7,998 results match your criteria Spinal Muscular Atrophy


Carrier frequency of spinal muscular atrophy in Thailand.

Neurol Sci 2019 Apr 19. Epub 2019 Apr 19.

Department of Internal Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Spinal muscular atrophy (SMA) is one of the leading causes of death in infants and young children from heritable diseases. Patients diagnosed with SMA develop symmetrical progressive muscle weakness and atrophy from degeneration of alpha motor neurons. Approximately 95% of patients have a homozygous deletion of survival motor neuron 1 (SMN1) gene in exon 7 and inherited in autosomal recessive pattern. Read More

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http://link.springer.com/10.1007/s10072-019-03885-5
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http://dx.doi.org/10.1007/s10072-019-03885-5DOI Listing
April 2019
1 Read

High-intensity training in patients with spinal and bulbar muscular atrophy.

J Neurol 2019 Apr 19. Epub 2019 Apr 19.

Department of Neurology, Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.

Objective: Long duration, moderate-intensity exercise is not well tolerated in patients with spinal and bulbar muscular atrophy (SBMA). This study investigated whether patients with SBMA can benefit from high-intensity training (HIT).

Methods: Ten patients with SBMA were randomized to 8 weeks of supervised HIT [n = 5; age = 50 (25-63) years] followed by 8 weeks of self-training or 8 weeks of no training followed by 8 weeks of non-supervised HIT [n = 5; age = 50 (26-54) years]. Read More

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http://dx.doi.org/10.1007/s00415-019-09316-xDOI Listing
April 2019
2 Reads

Lumbar laminotomy for the intrathecal administration of nusinersen for spinal muscular atrophy: technical note and outcomes.

J Neurosurg Spine 2019 Apr 19:1-5. Epub 2019 Apr 19.

3Neurological Surgery, Oregon Health & Science University, Portland, Oregon.

Nusinersen (Spinraza) is a US Food and Drug Administration-approved intrathecal medication for the treatment of spinal muscular atrophy (SMA). Adult patients with SMA often undergo thoracolumbar fusion to treat neurogenic scoliosis, preventing thecal access. The authors report a laminotomy technique and the ease of intrathecal access in three SMA patients with prior thoracolumbar fusions. Read More

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https://thejns.org/view/journals/j-neurosurg-spine/aop/artic
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http://dx.doi.org/10.3171/2019.2.SPINE181366DOI Listing
April 2019
1 Read

Permittivity of ex vivo healthy and diseased murine skeletal muscle from 10 kHz to 1 MHz.

Sci Data 2019 Apr 18;6(1):37. Epub 2019 Apr 18.

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA.

A better understanding of the permittivity property of skeletal muscle is essential for the development of new diagnostic tools and approaches for neuromuscular evaluation. However, there remain important knowledge gaps in our understanding of this property in healthy and diseased skeletal muscle, which hinder its translation into clinical application. Here, we report the permittivity of gastrocnemius muscle in healthy wild type mice and murine models of spinal muscular atrophy, muscular dystrophy, diabetes, amyotrophic lateral sclerosis and in a model of myofiber hypertrophy. Read More

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http://www.nature.com/articles/s41597-019-0045-2
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http://dx.doi.org/10.1038/s41597-019-0045-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472406PMC
April 2019
1 Read

Long-term Effects of Androgen Deprivation in a Patient with Spinal and Bulbar Muscular Atrophy - A Case Report with 14 Years of Follow-up.

Intern Med 2019 Apr 17. Epub 2019 Apr 17.

Department of Neurology, Nagoya University Graduate School of Medicine, Japan.

Spinal and bulbar muscular atrophy (SBMA) is a progressive hereditary neuromuscular disease caused by the testosterone-dependent accumulation of pathogenic polyglutamine-expanded androgen receptor protein. A 41-year-old man with SBMA received the androgen deprivation agent leuprorelin acetate for 7 years in clinical trials and underwent castration following the trial. Suppression of testosterone levels for 14 years resulted in a slower disease progression, as measured prospectively with quantitative measurements, than the historical control data reported in previous studies. Read More

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http://dx.doi.org/10.2169/internalmedicine.1592-18DOI Listing

In vivo assembly of eukaryotic signal recognition particle: A still enigmatic process involving the SMN complex.

Biochimie 2019 Apr 9. Epub 2019 Apr 9.

Ingénierie Moléculaire et Physiopathologie Articulaire, UMR 7365 CNRS-University of Lorraine, Biopôle de l'Université de Lorraine, Campus Brabois-Santé, 9 avenue de la forêt de Haye, BP 20199, 54505 Vandoeuvre-les-Nancy, France. Electronic address:

The signal recognition particle (SRP) is a universally conserved non-coding ribonucleoprotein complex that is essential for targeting transmembrane and secretory proteins to the endoplasmic reticulum. Its composition and size varied during evolution. In mammals, SRP contains one RNA molecule, 7SL RNA, and six proteins: SRP9, 14, 19, 54, 68 and 72. Read More

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http://dx.doi.org/10.1016/j.biochi.2019.04.007DOI Listing

A Novel Pharyngeal Clearance Maneuver for Initial Tracheostomy Tube Cuff Deflation in High Cervical Tetraplegia.

Am J Phys Med Rehabil 2019 Apr 9. Epub 2019 Apr 9.

Rehabilitation Research Center at Santa Clara Valley Medical Center, San Jose, CA.

Mechanical insufflation-exsufflation (MIE), or "cough-assist" is a commonly used method of clearing tracheal and pulmonary secretions in patients with respiratory insufficiency secondary to spinal cord injury (SCI). This report presents a novel technique termed the Pharyngeal Clearance Maneuver (PCM) which utilizes a modified application of the MIE device to mobilize "secretion burden" at the portion of the trachea above the tracheostomy cuff during cuff deflation. Utilization of this strategy may reduce the risk of aspiration, infection, and respiratory compromise for patients with high cervical SCI in the acute rehabilitation setting. Read More

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http://dx.doi.org/10.1097/PHM.0000000000001192DOI Listing
April 2019
1 Read

Smooth muscle atrophy and colon pathology in SMN deficient mice.

Am J Transl Res 2019 15;11(3):1789-1799. Epub 2019 Mar 15.

Department of Physiology, University of Pennsylvania Perelman School of Medicine Philadelphia, PA.

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder characterized by loss of motor neurons in the ventral horn of the spinal cord. Clinical features such as progressively lethal respiratory weakness and associated muscle wasting have been extensively studied but less attention has been given to gastrointestinal (GI) dysfunction, which is common symptomatology in SMA patients with 43% constipation, 15% abdominal pain, and 14% meteorism. In the current study, the PrP92-SMN mouse model of SMA was utilized, to complement previous studies in which cells of the Enteric Nervous system (ENS) were susceptible to Smn (survival motor neuron) deficiency and could possibly be the basis of the observed GI symptoms. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456546PMC
March 2019
3 Reads

ACTIVE (Ability Captured Through Interactive Video Evaluation) workspace volume video game to quantify meaningful change in spinal muscular atrophy.

Dev Med Child Neurol 2019 Apr 8. Epub 2019 Apr 8.

Center for Gene Therapy, Nationwide Children's Hospital, Columbus, OH, USA.

Aim: To evaluate the utility of Ability Captured Through Interactive Video Evaluation (ACTIVE) scaled scores to quantify meaningful change in individuals with spinal muscular atrophy (SMA) types 2 or 3 due to disease progression or treatment.

Method: ACTIVE is a custom-designed video game that measures workspace volume (WSV). Participants included 62 individuals with SMA (mean age [SD] 10y 9mo [5y], range 2y 9mo-24y) and 362 frequency-matched controls (mean age [SD] 10y 9mo [3y 6mo], range 3y 2mo-24y 9mo). Read More

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http://dx.doi.org/10.1111/dmcn.14230DOI Listing
April 2019
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Quality of life of patients with spinal muscular atrophy: A systematic review.

Eur J Paediatr Neurol 2019 Mar 21. Epub 2019 Mar 21.

Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.

Objectives: To systematically review the literature of quality of life (QoL) of patients with spinal muscular atrophy (SMA), a rare, autosomal-recessive neuromuscular disease associated with extensive morbidity and elevated mortality.

Methods: We searched Embase, Web of Science, and PubMed for full-text, English-language articles (published between January 1, 2000 and July 31, 2018) reporting results from studies of QoL of patients with SMA. We excluded review and editorial articles, studies reporting results for samples comprising <5 patients (to allow for meaningful inference), and case reports/qualitative assessments. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10903798193000
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http://dx.doi.org/10.1016/j.ejpn.2019.03.004DOI Listing
March 2019
1 Read

Participation and mental well-being of mothers of home-living patients with spinal muscular atrophy.

Neuromuscul Disord 2019 Apr 2;29(4):321-329. Epub 2019 Mar 2.

Center of Excellence for Rehabilitation Medicine, UMC Utrecht Brain Center, University Medical Center Utrecht, and De Hoogstraat Rehabilitation, Utrecht, The Netherlands; Department of Rehabilitation, Physical Therapy Science and Sports, Brain Center Rudolf Magnus, University Medical Center Utrecht, Postbus 85500, 3508 GA Utrecht, The Netherlands.

Proximal spinal muscular atrophy (SMA) causes severe physical limitations but also has a major impact on the lives of parents. The aim of this study was to investigate participation and mental well-being (burden, emotional distress and satisfaction with participation) of parents of home-living patients with SMA. Caregiver burden was assessed with the Caregiver Strain Index, emotional distress with the Hospital Anxiety and Depression Scale and satisfaction with participation with the Utrecht Scale for Evaluation of Rehabilitation-Participation. Read More

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http://dx.doi.org/10.1016/j.nmd.2019.02.011DOI Listing
April 2019
1 Read

Communication skills among children with spinal muscular atrophy type 1: A parent survey.

Assist Technol 2019 Apr 4:1-11. Epub 2019 Apr 4.

b Department of Physical Medicine and Rehabilitation, Children's National Health System , Washington DC , USA.

