Search

Your search keyword '"Association Institut de Myologie [Paris]"' showing total 8 results
Start Over Author "Association Institut de Myologie [Paris]"
8 results on '"Association Institut de Myologie [Paris]"'

1. DMPK hypermethylation in sperm cells of myotonic dystrophy type 1 patients

Author

Pauline Megalli, Talia Eldar-Geva, Rachel Eiges, Silvina Epsztejn-Litman, Gheona Altarescu, Oshrat Schonberger, Shira Yanovsky-Dagan, Eliora Cohen, The Hebrew University Hadassah Medical School, Shaare Zedek Medical Center [Jerusalem, Israel], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Centre de Recherche en Myologie, and Association Institut de Myologie [Paris]

Subjects
musculoskeletal diseases, Male, Untranslated region, Somatic cell, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, Myotonic dystrophy, Myotonin-Protein Kinase, Germline, Andrology, 03 medical and health sciences, 0302 clinical medicine, Semen, Genetics, medicine, Humans, Myotonic Dystrophy, Muscular dystrophy, Gene, Genetics (clinical), 030304 developmental biology, 0303 health sciences, DNA Methylation, medicine.disease, Spermatozoa, Sperm, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, DNA methylation, Trinucleotide Repeat Expansion, 030217 neurology & neurosurgery
Abstract

Myotonic dystrophy type 1 (DM1) is an autosomal dominant muscular dystrophy that results from a CTG expansion (50–4000 copies) in the 3′ UTR of the DMPK gene. The disease is classified into four or five somewhat overlapping forms, which incompletely correlate with expansion size in somatic cells of patients. With rare exception, it is affected mothers who transmit the congenital (CDM1) and most severe form of the disease. Why CDM1 is hardly ever transmitted by fathers remains unknown. One model to explain the almost exclusive transmission of CDM1 by affected mothers suggests a selection against hypermethylated large expansions in the germline of male patients. By assessing DNA methylation upstream to the CTG expansion in motile sperm cells of four DM1 patients, together with availability of human embryonic stem cell (hESCs) lines with paternally inherited hypermethylated expansions, we exclude the possibility that DMPK hypermethylation leads to selection against viable sperm cells (as indicated by motility) in DM1 patients.

Published
2021
Full Text
View/download PDF

2. Cardiovascular manifestations of myotonic dystrophy

Author

Denis Furling, Karim Wahbi, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM), Association Institut de Myologie [Paris], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Centre de Recherche en Myologie

Subjects
Pacemaker, Artificial, medicine.medical_specialty, Cardiac pacing, Ventricular Tachyarrhythmias, Electric Countershock, 030204 cardiovascular system & hematology, Cardiac mortality, Sudden death, Myotonic dystrophy, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, Internal medicine, Prevalence, medicine, Animals, Humans, Myotonic Dystrophy, Genetic Predisposition to Disease, In patient, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Cardiovascular mortality, business.industry, Cardiac Pacing, Artificial, Dystrophy, Arrhythmias, Cardiac, medicine.disease, Defibrillators, Implantable, 3. Good health, Death, Sudden, Cardiac, Treatment Outcome, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract

Patients with myotonic dystrophy, the most common neuromuscular dystrophy in adults, have a high prevalence of arrhythmic complications with increased cardiovascular mortality and high risk for sudden death. Sudden death prevention is central and relies on annual follow-up and prophylactic permanent pacing in patients with conduction defects on electrocardiogram and/or infrahisian blocks on electrophysiological study. Implantable cardiac defibrillator therapy may be indicated in patients with ventricular tachyarrhythmia.

Published
2020
Full Text
View/download PDF

3. Beyond the Traditional Clinical Trials for Amyotrophic Lateral Sclerosis and The Future Impact of Gene Therapy

Author

Cappella, Marisa, Pradat, Pierre-François, Querin, Giorgia, Biferi, Maria, Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Ulster, HAL-SU, Gestionnaire, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Association Institut de Myologie [Paris], and Centre de Recherche en Myologie

Subjects
Clinical Trials as Topic, clinical trials, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV]Life Sciences [q-bio], Amyotrophic Lateral Sclerosis, AAV, Review, Genetic Therapy, Oligonucleotides, Antisense, ASO, Gene therapy, shRNA, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ALS, antisense oligonucleotides, CNS, Intra-CSF delivery, MND, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, miRNA
Abstract

International audience; Amyotrophic lateral sclerosis (ALS) is a devastating and incurable motor neuron (MN) disorder affecting both upper and lower MNs. Despite impressive advances in the understanding of the disease’s pathological mechanism, classical pharmacological clinical trials failed to provide an efficient cure for ALS over the past twenty years. Two different gene therapy approaches were recently approved for the monogenic disease Spinal muscular atrophy, characterized by degeneration of lower MNs. This milestone suggests that gene therapy-based therapeutic solutions could be effective for the treatment of ALS. This review summarizes the possible reasons for the failure of traditional clinical trials for ALS. It provides then a focus on the advent of gene therapy approaches for hereditary forms of ALS. Specifically, it describes clinical use of antisense oligonucleotides in three familial forms of ALS, caused by mutations in SOD1, C9orf72 and FUS genes, respectively.. Clinical and pre-clinical studies based on AAV-mediated gene therapy approaches for both familial and sporadic ALS cases are presented as well. Overall, this overview highlights the potential of gene therapy as a transforming technology that will have a huge impact on treatment perspective for ALS patients and on the design of future clinical trials.

Published
2021
Full Text
View/download PDF

4. FISH protocol for Myotonic Dystrophy type 1 cells

Author

Klein, Arnaud F., Arandel, Ludovic, Marie, Joëlle, Furling, Denis, Furling, Denis, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM), Association Institut de Myologie [Paris], and Centre de Recherche en Myologie

Subjects
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019
Full Text
View/download PDF

5. Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice

Author

Miguel A. Varela, Naira Naouar, David Seoane, Arnaud F. Klein, A Arzumanov, Jack Puymirat, Ashling Holland, Denis Furling, Michael J. Gait, Geneviève Gourdon, Matthew J.A. Wood, Guillaume Bassez, Arnaud Ferry, Lucile Revillod, Ludovic Arandel, Dominic Jauvin, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Généthon, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Association Institut de Myologie [Paris], University of Oxford [Oxford], Université Sorbonne Paris Cité (USPC), Centre de recherche du CHU de Québec-Université Laval (CRCHUQ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Medical Research Council Laboratory of Molecular Biology, Cambridge, Centre de Recherche en Myologie, Gourdon, Geneviève, University of Oxford, Centre de référence des maladies rares neuromusculaires [CHU Pitié-Salpétriêre], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), SLAC National Accelerator Laboratory (SLAC), and Stanford University

Subjects
0301 basic medicine, musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Morpholino, Myotonic dystrophy, 03 medical and health sciences, Splicing factor, chemistry.chemical_compound, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Myocyte, MBNL1, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, RNA, Skeletal muscle, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Medicine, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, RNA splicing, Cancer research, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Antisense oligonucleotides (ASOs) targeting pathologic RNAs have shown promising therapeutic corrections for many genetic diseases including myotonic dystrophy (DM1). Thus, ASO strategies for DM1 can abolish the toxic RNA gain-of-function mechanism caused by nucleus-retained mutant DMPK (DM1 protein kinase) transcripts containing CUG expansions (CUGexps). However, systemic use of ASOs for this muscular disease remains challenging due to poor drug distribution to skeletal muscle. To overcome this limitation, we test an arginine-rich Pip6a cell-penetrating peptide and show that Pip6a-conjugated morpholino phosphorodiamidate oligomer (PMO) dramatically enhanced ASO delivery into striated muscles of DM1 mice following systemic administration in comparison with unconjugated PMO and other ASO strategies. Thus, low-dose treatment with Pip6a-PMO-CAG targeting pathologic expansions is sufficient to reverse both splicing defects and myotonia in DM1 mice and normalizes the overall disease transcriptome. Moreover, treated DM1 patient-derived muscle cells showed that Pip6a-PMO-CAG specifically targets mutant CUGexp-DMPK transcripts to abrogate the detrimental sequestration of MBNL1 splicing factor by nuclear RNA foci and consequently MBNL1 functional loss, responsible for splicing defects and muscle dysfunction. Our results demonstrate that Pip6a-PMO-CAG induces long-lasting correction with high efficacy of DM1-associated phenotypes at both molecular and functional levels, and strongly support the use of advanced peptide conjugates for systemic corrective therapy in DM1.

Published
2019
Full Text
View/download PDF

6. FISH Protocol for Myotonic Dystrophy Type 1 Cells.

Author

Klein AF, Arandel L, Marie J, and Furling D

Subjects
Cell Nucleus genetics, Cells, Cultured, Fluorescent Antibody Technique, Humans, Mutation, Single Molecule Imaging, Trinucleotide Repeat Expansion, In Situ Hybridization, Fluorescence methods, Myotonic Dystrophy genetics, Myotonin-Protein Kinase genetics, RNA-Binding Proteins genetics
Abstract

Mutant DMPK transcripts containing expanded CUG repeats (CUGexp) are retained within the nucleus of myotonic dystrophy type 1 (DM1) cells as discrete foci. