The Experts below are selected from a list of 22704 Experts worldwide ranked by ideXlab platform
Katja Grohmann - One of the best experts on this subject based on the ideXlab platform.
-
infantile spinal Muscular Atrophy with respiratory distress type 1 smard1
Annals of Neurology, 2003Co-Authors: Piroschka Stolz, Catrin Janetzki, Raymonda Varon, Katja Grohmann, Kate Bushby, Enrico Bertini, Francesco Muntoni, Markus Schuelke, Robert A OuvrierAbstract:Autosomal recessive spinal Muscular Atrophy with respiratory distress type 1 (SMARD1) is the second anterior horn cell disease in infants in which the genetic defect has been defined. SMARD1 results from mutations in the gene encoding the immunoglobulin mu-binding protein 2 (IGHMBP2) on chromosome 11q13. Our aim was to review the clinical features of 29 infants affected with SMARD1 and report on 26 novel IGHMBP2 mutations. Intrauterine growth retardation, weak cry, and foot deformities were the earliest symptoms of SMARD1. Most patients presented at the age of 1 to 6 months with respiratory distress due to diaphragmatic paralysis and progressive muscle weakness with predominantly distal lower limb muscle involvement. Sensory and autonomic nerves are also affected. Because of the poor prognosis, there is a demand for prenatal diagnosis, and clear diagnostic criteria for infantile SMARD1 are needed. The diagnosis of SMARD1 should be considered in infants with non-5q spinal Muscular Atrophy, neuropathy, and muscle weakness and/or respiratory distress of unclear cause. Furthermore, consanguineous parents of a child with sudden infant death syndrome should be examined for IGHMBP2 mutations.
-
severe spinal Muscular Atrophy variant associated with congenital bone fractures
Journal of Child Neurology, 2002Co-Authors: Ursula Felderhoffmueser, Katja Grohmann, Klaus Zerres, Anja Harder, Christine Stadelmann, Christoph Buhrer, Michael ObladenAbstract:Infantile autosomal recessive spinal Muscular Atrophy (type I) represents a lethal disorder leading to progressive symmetric Muscular Atrophy of limb and trunk muscles. Ninety-six percent cases of spinal Muscular Atrophy type I are caused by deletions or mutations in the survival motoneuron gene (SMN1) on chromosome 5q11.2-13.3. However, a number of chromosome 5q-negative patients with additional clinical features (respiratory distress, cerebellar hypoplasia) have been designated in the literature as infantile spinal Muscular Atrophy plus forms. In addition, the combination of severe spinal Muscular Atrophy and neurogenic arthrogryposis has been described. We present clinical, molecular, and autopsy findings of a newborn boy presenting with generalized Muscular Atrophy in combination with congenital bone fractures and extremely thin ribs but without contractures. (J Child Neurol 2002;17:718-721).
Eduardo F Tizzano - One of the best experts on this subject based on the ideXlab platform.
-
Neurofilament as a potential biomarker for spinal Muscular Atrophy
'Wiley', 2019Co-Authors: Basil T Darras, Thomas O Crawford, Eugenio Mercuri, Francesco Muntoni, Richard S. Finkel, Maryam Oskoui, Darryl C De Vivo, Eduardo F Tizzano, Monique M. Ryan, Guolin ZhaoAbstract:Abstract Objective To evaluate plasma phosphorylated neurofilament heavy chain (pNF‐H) as a biomarker in spinal Muscular Atrophy (SMA). Methods Levels of pNF‐H were measured using the ProteinSimple® platform in plasma samples from infants with SMA enrolled in ENDEAR (NCT02193074) and infants/children without neurological disease. Results Median pNF‐H plasma level was 167.0 pg/mL (7.46–7,030; n = 34) in children without SMA (aged 7 weeks–18 years) and was higher in those aged
-
nusinersen versus sham control in infantile onset spinal Muscular Atrophy
The New England Journal of Medicine, 2017Co-Authors: Richard S. Finkel, Eugenio Mercuri, Claudia A. Chiriboga, Basil T Darras, Laurent Servais, Anne M Connolly, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Eduardo F TizzanoAbstract:BackgroundSpinal Muscular Atrophy is an autosomal recessive neuroMuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonu...
-
nusinersen versus sham control in infantile onset spinal Muscular Atrophy
The New England Journal of Medicine, 2017Co-Authors: Richard S. Finkel, Eugenio Mercuri, Claudia A. Chiriboga, Basil T Darras, Laurent Servais, Anne M Connolly, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Eduardo F TizzanoAbstract:BackgroundSpinal Muscular Atrophy is an autosomal recessive neuroMuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. MethodsWe conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal Muscular Atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used ...
Richard S. Finkel - One of the best experts on this subject based on the ideXlab platform.
-
Neurofilament as a potential biomarker for spinal Muscular Atrophy
'Wiley', 2019Co-Authors: Basil T Darras, Thomas O Crawford, Eugenio Mercuri, Francesco Muntoni, Richard S. Finkel, Maryam Oskoui, Darryl C De Vivo, Eduardo F Tizzano, Monique M. Ryan, Guolin ZhaoAbstract:Abstract Objective To evaluate plasma phosphorylated neurofilament heavy chain (pNF‐H) as a biomarker in spinal Muscular Atrophy (SMA). Methods Levels of pNF‐H were measured using the ProteinSimple® platform in plasma samples from infants with SMA enrolled in ENDEAR (NCT02193074) and infants/children without neurological disease. Results Median pNF‐H plasma level was 167.0 pg/mL (7.46–7,030; n = 34) in children without SMA (aged 7 weeks–18 years) and was higher in those aged
-
nusinersen versus sham control in infantile onset spinal Muscular Atrophy
The New England Journal of Medicine, 2017Co-Authors: Richard S. Finkel, Eugenio Mercuri, Claudia A. Chiriboga, Basil T Darras, Laurent Servais, Anne M Connolly, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Eduardo F TizzanoAbstract:BackgroundSpinal Muscular Atrophy is an autosomal recessive neuroMuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonu...
-
nusinersen versus sham control in infantile onset spinal Muscular Atrophy
The New England Journal of Medicine, 2017Co-Authors: Richard S. Finkel, Eugenio Mercuri, Claudia A. Chiriboga, Basil T Darras, Laurent Servais, Anne M Connolly, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Eduardo F TizzanoAbstract:BackgroundSpinal Muscular Atrophy is an autosomal recessive neuroMuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. MethodsWe conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal Muscular Atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used ...
-
observational study of spinal Muscular Atrophy type 2 and 3 functional outcomes over 1 year
JAMA Neurology, 2011Co-Authors: Petra Kaufmann, Richard S. Finkel, Maryam Oskoui, Basil T Darras, Douglas M. Sproule, Peter B Kang, Michael P Mcdermott, Andrei Constantinescu, Reghan A FoleyAbstract:Objective To characterize the short-term course of spinal Muscular Atrophy (SMA) in a genetically and clinically well-defined cohort of patients with SMA.
-
consensus statement for standard of care in spinal Muscular Atrophy
Journal of Child Neurology, 2007Co-Authors: Ching H Wang, Thomas O Crawford, Enrico Bertini, Richard S. Finkel, Mary K Schroth, Anita K Simonds, Brenda Wong, Annie Aloysius, Leslie Morrison, Anthony TrelaAbstract:Spinal Muscular Atrophy is a neurodegenerative disease that requires multidisciplinary medical care. Recent progress in the understanding of molecular pathogenesis of spinal Muscular Atrophy and advances in medical technology have not been matched by similar developments in the care for spinal Muscular Atrophy patients. Variations in medical practice coupled with differences in family resources and values have resulted in variable clinical outcomes that are likely to compromise valid measure of treatment effects during clinical trials. The International Standard of Care Committee for Spinal Muscular Atrophy was formed in 2005, with a goal of establishing practice guidelines for clinical care of these patients. The 12 core committee members worked with more than 60 spinal Muscular Atrophy experts in the field through conference calls, e-mail communications, a Delphi survey, and 2 in-person meetings to achieve consensus on 5 care areas: diagnostic/new interventions, pulmonary, gastrointestinal/nutrition, orthopedics/rehabilitation, and palliative care. Consensus was achieved on several topics related to common medical problems in spinal Muscular Atrophy, diagnostic strategies, recommendations for assessment and monitoring, and therapeutic interventions in each care area. A consensus statement was drafted to address the 5 care areas according to 3 functional levels of the patients: nonsitter, sitter, and walker. The committee also identified several medical practices lacking consensus and warranting further investigation. It is the authors' intention that this document be used as a guideline, not as a practice standard for their care. A practice standard for spinal Muscular Atrophy is urgently needed to help with the multidisciplinary care of these patients.