Spinal muscular atrophy is one of the most common fatal autosomal recessive disorders. Children diagnosed with SMA Type 1 (SMAT1) demonstrate severe oral motor weakness and flaccid dysarthria progressing to complete anarthria. A review of literature illustrates that little has been described regarding augmentative and alternative communication (AAC) use among these children, although communication has a critical impact on quality of life and participation in daily activities. Read More

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https://www.tandfonline.com/doi/full/10.1080/10400435.2019.1
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http://dx.doi.org/10.1080/10400435.2019.1586788DOI Listing
April 2019
2 Reads

[Effect of electroacupuncture on muscular atrophy and Slit/Robo signaling in sciatic nerve and lumbar spinal cord tissues in rats with sciatic nerve injury].

Zhen Ci Yan Jiu 2019 Feb;44(2):102-6

Department of Acupuncture-moxibustion and Tuina, Shaanxi University of Traditional Chinese Medicine, Xianyang 712046, Shaanxi Province, China.

Objective: To observe the effect of electroacupuncture (EA) of "Huantiao"(GB30) and" Zusanli"(ST36)on muscular atrophy and expression of Slit-Robo GTPase-activating protein(srGAP)1, 2 and 3 in the injured sciatic nerve and lumbar spinal cord tissues in sciatic nerve injury (SNI) rats, so as to reveal its mechanisms underlying improvement of peripheral nerve injury (PNI)..

Methods: A total of 120 healthy male SD rats were randomly divided into control, sham-operation, model and EA groups (=30 rats in each) which were further divided into 7, 15 and 23 d subgroups (=10 rats in each subgroup). The SNI model was established by transecting the right sciatic nerve beneath the piriformis and immediately subsequent end-to-end suture. Read More

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http://www.cnki.net/kcms/doi/10.13702/j.1000-0607.180186.htm
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http://dx.doi.org/10.13702/j.1000-0607.180186DOI Listing
February 2019
4 Reads

Monitoring Kidney Dysfunction in Kugelberg-Welander Syndrome.

Am J Case Rep 2019 Apr 3;20:441-446. Epub 2019 Apr 3.

Kidney Transplant Program, St. Michael's Hospital, Toronto, Canada.

BACKGROUND Kugelberg-Welander (K-W) syndrome is a type of spinal muscular atrophy that causes weakness of the hip-girdle muscles. If severe enough, this weakness can confine patients to a wheelchair in adult life. Proteinuria, a manifestation of kidney dysfunction, is associated with disorders of many organ systems. Read More

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http://dx.doi.org/10.12659/AJCR.914458DOI Listing
April 2019
2 Reads

DNA methylation inhibitor attenuates polyglutamine-induced neurodegeneration by regulating Hes5.

EMBO Mol Med 2019 Apr 1. Epub 2019 Apr 1.

Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan

Spinal and bulbar muscular atrophy (SBMA) is a polyglutamine-mediated neuromuscular disease caused by a CAG repeat expansion in the () gene. While transcriptional dysregulation is known to play a critical role in the pathogenesis of SBMA, the underlying molecular pathomechanisms remain unclear. DNA methylation is a fundamental epigenetic modification that silences the transcription of various genes that have a CpG-rich promoter. Read More

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http://dx.doi.org/10.15252/emmm.201708547DOI Listing
April 2019
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"Getting ready for the adult world": how adults with spinal muscular atrophy perceive and experience healthcare, transition and well-being.

Orphanet J Rare Dis 2019 Apr 2;14(1):74. Epub 2019 Apr 2.

Discipline of Paediatrics, School of Women's and Children's Health, UNSW Medicine, UNSW Sydney, Randwick, Australia.

Background: Spinal muscular atrophy (SMA) has profound implications across a lifetime for people with the condition and their families. Those affected need long-term multidisciplinary medical and supportive care to maintain functional mobility, independence and quality of life. Little is known about how adults with SMA experience healthcare, or the components of care perceived as important in promoting well-being. Read More

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http://dx.doi.org/10.1186/s13023-019-1052-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446316PMC
April 2019
1 Read

Prevalence of Carriers of Intermediate and Pathological Polyglutamine Disease-Associated Alleles Among Large Population-Based Cohorts.

JAMA Neurol 2019 Apr 1. Epub 2019 Apr 1.

German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Importance: Nine hereditary neurodegenerative diseases are known as polyglutamine diseases, including Huntington disease, 6 spinocerebellar ataxias (SCAs) (SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17), dentatorubral-pallidoluysion atrophy, and spinal bulbar muscular atrophy.

Objective: To determine the prevalence of carriers of intermediate and pathological polyglutamine disease-associated alleles among the general population.

Design, Setting, And Participants: This observational cross-sectional study included data from 5 large European population-based cohorts that were compiled between 1997 and 2012, and the analyses were conducted in 2018. Read More

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http://dx.doi.org/10.1001/jamaneurol.2019.0423DOI Listing
April 2019
2 Reads

Scoliosis and spinal muscular atrophy in the new world of medical therapy: providing lumbar access for intrathecal treatment in patients previously treated or undergoing spinal instrumentation and fusion.

J Pediatr Orthop B 2019 Mar 29. Epub 2019 Mar 29.

Department of Orthopedics, University of Iowa, Iowa City, Iowa, USA.

This study describes a new procedure for a safer and easier access for the intrathecal injection of the recently approved nusinersen therapy in spinal muscular atrophy. This therapy changed the natural history of the disease, but, to date, scoliosis surgery was an excluding criteria for nusinersen therapy. The bone mass, due to the posterior spinal fusion of the scoliosis surgery, prevents the needle for the Nusinersen administration from intervertebral access This is a single-center, single-surgeon case series descriptive study. Read More

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http://dx.doi.org/10.1097/BPB.0000000000000632DOI Listing

Validation of a multiplexed LC-MS/MS clinical assay to quantify insulin-like growth factor-binding proteins in human serum and its application in a clinical study.

Toxicol Appl Pharmacol 2019 Mar 26;371:74-83. Epub 2019 Mar 26.

Nextcea Inc., 500 West Cummings Park #4550, Woburn, MA 01801, USA. Electronic address:

Circulating insulin-like growth factor-binding proteins (IGFBPs) continue to gain attention as biomarkers of drug activities on insulin like growth factor (IGF)/IGF receptor signaling pathways. A multiplexed LC-MS/MS method was validated for the absolute quantitation of IGFBPs in human serum. The method was used to measure screening concentrations of IGFBPs in spinal and bulbar muscular atrophy (SBMA) patients in a phase 2 clinical trial. Read More

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http://dx.doi.org/10.1016/j.taap.2019.03.024DOI Listing
March 2019
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NMR solution structure of tricyclo-DNA containing duplexes: insight into enhanced thermal stability and nuclease resistance.

Nucleic Acids Res 2019 Mar 27. Epub 2019 Mar 27.

Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, Bern CH-3012, Switzerland.

Tc-DNA is a conformationally constrained oligonucleotide analogue which shows significant increase in thermal stability when hybridized with RNA, DNA or tc-DNA. Remarkably, recent studies revealed that tc-DNA antisense oligonucleotides (AO) hold great promise for the treatment of Duchenne muscular dystrophy and spinal muscular atrophy. To date, no high-resolution structural data is available for fully modified tc-DNA duplexes and little is known about the origins of their enhanced thermal stability. Read More

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http://dx.doi.org/10.1093/nar/gkz197DOI Listing
March 2019
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Preliminary design and validation of the "6-K-scale" for bulbar symptoms evaluation in SBMA.

Neurol Sci 2019 Mar 26. Epub 2019 Mar 26.

Neuromuscular Center, Department of Neurosciences, University of Padova, Padua, Italy.

Background: Spinal and bulbar muscular atrophy (SBMA) is a late onset, X-linked neuromuscular disease. Bulbar symptoms are a main characteristic of the disease but a tool for their clinical evaluation still does not exist. The aim of this study was to design and test a new scale (6-K-scale) for evaluation of bulbar function in SBMA. Read More

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http://dx.doi.org/10.1007/s10072-019-03850-2DOI Listing

Trends in incidence, prevalence, and mortality of neuromuscular disease in Ontario, Canada: A population-based retrospective cohort study (2003-2014).

PLoS One 2019 26;14(3):e0210574. Epub 2019 Mar 26.

Institute of Clinical Evaluative Sciences, Toronto, Canada.

Background: Population trends of disease prevalence and incidence over time measure burden of disease and inform healthcare planning. Neuromuscular disorders (NMD) affect muscle and nerve function with varying degrees of severity and disease progression.

Objective: Using health administrative databases we described trends in incidence, prevalence, and mortality of adults and children with NMD. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210574PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435115PMC
March 2019
1 Read

Drug screening with human SMN2 reporter identifies SMN protein stabilizers to correct SMA pathology.

Life Sci Alliance 2019 Apr 25;2(2). Epub 2019 Mar 25.

Department of Biomedical Sciences, University of Illinois College of Medicine Rockford, Rockford, IL, USA

Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, is caused by reduced levels of functional survival motor neuron (SMN) protein. To identify therapeutic agents for SMA, we established a versatile SMN2-GFP reporter line by targeting the human gene. We then screened a compound library and identified Z-FA-FMK as a potent candidate. Read More

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http://www.life-science-alliance.org/lookup/doi/10.26508/lsa
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http://dx.doi.org/10.26508/lsa.201800268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435041PMC
April 2019
5 Reads

[Association of copy number of SMN1 and SMN2 with clinical phenotypes in children with spinal muscular atrophy].

Zhongguo Dang Dai Er Ke Za Zhi 2019 Mar;21(3):239-243

Genetic Diagnosis Center, Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China.

Objective: To study the association of copy number of SMN1 and SMN2 with clinical phenotypes in children with spinal muscular atrophy (SMA).

Methods: A total of 45 children with SMA were enrolled. Multiplex ligation-dependent probe amplification was used to measure the gene copy numbers of SMN1 and SMN2. Read More

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March 2019
2 Reads

Prediction of key gene function in spinal muscular atrophy using guilt by association method based on network and gene ontology.

Exp Ther Med 2019 Apr 29;17(4):2561-2566. Epub 2019 Jan 29.

Sports Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266071, P.R. China.

Guilt by association (GBA) algorithm has been widely used to predict gene functions statistically, and a network-based approach may increase the confidence and veracity of identifying molecular signatures for diseases. The aim of the present study was to suggest a gene ontology (GO)-based method by integrating the GBA algorithm and network, to identify key gene functions for spinal muscular atrophy (SMA). The inference of predicting key gene functions was comprised of four steps, preparing gene lists and sets; extracting differentially expressed genes (DEGs) using microarray data [linear models for microarray data (limma)] package; constructing a co-expression matrix on gene lists using the Spearman correlation coefficient method; and predicting gene functions by GBA algorithm. Read More

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http://dx.doi.org/10.3892/etm.2019.7216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425128PMC
April 2019
2 Reads

Progress in treatment and newborn screening for Duchenne muscular dystrophy and spinal muscular atrophy.

World J Pediatr 2019 Mar 23. Epub 2019 Mar 23.

Department of Neurology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 673, Rochester, NY, 14642, USA.

Background: Advances in treatment for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) hold promise for children with these disorders. Accurate genetic diagnosis, early in the disease process, will allow these treatments to be most effective. Newborn screening (NBS) for SMA has been recommended in the United States, and a pilot DMD NBS program is underway in Hangzhou, China. Read More

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http://link.springer.com/10.1007/s12519-019-00242-6
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http://dx.doi.org/10.1007/s12519-019-00242-6DOI Listing
March 2019
8 Reads

Is there hope for spinal muscular atrophy synthetic pharmacotherapy?

Authors:
Markus Riessland

Expert Opin Pharmacother 2019 Mar 20:1-4. Epub 2019 Mar 20.

a Laboratory of Molecular and Cellular Neuroscience , The Rockefeller University , New York , NY , USA.

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http://dx.doi.org/10.1080/14656566.2019.1595585DOI Listing

Molecular Mechanisms Underlying Sensory-Motor Circuit Dysfunction in SMA.

Front Mol Neurosci 2019 4;12:59. Epub 2019 Mar 4.

Edinburgh Medical School: Biomedical Sciences, The University of Edinburgh, Edinburgh, United Kingdom.

Activation of skeletal muscle in response to acetylcholine release from the neuromuscular junction triggered by motor neuron firing forms the basis of all mammalian locomotion. Intricate feedback and control mechanisms, both from within the central nervous system and from sensory organs in the periphery, provide essential inputs that regulate and finetune motor neuron activity. Interestingly, in motor neuron diseases, such as spinal muscular atrophy (SMA), pathological studies in patients have identified alterations in multiple parts of the sensory-motor system. Read More

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http://dx.doi.org/10.3389/fnmol.2019.00059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409332PMC
March 2019
10 Reads

Turning the tide in spinal muscular atrophy: A different respiratory course.

Authors:
Oscar H Mayer

Pediatr Pulmonol 2019 Mar 18. Epub 2019 Mar 18.

Division of Pulmonology, The Children's Hospital of Philadelphia, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1002/ppul.24315DOI Listing

Rewriting the (tran)script: Application to spinal muscular atrophy.

Prog Med Chem 2019 1;58:119-156. Epub 2019 Feb 1.

F. Hoffmann-La Roche Ltd., pRED, Pharma Research & Early Development, Roche Innovation Center Basel, Basel, Switzerland.

Targeting RNA drastically expands our target space to therapeutically modulate numerous cellular processes implicated in human diseases. Of particular interest, drugging pre-mRNA splicing appears a very viable strategy; to control levels of splicing product by promoting the inclusion or exclusion of exons. After describing the concept of "splicing modulation", this chapter will cover the outstanding progress achieved in this field, by highlighting the breakthrough accomplished recently for the treatment of spinal muscular atrophy using two therapeutic modalities: splice switching oligonucleotides and small molecules. Read More

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http://dx.doi.org/10.1016/bs.pmch.2018.12.003DOI Listing

Survival, Motor Function, and Motor Milestones: Comparison of AVXS-101 Relative to Nusinersen for the Treatment of Infants with Spinal Muscular Atrophy Type 1.

Adv Ther 2019 Mar 16. Epub 2019 Mar 16.

AveXis, Inc., Bannockburn, IL, USA.

Introduction: Infants with spinal muscular atrophy (SMA) type 1 typically face a decline in motor function and a severely shortened life expectancy. Clinical trials for SMA type 1 therapies, onasemnogene abeparvovec (AVXS-101) and nusinersen, demonstrated meaningful improvements in efficacy (e.g. Read More

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http://dx.doi.org/10.1007/s12325-019-00923-8DOI Listing
March 2019
1 Read

Disease Affects Expression in Synaptic and Extrasynaptic Regions of Skeletal Muscle of Three SBMA Mouse Models.

Int J Mol Sci 2019 Mar 15;20(6). Epub 2019 Mar 15.

Neuroscience Program, 108 Giltner Hall, Michigan State University, East Lansing, MI 48824-1115, USA.

