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Rev Med Liege 2019 Feb;74(2):82-85

Service de Pédiatrie, Centre de Références des Maladies Neuromusculaires, CHU Liège, Belgique.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder. The infantile form is the most common genetic cause of infantile death due to respiratory insufficiency. The disorder is caused by the premature death of motor neurons of anterior horn, leading to progressive weakness and muscular atrophy. Read More

Front Cell Neurosci 2019 7;13:15. Epub 2019 Feb 7.

Delaware Center for Neuroscience Research, Delaware State University, Dover, DE, United States.

Spinal muscular atrophy (SMA) is the leading genetic cause of death in infants. Studies with mouse models have demonstrated increased excitability and loss of afferent proprioceptive synapses on motor neurons (MNs). To further understand functional changes in the motor neural network occurring in SMA, we studied the intrinsic excitability and synaptic transmission of both MNs and interneurons (INs) from ventral horn in the lumbar spinal cord in the survival motor neuron (SMN)Δ7 mouse model. Read More

Hum Genet 2019 Feb 20. Epub 2019 Feb 20.

Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH, USA.

Spinal muscular atrophy (SMA) is a progressive motor neuron disease caused by loss or mutation of the survival motor neuron 1 (SMN1) gene and retention of SMN2. We performed targeted capture and sequencing of the SMN2, CFTR, and PLS3 genes in 217 SMA patients. We identified a 6. Read More

Neurology 2019 Feb 20. Epub 2019 Feb 20.

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Objective: To determine whether blood biomarkers of neuronal damage (neurofilament light chain [NfL]), muscle damage (creatine kinase [CK]), and muscle mass (creatinine) are altered in spinal bulbar muscular atrophy (SBMA) and can be used as biomarkers for disease severity.

Methods: In this multicenter longitudinal prospective study, plasma and serum were collected from 2 cohorts of patients with SBMA in London, United Kingdom (n = 50), and Padova, Italy (n = 43), along with disease (amyotrophic lateral sclerosis [ALS]) and healthy controls, and levels of plasma and serum NfL, CK, and creatinine were measured. Disease severity was assessed by the SBMA Functional Rating Scale and the Adult Myopathy Assessment Tool at baseline and 12 and 24 months. Read More

J Manag Care Spec Pharm 2019 Feb 20:1-7. Epub 2019 Feb 20.

3 Independent Consultant, Libertyville, Illinois.

While one-time gene replacement therapies may offer transformative innovation for the management of ultrarare, health-catastrophic diseases, they also pose challenges to the current U.S. health care system. Read More

J Vis Exp 2019 Jan 30(143). Epub 2019 Jan 30.

Calibr, The Scripps Research Institute;

In the process of drug development of RNA-targeting small molecules, elucidating the structural changes upon their interactions with target RNA sequences is desired. We herein provide a detailed in vitro and in-cell selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) protocol to study the RNA structural change in the presence of an experimental drug for spinal muscular atrophy (SMA), survival of motor neuron (SMN)-C2, and in exon 7 of the pre-mRNA of the SMN2 gene. In in vitro SHAPE, an RNA sequence of 140 nucleotides containing SMN2 exon 7 is transcribed by T7 RNA polymerase, folded in the presence of SMN-C2, and subsequently modified by a mild 2'-OH acylation reagent, 2-methylnicotinic acid imidazolide (NAI). Read More

Genet Med 2019 Feb 18. Epub 2019 Feb 18.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Purpose: To consider the impact and cost-effectiveness of offering preventive population genomic screening to all young adults in a single-payer health-care system.

Methods: We modeled screening of 2,688,192 individuals, all adults aged 18-25 years in Australia, for pathogenic variants in BRCA1/BRCA2/MLH1/MSH2 genes, and carrier screening for cystic fibrosis (CF), spinal muscular atrophy (SMA), and fragile X syndrome (FXS), at 71% testing uptake using per-test costs ranging from AUD$200 to $1200 (~USD$140 to $850). Investment costs included genetic counseling, surveillance, and interventions (reimbursed only) for at-risk individuals/couples. Read More

J Hum Genet 2019 Feb 15. Epub 2019 Feb 15.

United Diagnostic and Research Center for Clinical Genetics, School of Public Health of Xiamen University & Xiamen Maternal and Child Health Hospital, 361003, Xiamen, Fujian, China.

Carrier screening of spinal muscular atrophy (SMA) can provide reproductive options for carriers and prevent the birth defects. Here, we developed a simple screening test based on melting analysis. The test comprises a duplex PCR with two primer pairs and three probes to simultaneous amplify SMN1, SMN2, and CFTR. Read More

Neural Regen Res 2019 Jun;14(6):931-938

Department of Hand Surgery, the Second Hospital of Jilin University, Changchun, Jilin Province, China.

Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. Read More

Genet Med 2019 Feb 14. Epub 2019 Feb 14.

Myriad Women's Health (formerly Counsyl), South San Francisco, CA, USA.

Purpose: Carrier screening identifies couples at high risk for conceiving offspring affected with serious heritable conditions. Minimal guidelines recommend offering testing for cystic fibrosis and spinal muscular atrophy, but expanded carrier screening (ECS) assesses hundreds of conditions simultaneously. Although medical societies consider ECS an acceptable practice, the health economics of ECS remain incompletely characterized. Read More

Autophagy 2019 Feb 11:1-20. Epub 2019 Feb 11.

a Program in Developmental Biology , Baylor College of Medicine , Houston , TX , USA.

Mutations in the ER-associated VAPB/ALS8 protein cause amyotrophic lateral sclerosis and spinal muscular atrophy. Previous studies have argued that ER stress may underlie the demise of neurons. We find that loss of VAP proteins (VAPs) leads to an accumulation of aberrant lysosomes and impairs lysosomal degradation. Read More

Clin Neuropathol 2019 Feb 10. Epub 2019 Feb 10.

Heterozygous variants in the bicaudal D homolog 2 gene () are associated with autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED2). This disease is usually characterized by congenital or early-onset muscle weakness and atrophy of the lower extremities with benign or slow progression. We herein described an autosomal dominant inherited pedigree with SMALED2 in which the affected individuals presented with late adult-onset muscle weakness and wasting in the lower extremities. Read More

BMC Neurol 2019 Feb 9;19(1):21. Epub 2019 Feb 9.

Child Development and Exercise Center, Wilhelmina Children's Hospital, University Medical Center Utrecht, PO Box 85090, KB 02.056.0, 3508, AB, Utrecht, The Netherlands.

Background: Fatigability has emerged as an important dimension of physical impairment in patients with Spinal Muscular Atrophy (SMA). At present reliable and valid outcome measures for both mildly and severely affected patients are lacking. Therefore the primary aim of this study is the development of clinical outcome measures for fatigability in patients with SMA across the range of severity. Read More

Sci Rep 2019 Feb 7;9(1):1633. Epub 2019 Feb 7.

Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder that causes progressive muscle weakness and is the leading genetic cause of infant mortality worldwide. SMA is caused by the loss of survival motor neuron 1 (SMN1). In humans, a nearly identical copy gene is present, called SMN2. Read More

BMC Musculoskelet Disord 2019 Feb 7;20(1):54. Epub 2019 Feb 7.

Faculty of Rehabilitation, Józef Piłsudski University of Physical Education, Marymoncka 34, 00-968, Warsaw, Poland.

Background: The majority of individuals with spinal muscular atrophy (SMA) experience progressive skeletal deformities which may affect the quality of life and mobility. To date, no studies have evaluated the reliability of tests assessing body posture and joint mobility in SMA patients. The purpose of this study was to assess the reliability of Cervical Rotation test (CR), Supine Angle of Trunk Rotation test (SATR), Hip Extension test (HE) and Pelvic Obliquity test (PO) developed to evaluate the musculoskeletal system in SMA individuals. Read More

Rev Chil Pediatr 2018 Dec;89(6):685-693

Programa Trastornos Motores y Enfermedades Neuromusculares, Clínica Las Condes, Chile.

Spinal muscular atrophy (SMA) is the first inherited cause of mortality in infants, with four subtypes: SMA0 prenatal onset, SMA1 babies less than 3 months non sitters, SMA2 sitters and SMA3 walkers. Pneumonia and respiratory insufficiency are the most severe complications. Informed parental de cisions are relevant. Read More

Neuroreport 2019 Feb 4. Epub 2019 Feb 4.

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

Survival motor neuron (SMN) deficiency indicates that various cellular processes are impaired in spinal muscular atrophy (SMA). Previous reports have shown that SMN deficiency causes motor neuron degeneration, whereas the numbers of astrocytes and microglia are significantly increased or activated in SMA model systems. Only a few groups have studied the role of oligodendrocyte (OL) lineages such as OL precursor cell and nerve/glial antigen 2 (NG2)-glia in SMA pathology. Read More

Chronic Obstr Pulm Dis 2018 Sep 15;5(4):258-266. Epub 2018 Sep 15.

Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts.

PIZZ alpha-1 antitrypsin deficiency (AATD) is an autosomal recessive disease affecting approximately 100,000 individuals in the United States and one of the most common hereditary causes of liver disease. The most common form of the disease results from a single base pair mutation (Glu342Lys), known as the "Z" mutation, that encodes a mutant protein (Z alpha-1 antritypsin [AAT]) that is prone to misfolding and is retained in the endoplasmic reticulum (ER) rather than appropriately secreted. Some of the retained mutant protein attains an unusual aggregated or conformation. Read More

Discov Med 2019 01;27(146):37-43

Severn Health Solutions, Severna Park, MD 21146, USA.

NSAIDs may prevent Alzheimer's disease (AD) but have failed as a treatment, possibly because only 1-2% of an oral NSAID dose reaches the brain. This minuscule dose is enough to have a preventative effect on Alzheimer's disease but not to treat it. We propose a new route of administration for drugs to treat AD: transspinal delivery by transdermal patch over the back-of-neck/cervical spine. Read More

Pharmacoeconomics 2019 Feb 4. Epub 2019 Feb 4.

Acaster Lloyd Consulting Ltd, London, UK.

Background: Spinal muscular atrophy is a rare neuromuscular disorder with a spectrum of severity related to age at onset and the number of SMN2 gene copies. Infantile-onset (≤ 6 months of age) is the most severe spinal muscular atrophy and is the leading monogenetic cause of infant mortality; patients with later-onset (> 6 months of age) spinal muscular atrophy can survive into adulthood. Nusinersen is a new treatment for spinal muscular atrophy. Read More

Disabil Rehabil 2019 Jan 29:1-9. Epub 2019 Jan 29.

a Department of Rehabilitation, Physical Therapy Science & Sports, Brain Center Rudolf Magnus , University Medical Centre Utrecht , Utrecht , The Netherlands.

Purpose: Patients with spinal muscular atrophy (SMA) suffer from slowly progressive weakness of axial, respiratory and proximal muscles, leading to restrictions in activity and participation. This study aims to investigate patients' level of psychological well-being, using the International Classification of Functioning model and self-determination theory as theoretical frameworks.

Materials And Methods: In this cross-sectional study, adults with SMA were invited to complete a questionnaire. Read More

Muscle Nerve 2019 Jan 24. Epub 2019 Jan 24.

Paediatric Neurology and Centro Clinico Nemo, Catholic University and Policlinico Gemelli, Fondazione Policlinico Universitario Agostino Gemelli IRCSS, Rome, Italy.

Introduction: The aim of the study was to assess 12 month changes in upper limb function in patients affected by spinal muscular atrophy type 2 and 3.

Methods: Longitudinal 12 month data was collected in 114 patients, 60 type 2 and 54 type 3, using the Revised Upper Limb Module.

Results: The 12 month changes ranged between -7 and 9 (mean: -0. Read More

Amyotroph Lateral Scler Frontotemporal Degener 2019 Jan 22:1-8. Epub 2019 Jan 22.

j Department of Physiology , University of Valencia , Valencia , Spain.

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by progressive loss of spinal and cortical motor neurons, leading to muscular atrophy, respiratory failure, and ultimately death. There is no known cure, and the clinical benefit of the two drugs approved to treat ALS remains unclear. Novel disease-modifying therapeutics that are able to modulate the disease course are desperately needed. Read More

Stem Cells Dev 2019 Feb 20. Epub 2019 Feb 20.

1 Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.

Spinal muscular atrophy (SMA) is caused by the mutation or deletion of the survival motor neuron 1 (SMN1) gene. Only ∼10% of the products of SMN2, a paralogue of SMN1, are functional full-length SMN (SMN-FL) proteins, whereas SMN2 primarily produces alternatively spliced transcripts lacking exon 7. Reduced SMN protein levels in SMA patients lead to progressive degeneration of spinal motor neurons (MNs). Read More

Orphanet J Rare Dis 2019 Jan 21;14(1):18. Epub 2019 Jan 21.

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

Background: Survival and quality of life for patients affected by spinal muscular atrophy (SMA) are thought to have improved over the last decade due to changes in care. In addition, targeted treatments for SMA have been developed based on a better understanding of the molecular pathology. In 2016 and 2017, nusinersen was the first drug to be approved for treatment of all types of SMA in the United States and in Europe based on well-controlled clinical trials in a small subgroup of pediatric SMA patients. Read More

J Vis Exp 2019 Jan 7(143). Epub 2019 Jan 7.

Institut NeuroMyoGène, CNRS UMR5310, INSERM U1217, Université Lyon; Centre de Biotechnologie Cellulaire, Hospices Civils de Lyon.

Neurodegeneration of spinal motoneurons (MNs) is implicated in a large spectrum of neurological disorders including amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, and spinal muscular atrophy, which are all associated with muscular atrophy. Primary cultures of spinal MNs have been used widely to demonstrate the involvement of specific genes in such diseases and characterize the cellular consequences of their mutations. This protocol models a primary MN culture derived from the seminal work of Henderson and colleagues more than twenty years ago. Read More

Stem Cell Res 2019 Jan 11;34:101376. Epub 2019 Jan 11.

Federal Research Center Institute of Cytology and Genetics, Novosibirsk, Russia; Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia; E.N. Meshalkin National Medical Research Centre, Ministry of Healthcare of Russian Federation, Novosibirsk, Russia; National Research University Novosibirsk State University, Novosibirsk, Russia. Electronic address:

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletion or mutation in SMN1 gene. SMA human induced pluripotent stem cells (iPSCs) represent a useful and valid model for the study of the disorder, as they provide in vitro the target cells. We generated iPSCs from a SMA type I patient and SMA type II patient by using non-integrating episomal plasmid vectors. Read More

Ann Clin Transl Neurol 2019 Jan 13;6(1):197-205. Epub 2018 Nov 13.

Division of Child Neurology and Metabolic Medicine Center for Child and Adolescent Medicine University Hospital Heidelberg Heidelberg Germany.

In recent years, disease-modifying and life-prolonging therapies for spinal muscular atrophy (SMA) have been developed. However, patients are currently diagnosed with significant delay and therapies are often administered in advanced stages of motor neuron degeneration, showing limited effects. Methods to identify children in presymptomatic stages are currently evaluated in newborn screening programs. Read More

Neurospine 2019 01 4. Epub 2019 Jan 4.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Hirayama disease, a juvenile muscular atrophy of the distal upper extremity, is a rare form of cervical flexion myelopathy characterized by insidiously progressive weakness of the hands and forearm muscles (i.e. painless amyotrophy). Read More

J Clin Imaging Sci 2018 6;8:53. Epub 2018 Dec 6.

Department of Radiology, Advocate Illinois Masonic Medical Center, Chicago, Illinois, USA.

Motor neuron diseases (MNDs) are a debilitating subset of diseases, which result in progressive neuronal destruction and eventual loss of voluntary muscular function. These entities are often challenging to distinguish and accurately diagnose given overlapping clinical pictures and overall rarity. This group of diseases has a high morbidity and mortality rate overall and delineating each type of disease can help guide appropriate clinical management and improve quality of life for patients. Read More

Brain 2019 Feb;142(2):276-294

Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Italy.

Spinal muscular atrophy is a motor neuron disorder caused by mutations in SMN1. The reasons for the selective vulnerability of motor neurons linked to SMN (encoded by SMN1) reduction remain unclear. Therefore, we performed deep RNA sequencing on human spinal muscular atrophy motor neurons to detect specific altered gene splicing/expression and to identify the presence of a common sequence motif in these genes. Read More

Eur J Clin Nutr 2019 Jan 15. Epub 2019 Jan 15.

