circular RNAs generated by human Survival Motor Neuron genes.

Cell Signal 2020 Jun 15;73:109696. Epub 2020 Jun 15.

Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States of America. Electronic address:

Circular RNAs (circRNAs) belong to a diverse class of stable RNAs expressed in all cell types. Their proposed functions include sponging of microRNAs (miRNAs), sequestration and trafficking of proteins, assembly of multimeric complexes, production of peptides, and regulation of transcription. Backsplicing due to RNA structures formed by an exceptionally high number of Alu repeats lead to the production of a vast repertoire of circRNAs by human Survival Motor Neuron genes, SMN1 and SMN2, that code for SMN, an essential multifunctional protein. Read More

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http://dx.doi.org/10.1016/j.cellsig.2020.109696DOI Listing
June 2020
4.315 Impact Factor

Mutation analysis of 419 family and prenatal diagnosis of 339 cases of spinal muscular atrophy in China.

BMC Med Genet 2020 Jun 18;21(1):133. Epub 2020 Jun 18.

The Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Add: No. 1, Jianshe East Rd, Erqi District, Zhengzhou, Henan Province, China.

Background: Spinal muscular atrophy (SMA) is a common and lethal autosomal recessive neurodegenerative disease caused by mutations in the survival motor neuron 1 (SMN1) gene. At present, gene therapy medicine for SMA, i.e. Read More

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http://dx.doi.org/10.1186/s12881-020-01069-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302341PMC

[Molecular therapies in childhood neuromuscular disorders-definite hope versus unknown pitfalls].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Jul;63(7):891-897

Abteilung Pädiatrische Neurologie, Universitätskinderklinik, Universitätsklinikum Essen, Essen, Deutschland.

Spinal muscular atrophy and muscular dystrophy Duchenne belong to the group of rare neuromuscular diseases manifesting in early childhood. Therapeutic options for some of these rare monogenic diseases have changed significantly in recent years. Molecular therapies such as direct gene transfer or alternative processing of the disease-specific gene play an important role in this transformation. Read More

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http://dx.doi.org/10.1007/s00103-020-03165-0DOI Listing

Measuring Outcomes in Adults with Spinal Muscular Atrophy - Challenges and Future Directions - Meeting Report.

J Neuromuscul Dis 2020 Jun 12. Epub 2020 Jun 12.

Department of Neurology, University of Essen, Essen, Germany.

Spinal muscular atrophy (SMA) is a progressive autosomal recessive motor neuron disease which affects 1 in 6,000-10,000 live births, caused by loss of the survival motor neuron 1 gene (SMN1). A major focus of therapeutic developments has been on increasing the full-length SMN protein by increasing the inclusion of exon 7 in SMN2 transcripts, enhancing SMN2 gene expression, stabilizing the SMN protein or replacing the SMN1 gene.In June 2017, FDA and EMA have approved the antisense oligonucleotide Nusinersen as the first treatment for all SMA subtypes without age restriction. Read More

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http://dx.doi.org/10.3233/JND-200534DOI Listing

RNA in spinal muscular atrophy: therapeutic implications of targeting.

Expert Opin Ther Targets 2020 Jun 25:1-13. Epub 2020 Jun 25.

Department of Biomedical Sciences, Iowa State University , Ames, IA, USA.

Introduction: Spinal muscular atrophy (SMA) is caused by low levels of the Survival Motor Neuron (SMN) protein due to deletions of or mutations in the gene. Humans carry another nearly identical gene, , which mostly produces a truncated and less stable protein SMNΔ7 due to predominant skipping of exon 7. Elevation of SMN upon correction of exon 7 splicing and gene therapy have been proven to be the effective treatment strategies for SMA. Read More

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http://dx.doi.org/10.1080/14728222.2020.1783241DOI Listing
June 2020
5.139 Impact Factor

CRISPR artificial splicing factors.

Nat Commun 2020 Jun 12;11(1):2973. Epub 2020 Jun 12.

The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA.

Alternative splicing allows expression of mRNA isoforms from a single gene, expanding the diversity of the proteome. Its prevalence in normal biological and disease processes warrant precise tools for modulation. Here we report the engineering of CRISPR Artificial Splicing Factors (CASFx) based on RNA-targeting CRISPR-Cas systems. Read More

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http://dx.doi.org/10.1038/s41467-020-16806-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293279PMC

Effects of nusinersen after one year of treatment in 123 children with SMA type 1 or 2: a French real-life observational study.