Spinal bulbar muscular atrophy (SBMA) is a slowly progressive, androgen-dependent neuromuscular disease in men that is characterized by both muscle and synaptic dysfunction. Because gene expression in muscle is heterogeneous, with synaptic myonuclei expressing genes that regulate synaptic function and extrasynaptic myonuclei expressing genes to regulate contractile function, we used quantitative PCR to compare gene expression in these two domains of muscle from three different mouse models of SBMA: the "97Q" model that ubiquitously expresses mutant human androgen receptor (AR), the 113Q knock-in (KI) model that expresses humanized mouse AR with an expanded glutamine tract, and the "myogenic" model that overexpresses wild-type rat AR only in skeletal muscle. We were particularly interested in neurotrophic factors because of their role in maintaining neuromuscular function via effects on both muscle and synaptic function, and their implicated role in SBMA. Read More

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http://dx.doi.org/10.3390/ijms20061314DOI Listing
March 2019
4 Reads

Systemic nature of spinal muscular atrophy revealed by studying insurance claims.

PLoS One 2019 14;14(3):e0213680. Epub 2019 Mar 14.

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, United States of America.

Objective: We investigated the presence of non-neuromuscular phenotypes in patients affected by Spinal Muscular Atrophy (SMA), a disorder caused by a mutation in the Survival of Motor Neuron (SMN) gene, and whether these phenotypes may be clinically detectable prior to clinical signs of neuromuscular degeneration and therefore independent of muscle weakness.

Methods: We utilized a de-identified database of insurance claims to explore the health of 1,038 SMA patients compared to controls. Two analyses were performed: (1) claims from the entire insurance coverage window; and (2) for SMA patients, claims prior to diagnosis of any neuromuscular disease or evidence of major neuromuscular degeneration to increase the chance that phenotypes could be attributed directly to reduced SMN levels. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213680PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417721PMC
March 2019
6 Reads

First case of Roma ethnic origin with Andermann syndrome: A novel frameshift mutation in exon 20 of SLC12A6 gene.

Am J Med Genet A 2019 Mar 13. Epub 2019 Mar 13.

Department of Pediatrics and Medical Genetics, Medical University, Plovdiv, Bulgaria.

Andermann syndrome (AS) is caused by mutation of SLC12A6 gene. It comprises severe progressive sensory and motor neuropathy with early onset, varying degree of agenesis of corpus callosum (ACC) and mental retardation. AS occurs occasionally among population outside the northeastern Quebec-Saguenay-Lac- St-Jean and Charlevoix regions, inhabited by French Canadians. Read More

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http://dx.doi.org/10.1002/ajmg.a.61110DOI Listing

Radiation exposure of image-guided intrathecal administration of nusinersen to adult patients with spinal muscular atrophy.

Neuroradiology 2019 May 14;61(5):565-574. Epub 2019 Mar 14.

Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany.

Purpose: To examine diagnostic reference levels (DRL) and achievable doses (AD) of image-guided and size-specific dose estimates (SSDE) and organ and effective doses of CT-guided intrathecal nusinersen administration to adult patients with spinal muscular atrophy (SMA).

Methods: This study involved a total of 60 image-guided intrathecal nusinersen treatments between August 2017 and June 2018. Patient cohort comprised 14 adult patients with the following SMA types: type 2 (n = 9) and type 3 (n = 5) with a mean age of 33. Read More

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http://dx.doi.org/10.1007/s00234-019-02189-xDOI Listing
May 2019
2 Reads

Diagnostic Odyssey and Application of Targeted Exome Sequencing in the Investigation of Recurrent Infant Deaths in a Syrian Consanguineous Family: a Case of Spinal Muscular Atrophy with Respiratory Distress Type 1.

J Korean Med Sci 2019 Mar 7;34(9):e54. Epub 2019 Feb 7.

Department of Pediatrics, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive disorder caused by a defect in the immunoglobulin mu binding protein 2 () gene, leading to motor neuron degeneration. We identified an infant with SMARD1 by targeted exome sequencing from a consanguineous Syrian family having a history of recurrent infant deaths. The patient initially presented intrauterine growth retardation, poor sucking, failure to thrive, and respiratory failure at the age of two months, and an inborn error of metabolism was suspected at first. Read More

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http://dx.doi.org/10.3346/jkms.2019.34.e54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406039PMC
March 2019
2 Reads

The natural antisense transcript NATTD regulates the transcription of decapping scavenger (DcpS) enzyme.

Int J Biochem Cell Biol 2019 Mar 8;110:103-110. Epub 2019 Mar 8.

From Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China. Electronic address:

Natural antisense transcripts (NATs) are transcribed from the opposite strand of other genes. Most of them are noncoding RNAs. They have been reported to play important roles in a variety of biological processes. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S13572725193005
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http://dx.doi.org/10.1016/j.biocel.2019.03.005DOI Listing
March 2019
10 Reads
4.046 Impact Factor

Neurocalcin Delta Knockout Impairs Adult Neurogenesis Whereas Half Reduction Is Not Pathological.

Front Mol Neurosci 2019 12;12:19. Epub 2019 Feb 12.

Institute of Human Genetics, University of Cologne, Cologne, Germany.

Neurocalcin delta (NCALD) is a brain-enriched neuronal calcium sensor and its reduction acts protective against spinal muscular atrophy (SMA). However, the physiological function of NCALD and implications of NCALD reduction are still elusive. Here, we analyzed the ubiquitous knockout in homozygous () and heterozygous () mice to unravel the physiological role of NCALD in the brain and to study whether 50% NCALD reduction is a safe option for SMA therapy. Read More

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http://dx.doi.org/10.3389/fnmol.2019.00019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396726PMC
February 2019
1 Read

Efficacy and safety of leuprorelin acetate for subjects with spinal and bulbar muscular atrophy: pooled analyses of two randomized-controlled trials.

J Neurol 2019 May 7;266(5):1211-1221. Epub 2019 Mar 7.

Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, showa-ku, Nagoya, Aichi, 466-8550, Japan.

Background: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, hereditary neuromuscular disease characterized by muscle atrophy, weakness, contraction fasciculation, and bulbar involvement. Although the causative gene, androgen receptor, has been identified, the development of novel therapeutics for SBMA is incomplete. In this study, the efficacy and safety of leuprorelin acetate administration for patients with SBMA, using the pooled data of two randomized-controlled trials, was studied. Read More

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http://dx.doi.org/10.1007/s00415-019-09251-xDOI Listing
May 2019
1 Read

A novel mutation associated with recessive distal hereditary motor neuropathy.

Ann Clin Transl Neurol 2019 Feb 3;6(2):401-405. Epub 2018 Dec 3.

Department of Neurology Fujian Medical University Union Hospital Fuzhou 350001 China.

Vaccinia-related kinase 1 () mutations can cause motor phenotypes including axonal sensorimotor neuropathy, distal hereditary motor neuropathy (dHMN), spinal muscular atrophy, and amyotrophic lateral sclerosis. Here, we identify a novel homozygous p.W375X mutation causing recessive dHMN. Read More

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http://dx.doi.org/10.1002/acn3.701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389749PMC
February 2019
1 Read

Notch Signaling Mediates Astrocyte Abnormality in Spinal Muscular Atrophy Model Systems.

Sci Rep 2019 Mar 6;9(1):3701. Epub 2019 Mar 6.

Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of spinal motor neurons and muscle atrophy. The disease is mainly caused by low level of the survival motor neuron (SMN) protein, which is coded by two genes, namely SMN1 and SMN2, but leads to selective spinal motor neuron degeneration when SMN1 gene is deleted or mutated. Previous reports have shown that SMN-protein-deficient astrocytes are abnormally abundant in the spinal cords of SMA model mice. Read More

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http://dx.doi.org/10.1038/s41598-019-39788-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403369PMC
March 2019
1 Read

Effect of new modalities of treatment on physicians management plan for patients with spinal muscular atrophy.

Neurosciences (Riyadh) 2019 Jan;24(1):16-21

Division of Neurology, Department of Pediatrics, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia. E-mail:

Objective: To determine physicians` attitudes and stated practice in the management of patients with spinal muscular atrophy (SMA). We also aimed to explore their knowledge about consensus statement for standard of care in SMA and the role of new treatment modalities in changing the method of practice in the management of these cases.

Methods: This is a quantitative observational cross-sectional study, conducted from February to May 2017 among physicians who manage SMA patients in Kingdom of Saudi Arabia. Read More

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http://dx.doi.org/10.17712/nsj.2019.1.20180321DOI Listing
January 2019

A Short History of Medical Expert Guidelines and How They Pertain to Tracheostomy Tubes and Physical Medicine and Rehabilitation.

Authors:
John R Bach

Am J Phys Med Rehabil 2019 Feb 27. Epub 2019 Feb 27.

Professor of Physical Medicine and Rehabilitation Department of PM&R, Professor of Neurology, Department of Neurology, Medical Director of the Center for Ventilator Management Alternatives and Pulmonary Rehabilitation of the University Hospital, of the Rutgers New Jersey Medical School, Newark, New Jersey, USA.

Continuous noninvasive ventilatory support (CNVS) and mechanical insufflation exsufflation (MIE) have been used since 1953 to spare patients with ventilatory pump failure from ever requiring tracheostomy tubes for ventilatory support or secretion management. Today there are patients with spinal muscular atrophy type 1 who are 25 years old and CNVS dependent since 4 months or age, post-polio survivors CNVS dependent for 64 years, Duchenne muscular dystrophy patients over age 45 CNVS dependent for over 25 years, high level spinal cord injured patients CNVS dependent for over 20 years, and even lung disease patients dependent on CNVS. All these patients, although unweanable from ventilatory support and with little or no measurable vital capacity, can also be extubated to CNVS and MIE without resort to tracheotomies when necessary to continue CNVS. Read More

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http://dx.doi.org/10.1097/PHM.0000000000001172DOI Listing
February 2019
1 Read
2.012 Impact Factor

Prevalence of metabolic syndrome and non-alcoholic fatty liver disease in a cohort of italian patients with spinal-bulbar muscular atrophy.

Acta Myol 2018 Sep 1;37(3):204-209. Epub 2018 Sep 1.

Department of Medicine, University of Padua, Italy.

Spinal-bulbar muscular atrophy (SBMA), is an X-linked motor neuron disease caused by a CAG-repeat expansion in the first exon of the androgen receptor gene (AR) on chromosome X. In SBMA, non-neural clinical phenotype includes disorders of glucose and lipid metabolism. We investigated the prevalence of metabolic syndrome (MS), insulin resistance (IR) and non alcoholic fatty liver disease (NAFLD) in a group of SBMA patients. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390113PMC
September 2018
4 Reads

Gene expression analysis reveals early dysregulation of disease pathways and links Chmp7 to pathogenesis of spinal and bulbar muscular atrophy.

Sci Rep 2019 Mar 5;9(1):3539. Epub 2019 Mar 5.

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK.

Spinal and bulbar muscular atrophy (SBMA) results from a CAG repeat expansion within the androgen receptor gene (AR). It is unclear why motor neurons selectively degenerate and there are currently no treatments for this debilitating disease. To uncover the causative genes and pathways involved in motor neuron dysfunction, we undertook transcriptomic profiling of primary embryonic motor neurons from SBMA mice. Read More

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http://dx.doi.org/10.1038/s41598-019-40118-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401132PMC
March 2019
1 Read

Physical exercise training for type 3 spinal muscular atrophy.

Cochrane Database Syst Rev 2019 Mar 1;3:CD012120. Epub 2019 Mar 1.

Child Development and Exercise Center, Wilhelmina Children's Hospital, University Medical Center Utrecht, Lundlaan 6, Utrecht, Utrecht, Netherlands, 3508 AB.

Background: Physical exercise training might improve muscle and cardiorespiratory function in spinal muscular atrophy (SMA). Optimization of aerobic capacity or other resources in residual muscle tissue through exercise may counteract the muscle deterioration that occurs secondary to motor neuron loss and inactivity in SMA. There is currently no evidence synthesis available on physical exercise training in people with SMA type 3. Read More

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http://dx.doi.org/10.1002/14651858.CD012120.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396106PMC
March 2019
3 Reads

The New Paradigms in Clinical Research: From Early Access Programs to the Novel Therapeutic Approaches for Unmet Medical Needs.

Front Pharmacol 2019 13;10:111. Epub 2019 Feb 13.

Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Naples, Italy.

Despite several innovative medicines gaining worldwide approval in recent years, there are still therapeutic areas for which unsatisfied therapeutic needs persist. For example, high unmet clinical need was observed in patients diagnosed with type 2 diabetes mellitus and hemophilia, as well as in specific age groups, such as the pediatric population. Given the urgent need to improve the therapy of clinical conditions for which unmet clinical need is established, clinical testing, and approval of new medicines are increasingly being carried out through accelerated authorization procedures. Read More

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https://www.frontiersin.org/article/10.3389/fphar.2019.00111
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http://dx.doi.org/10.3389/fphar.2019.00111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381027PMC
February 2019
8 Reads

[A case of spinal and bulbar muscular atrophy with improved walking ability following gait training using the hybrid assistive limb (HAL)].

Rinsho Shinkeigaku 2019 Mar 28;59(3):157-159. Epub 2019 Feb 28.

Department of Neurology, Ichinomiya-Nishi Hospital.

A 64-year-old man was diagnosed with spinal and bulbar muscular atrophy (SBMA) in 2014, and began gait training with the hybrid assistive limb (HAL) in 2017. We conducted 2 courses of HAL-based gait training and temporary improvement was confirmed both before and after intervention based on evaluation of the 2-minute walking distance, walking speed, and the Timed Up and Go test. HAL-based gait training may be effective for improving and maintaining walking ability in SBMA. Read More

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http://dx.doi.org/10.5692/clinicalneurol.cn-001223DOI Listing
March 2019
2 Reads

RESOLUTION OF SKIN NECROSIS AFTER NUSINERSEN TREATMENT IN AN INFANT WITH SPINAL MUSCULAR ATROPHY.

Muscle Nerve 2019 Feb 27. Epub 2019 Feb 27.

The NEMO Center in Milan, Neurorehabilitation Unit, University of Milan, ASST Niguarda Hospital, Milan, Italy.

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http://dx.doi.org/10.1002/mus.26457DOI Listing
February 2019
1 Read

Sensory modulation of fasciculation discharge frequency.

Muscle Nerve 2019 Feb 27. Epub 2019 Feb 27.

Instituto de Fisiologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal.

Introduction: Fasciculations are a marker for the diagnosis of amyotrophic lateral sclerosis (ALS) and reflect increased lower motor neuron (LMN) excitability.

Methods: We investigated modulation of fasciculation frequency in the first dorsal interosseous (FDI) muscle of the right hand following peripheral sensory nerve electrical stimulation, and vibration over the muscle-tendon region (50 and 100 Hz), in patients with ALS, spinal muscular atrophy, and benign fasciculation syndrome. FDI muscles of ALS patients were classified by the presence or absence of neurogenic changes on needle electromyography. Read More

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http://doi.wiley.com/10.1002/mus.26456
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http://dx.doi.org/10.1002/mus.26456DOI Listing
February 2019
20 Reads