International Center for the Assessment of Nutritional Status (ICANS), Department of Food Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy.

Spinal muscular atrophy (SMA) is a neuromuscular disease associated with nutritional status derangement and altered body composition. New drugs are changing the natural history of the disease, so now more than ever is important to focus on the correct assessment of nutritional status in SMA. We implemented a standardization process for the anthropometric measurement as part of our ongoing longitudinal study of growth patterns in SMA patients. Read More

Sci Rep 2019 Jan 15;9(1):119. Epub 2019 Jan 15.

Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, 19107, USA.

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by polyglutamine (polyQ) expansion in the androgen receptor (AR). Prior studies have highlighted the importance of AR nuclear localization in SBMA pathogenesis; therefore, in this study, we sought to determine the role of AR nuclear export in the pathological manifestations of SBMA. We demonstrate here that the nuclear export of polyQ-expanded AR is impaired, even prior to the formation of intranuclear inclusions of aggregated AR. Read More

J Child Neurol 2019 Jan 15:883073818822900. Epub 2019 Jan 15.

2 Ersta Sköndal Bräcke University College, Department of Health Care Sciences, Palliative Research Centre, Stockholm, Sweden.

Objective:: This study aims to assess the experiences and wishes of parents of children with severe spinal muscular atrophy regarding information and decision-making throughout the course of the illness.

Study Design:: A full population survey, conducted in 2015, among parents of children with severe spinal muscular atrophy who were born in Denmark between January 1, 2003, and December 31, 2013. We used a study-specific questionnaire with items about experiences and wishes concerning the provision of information about diagnosis, treatment, and end-of-life care. Read More

J Palliat Med 2019 Jan;22(1):109-111

1 Department of Palliative Care and Advanced Home Health Care, Primary Health Care Skåne, Lund, Sweden.

Intraosseous (IO) access is normally reserved for emergencies and critical care conditions when venous cannulation is not possible. Nonetheless, we present a case of IO insertion to a 56-year-old man, tetraplegic for many years due to progressive spinal muscular atrophy and with refractory suffering. The IO access was used for palliative sedation with propofol in a home care setting. Read More

Neural Regen Res 2019 Apr;14(4):699-705

Peking University People's Hospital, Beijing, China.

Our previous studies have confirmed that during nerve transposition repair to injured peripheral nerves, the regenerated nerve fibers of motor neurons in the anterior horn of the spinal cord can effectively repair distal nerve and target muscle tissue and restore muscle motor function. To observe the effect of nerve regeneration and motor function recovery after several types of nerve transposition for median nerve defect (2 mm), 30 Sprague-Dawley rats were randomly divided into sham operation group, epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group. Three months after nerve repair, the wrist flexion test was used to evaluate the recovery of wrist flexion after regeneration of median nerve in the affected limbs of rats. Read More

eNeuro 2018 Nov-Dec;5(6). Epub 2019 Jan 2.

Department of Pediatrics, Division of Neurology, Research Institute, Children's Hospital of Philadelphia, Philadelphia, PA 19104.

Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by degeneration of spinal motor neurons resulting in variable degrees of muscular wasting and weakness. It is caused by a loss-of-function mutation in the survival motor neuron () gene. mutants lacking recapitulate several aspects of the disease including impaired movement and shorted life span. Read More

Ugeskr Laeger 2019 Jan;181(2)

Spinal muscular atrophy (SMA) is an autosomal recessive disorder, which causes degeneration of peripheral nerves and muscles. It usually presents in childhood due to an insufficient level of survival motor neuron protein. This is a case series of three children, who had SMA type 1 or 2 and were treated with nusinersen from the age of five months, 16 months, and five years, respectively. Read More

Nervenarzt 2019 Jan 7. Epub 2019 Jan 7.

Klinik für Neuropädiatrie und Muskelerkrankungen, Medizinische Fakultät, Universitätsklinikum Freiburg, Freiburg, Deutschland.

Spinal muscular atrophy (SMA) is a progressive autosomal recessive neurodegenerative disease with an incidence of 1:10,000 live births. With a deeper understanding of the molecular basis of SMA in the past two decades, a major focus of therapeutic development has been on increasing the proportion of functionally capable 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. Since June 2017, the antisense oligonucleotide nusinersen/Spinraza® (Biogen GmbH, Ismaning, Germany) has been approved for 5qSMA treatment. Read More

J Hum Genet 2019 Mar 7;64(3):215-219. Epub 2019 Jan 7.

Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Distal spinal muscular atrophy (dSMA) is a rare clinically and genetically heterogeneous group of inherited disorders characterized by progressive distal muscle weakness and wasting. So far, more than 65% of patients with dSMA have undiscovered genetic mutations. Recently, compound heterozygous mutations in the vaccinia-related kinase 1 (VRK1) gene have been identified for the first time in two siblings with adult-onset dSMA from an Ashkenazi Jewish family. Read More

Neuroscientist 2019 Jan 7:1073858418822993. Epub 2019 Jan 7.

2 Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.

Polyglutamine (polyQ) diseases are a group of hereditary neurodegenerative disorders caused by expansion of unstable polyQ repeats in their associated disease proteins. To date, the pathogenesis of each disease remains poorly understood, and there are no effective treatments. Growing evidence has indicated that, in addition to neurodegeneration, polyQ-expanded proteins can cause a wide array of abnormalities in peripheral tissues. Read More

JCO Precis Oncol 2018 29;2. Epub 2018 Jun 29.

Weill Cornell Medicine; Weill Cornell Medicine-New York Presbyterian Hospital, New York, NY.

N Engl J Med 2019 01;380(1):57-70

From Research and Development, Avidity Biosciences, La Jolla, CA.

Neuromuscul Disord 2018 Oct 31. Epub 2018 Oct 31.

Department of Neuropediatrics, Children's Hospital of the University of Toulouse, 330 Great Britain Avenue, TSA 70034 Toulouse, France.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive neuromuscular disorder characterized by progressive motor and respiratory decline during the first year of life. Early and late-onset cases have recently been reported, although not meeting the established diagnostic criteria, these cases have been genotyped. We thus conducted a national multicenter observational retrospective study to determine the prognosis of children with SMARD1 according to their phenotype. Read More

J Neuromuscul Dis 2019 ;6(1):119-131

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

Background: Spinal muscular atrophy (SMA) is a genetic disorder characterized by muscle loss. In December 2016 the FDA approved the first and only treatment drug for SMA: Spinraza (nusinersen). Despite excitement and optimism, there are no published data on the perceptions of individuals with SMA and their families about the benefits, risks, and challenges associated with treatment. Read More

J Med Genet 2018 Dec 28. Epub 2018 Dec 28.

Muscle Pathology and Neuroimmunology Unit, Neurological Institute Carlo Besta, Milano, Italy.

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder, due to the loss of function of the survival motor neuron () gene. The first treatment for the condition, recently approved, is based on the reduction of exon 7 skipping in mRNAs produced by a highly homologous gene (). The primary objective of the present study was to evaluate the applicability of the dosage of SMN gene produts in blood, as biomarker for SMA, and the safety of oral salbutamol, a beta2-adrenergic agonist modulating levels. Read More

Pediatr Neurol 2018 Nov 22. Epub 2018 Nov 22.

Division of Critical Care, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.

Spine Deform 2019 01;7(1):107-111

Pediatric Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.

Objective: The objective of this study is to identify preoperative laboratory values and patient factors that are associated with postoperative respiratory complications in pediatric neuromuscular scoliosis (NMS) populations undergoing posterior spinal fusion (PSF) with instrumentation.

Summary Of Background Data: PSF in NMS patients are high-risk surgeries. Respiratory complications are the most common postoperative event, with rates up to 28. Read More

Pediatrics 2019 Jan;143(1)

J Manag Care Spec Pharm 2018 Dec;24(12-a Suppl):S3-S16

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease that, in most cases, involves homozygous deletion of the SMN1 gene. This causes a deficiency in survival motor neuron (SMN) protein, which plays a critical role in motor neuron development. SMA has a range of phenotype expression resulting in variable age of symptom onset, maximum motor strength achieved, and survival. Read More