Orphanet J Rare Dis 2020 Jun 12;15(1):148. Epub 2020 Jun 12.

Centre de Référence des Maladies Neuromusculaires Nord/Ile de France/Est, Service de Neurologie pédiatrique, Hôpital Necker-Enfants Malades, APHP, Paris, France.

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord. Nusinersen has been covered by public healthcare in France since May 2017. The aim of this article is to report results after 1 year of treatment with intrathecal nusinersen in children with SMA types 1 and 2 in France. Read More

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http://dx.doi.org/10.1186/s13023-020-01414-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291731PMC

Sonic Hedgehog-Gli1 Signaling and Cellular Retinoic Acid Binding Protein 1 Gene Regulation in Motor Neuron Differentiation and Diseases.

Int J Mol Sci 2020 Jun 9;21(11). Epub 2020 Jun 9.

Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.

Cellular retinoic acid-binding protein 1 (CRABP1) is highly expressed in motor neurons. Degenerated motor neuron-like MN1 cells are engineered by introducing SOD or AR-65Q to model degenerated amyotrophic lateral sclerosis (ALS) or spinal bulbar muscular atrophy neurons. Retinoic acid (RA)/sonic hedgehog (Shh)-induced embryonic stem cells differentiation into motor neurons are employed to study up-regulation of by Shh. Read More

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http://dx.doi.org/10.3390/ijms21114125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312406PMC

Motoneuronal Spinal Circuits in Degenerative Motoneuron Disease.

Front Mol Neurosci 2020 25;13:74. Epub 2020 May 25.

Section on Developmental Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.

The most evident phenotype of degenerative motoneuron disease is the loss of motor function which accompanies motoneuron death. In both amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), it is now clear that dysfunction is not restricted to motoneurons but is manifest in the spinal circuits in which motoneurons are embedded. As mounting evidence shows that motoneurons possess more elaborate and extensive connections within the spinal cord than previously realized, it is necessary to consider the role of this circuitry and its dysfunction in the disease process. Read More

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http://dx.doi.org/10.3389/fnmol.2020.00074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261878PMC

Expanding the clinical and phenotypic heterogeneity associated with biallelic variants in ACO2.

Ann Clin Transl Neurol 2020 06 9;7(6):1013-1028. Epub 2020 Jun 9.

Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota.

Objective: We describe the clinical characteristics and genetic etiology of several new cases within the ACO2-related disease spectrum. Mitochondrial aconitase (ACO2) is a nuclear-encoded tricarboxylic acid cycle enzyme. Homozygous pathogenic missense variants in the ACO2 gene were initially associated with infantile degeneration of the cerebrum, cerebellum, and retina, resulting in profound intellectual and developmental disability and early death. Read More

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http://dx.doi.org/10.1002/acn3.51074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318087PMC

Minor snRNA gene delivery improves the loss of proprioceptive synapses on SMA motor neurons.

JCI Insight 2020 Jun 18;5(12). Epub 2020 Jun 18.

Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA.

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder caused by reduced expression of the survival motor neuron (SMN) protein. SMN has key functions in multiple RNA pathways, including the biogenesis of small nuclear ribonucleoproteins that are essential components of both major (U2-dependent) and minor (U12-dependent) spliceosomes. Here we investigated the specific contribution of U12 splicing dysfunction to SMA pathology through selective restoration of this RNA pathway in mouse models of varying phenotypic severity. Read More

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http://dx.doi.org/10.1172/jci.insight.130574DOI Listing

Clinical Course in a Patient With Spinal Muscular Atrophy Type 0 Treated With Nusinersen and Onasemnogene Abeparvovec.

J Child Neurol 2020 Jun 9:883073820928784. Epub 2020 Jun 9.

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Spinal muscular atrophy type 0 is the most severe phenotype of the disease, with patients presenting with contractures, weakness, and respiratory failure at birth, and is typically fatal within weeks. We describe the case of a patient with spinal muscular atrophy type 0 who was treated with both nusinersen and onasemnogene abeparvovec. She has made modest motor improvements since treatment initiation with a 30-point improvement in CHOP-INTEND score, and continues to make motor gains at age 13 months without regression of function, although she remains profoundly weak. Read More

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http://dx.doi.org/10.1177/0883073820928784DOI Listing

Prenusinersen economic and health-related quality of life burden of spinal muscular atrophy.

Neurology 2020 Jul 8;95(1):e1-e10. Epub 2020 Jun 8.

From the National Perinatal Epidemiology and Statistics Unit (G.M.C., S.N.S.), School of Women's and Children's Health and the Centre for Big Data Research in Health, University of New South Wales (UNSW) Sydney; Discipline of Paediatrics (K.A.C., M.A.F.), School of Women's and Children's Health, UNSW Medicine, UNSW Sydney; Department of Neurology (M.A.F.), Sydney Children's Hospital Randwick; Neurosciences Department (A.C.), Queensland Children's Hospital; Department of Neurology (M.P.M.), Children's Hospital at Westmead; University of Sydney (M.P.M.), New South Wales; Neurosciences Research (M.R.), Murdoch Children's Research Institute, Melbourne, Victoria; and Department of Paediatrics (M.R.), University of Melbourne, Parkville, Victoria, Australia.

Objective: To quantify the economic and health-related quality of life (HRQoL) burden incurred by households with a child affected by spinal muscular atrophy (SMA).

Methods: Hospital records, insurance claims, and detailed resource use questionnaires completed by caregivers were used to capture the direct and indirect costs to households of 40 children affected by SMA I, II, and III in Australia between 2016 and 2017. Prevalence costing methods were used and reported in 2017 US dollar (USD) purchasing power parity (PPP). Read More

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http://dx.doi.org/10.1212/WNL.0000000000009715DOI Listing

Spinal muscular atrophy: Nature or nurture?

Neurology 2020 Jul 8;95(1):11-12. Epub 2020 Jun 8.

From the Hacettepe Children's Hospital (H.T.), Ankara, Turkey; and Ann and Robert H. Lurie Children's Hospital (N.K.), Chicago, IL. H.T. is currently at the Department of Pediatrics, Yeditepe University, İstanbul, Turkey.

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http://dx.doi.org/10.1212/WNL.0000000000009716DOI Listing

Cell-Clearing Systems Bridging Repeat Expansion Proteotoxicity and Neuromuscular Junction Alterations in ALS and SBMA.

Int J Mol Sci 2020 Jun 4;21(11). Epub 2020 Jun 4.

Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy.

The coordinated activities of autophagy and the ubiquitin proteasome system (UPS) are key to preventing the aggregation and toxicity of misfold-prone proteins which manifest in a number of neurodegenerative disorders. These include proteins which are encoded by genes containing nucleotide repeat expansions. In the present review we focus on the overlapping role of autophagy and the UPS in repeat expansion proteotoxicity associated with chromosome 9 open reading frame 72 () and androgen receptor () genes, which are implicated in two motor neuron disorders, amyotrophic lateral sclerosis (ALS) and spinal-bulbar muscular atrophy (SBMA), respectively. Read More

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http://dx.doi.org/10.3390/ijms21114021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312203PMC

Whole blood survival motor neuron protein levels correlate with severity of denervation in spinal muscular atrophy.

Muscle Nerve 2020 Jun 8. Epub 2020 Jun 8.

Department of Neurology, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts.

Introduction: We sought to determine whether survival motor neuron (SMN) protein blood levels correlate with denervation and SMN2 copies in spinal muscular atrophy (SMA).

Methods: Using a mixed-effect model, we tested associations between SMN levels, compound muscle action potential (CMAP), and SMN2 copies in a cohort of 74 patients with SMA. We analyzed a subset of 19 of these patients plus four additional patients who had been treated with received gene therapy to examine SMN trajectories early in life. Read More

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http://dx.doi.org/10.1002/mus.26995DOI Listing

Assessment of the association between paraspinal muscle degeneration and quality of life in patients with degenerative lumbar scoliosis.

Exp Ther Med 2020 Jul 23;20(1):505-511. Epub 2020 Apr 23.

Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.

The present study aimed to determine the characteristics of multifidus, erector spinae and psoas major degeneration in elderly patients with degenerative lumbar scoliosis (DLS) and the correlation between asymmetric changes and patient quality of life. A total of 49 patients with lumbar scoliosis (DLS group) and 38 healthy individuals (control group) were prospectively examined. The functional cross-sectional area, cross-sectional area difference index (CDI) and fat infiltration rate (FIR) of the multifidus, erector spinae and psoas major at the apical vertebral level were measured using MRI. Read More

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http://dx.doi.org/10.3892/etm.2020.8682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271738PMC

Molecular inversion probe-rolling circle amplification with single-strand poly-T luminescent copper nanoclusters for fluorescent detection of single-nucleotide variant of SMN gene in diagnosis of spinal muscular atrophy.

Anal Chim Acta 2020 Aug 13;1123:56-63. Epub 2020 Apr 13.

School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC; Food and Drug Administration, Ministry of Health and Welfare, Taipei, Taiwan, ROC. Electronic address:

In this study, a simple fluorescent detection of survival motor neuron gene (SMN) in diagnosis of spinal muscular atrophy (SMA) based on nucleic acid amplification test and the poly-T luminescent copper nanoclusters (CuNCs) was established. SMA is a severely genetic diseases to cause infant death in clinical, and detection of SMN gene is a powerful tool for pre- and postnatal diagnosis of this disease. This study utilized the molecular inversion probe for recognition of nucleotide variant between SMN1 (c. Read More

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http://dx.doi.org/10.1016/j.aca.2020.04.026DOI Listing

Survey of patients with spinal muscular atrophy on the island of Shikoku, Japan.

Brain Dev 2020 Jun 3. Epub 2020 Jun 3.

Department of Pediatrics, Ehime University Graduate School of Medicine, Ehime, Japan.

Background: Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder associated with spinal motor neuron loss and characterized by generalized muscle weakness. Only a few reports exist on SMA epidemiology in Japan. Additionally, nusinersen recently became available as a treatment for this condition. Read More

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http://dx.doi.org/10.1016/j.braindev.2020.05.004DOI Listing

Split-hand phenomenon in motor neuron diseases: Sonographic assesment of muscle thickness.

Clin Neurophysiol 2020 May 22;131(8):1721-1725. Epub 2020 May 22.

Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, Canada; Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Objective: To explore the diagnostic accuracy of the split-hand index (SHI) for amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) using sonographic assessment of muscle thickness.

Methods: We performed a prospective sonographic assessment of hand muscle thickness in 59 controls, 87 patients with ALS, and 33 patients with SMA. We determined the diagnostic accuracy of SHI for differentiating patients with ALS and SMA from controls. Read More

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http://dx.doi.org/10.1016/j.clinph.2020.04.163DOI Listing

Sleep surgery in syndromic and neurologically impaired children.

Am J Otolaryngol 2020 Jul - Aug;41(4):102566. Epub 2020 May 27.

Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, United States of America. Electronic address:

Purpose: To examine surgery performed for obstructive sleep apnea (OSA) in children with syndromic or neurologic comorbidities.

Material And Methods: Medical records of 375 children with OSA were retrospectively reviewed, including 142 patients with trisomy 21, 105 with cerebral palsy, 53 with muscular dystrophy, 32 with spinal muscular atrophy, 18 with mucopolysaccharidoses, 14 with achondroplasia, and 11 with Prader-Willi.

Outcome Measures: Apnea-hypopnea index (AHI), complications, length of postoperative stay, and endoscopic findings. Read More

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http://dx.doi.org/10.1016/j.amjoto.2020.102566DOI Listing

Great expectations: virus-mediated gene therapy in neurological disorders.

J Neurol Neurosurg Psychiatry 2020 Jun 5. Epub 2020 Jun 5.

Neurology, Sydney Children's Hospital Randwick, Randwick, New South Wales, Australia

Gene therapy (GT) has tremendous potential for the treatment of neurological disorders to transform patient care. The successful application of virus-mediated GT to treat spinal muscular atrophy is a significant milestone, serving to accelerate similar progress in a spectrum of neurological conditions, with more than 50 clinical trials currently underway, across neurodevelopmental, neurodegenerative, muscular dystrophy, epilepsy, chronic pain and neoplastic diseases. This review provides an overview of the key features of virus-mediated GT, paradigms of delivery and dosing, potential risks and highlights ongoing research to optimise safe and effective delivery of vectors into the nervous system. Read More

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http://dx.doi.org/10.1136/jnnp-2019-322327DOI Listing

Early Results of a Management Algorithm for Collapsing Spine Deformity in Young Children (Below 10-Year Old) With Spinal Muscular Atrophy Type II.

J Pediatr Orthop 2020 Jul;40(6):e413-e419

Department of Orthopaedics and Traumatology, Hacettepe University School of Medicine, Ankara, Turkey.

Background: Progressive C-shaped scoliosis with marked pelvic obliquity is common to spinal muscular atrophy (SMA). Reducing the number of procedures with effective deformity control is critical to minimize the risk of pulmonary complications. This study reports the preliminary results of magnetically controlled growing rods (MCGR) in SMA-related collapsing spine deformity. Read More

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http://dx.doi.org/10.1097/BPO.0000000000001489DOI Listing