Claudia A. Chiriboga - One of the best experts on this subject based on the ideXlab platform.
-
nusinersen versus sham control in infantile onset spinal Muscular Atrophy
The New England Journal of Medicine, 2017Co-Authors: Richard S. Finkel, Eugenio Mercuri, Claudia A. Chiriboga, Basil T Darras, Laurent Servais, Anne M Connolly, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Eduardo F TizzanoAbstract:BackgroundSpinal Muscular Atrophy is an autosomal recessive neuroMuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonu...
-
nusinersen versus sham control in infantile onset spinal Muscular Atrophy
The New England Journal of Medicine, 2017Co-Authors: Richard S. Finkel, Eugenio Mercuri, Claudia A. Chiriboga, Basil T Darras, Laurent Servais, Anne M Connolly, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Eduardo F TizzanoAbstract:BackgroundSpinal Muscular Atrophy is an autosomal recessive neuroMuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. MethodsWe conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal Muscular Atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used ...
-
nusinersen for the treatment of spinal Muscular Atrophy
Expert Review of Neurotherapeutics, 2017Co-Authors: Claudia A. ChiribogaAbstract:Introduction: Spinal Muscular Atrophy (SMA) is an autosomal recessive degenerative neuroMuscular disorder characterized by loss of spinal motor neurons leading to muscle weakness. This review artic...
Eugenio Mercuri - One of the best experts on this subject based on the ideXlab platform.
-
Neurofilament as a potential biomarker for spinal Muscular Atrophy
'Wiley', 2019Co-Authors: Basil T Darras, Thomas O Crawford, Eugenio Mercuri, Francesco Muntoni, Richard S. Finkel, Maryam Oskoui, Darryl C De Vivo, Eduardo F Tizzano, Monique M. Ryan, Guolin ZhaoAbstract:Abstract Objective To evaluate plasma phosphorylated neurofilament heavy chain (pNF‐H) as a biomarker in spinal Muscular Atrophy (SMA). Methods Levels of pNF‐H were measured using the ProteinSimple® platform in plasma samples from infants with SMA enrolled in ENDEAR (NCT02193074) and infants/children without neurological disease. Results Median pNF‐H plasma level was 167.0 pg/mL (7.46–7,030; n = 34) in children without SMA (aged 7 weeks–18 years) and was higher in those aged
-
nusinersen versus sham control in infantile onset spinal Muscular Atrophy
The New England Journal of Medicine, 2017Co-Authors: Richard S. Finkel, Eugenio Mercuri, Claudia A. Chiriboga, Basil T Darras, Laurent Servais, Anne M Connolly, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Eduardo F TizzanoAbstract:BackgroundSpinal Muscular Atrophy is an autosomal recessive neuroMuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. MethodsWe conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal Muscular Atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used ...
-
nusinersen versus sham control in infantile onset spinal Muscular Atrophy
The New England Journal of Medicine, 2017Co-Authors: Richard S. Finkel, Eugenio Mercuri, Claudia A. Chiriboga, Basil T Darras, Laurent Servais, Anne M Connolly, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Eduardo F TizzanoAbstract:BackgroundSpinal Muscular Atrophy is an autosomal recessive neuroMuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonu...
-
Childhood spinal Muscular Atrophy: controversies and challenges
Lancet Neurology, 2012Co-Authors: Eugenio Mercuri, Enrico Bertini, Susan T. IannacconeAbstract:Summary Spinal Muscular Atrophy is an autosomal recessive disorder characterised by degeneration of motor neurons in the spinal cord and is caused by mutations of the survival of motor neuron 1 gene SMN1 . The severity of spinal Muscular Atrophy is highly variable and no cure is available at present. Consensus has been reached on several aspects of care, the availability of which can have a substantial effect on prognosis, but controversies remain. The development of standards of care for children with the disorder and the identification of promising treatment strategies have changed the natural history of spinal Muscular Atrophy, and the prospects are good for further improvements in function, quality of life, and survival. A long-term benefit for patients will be the development of effective interventions (such as antisense oligonucleotides), some of which are in clinical trials. The need to be prepared for clinical trials has been the impetus for a remarkable and unprecedented cooperation between clinicians, scientists, industry, government, and volunteer organisations on an international scale.
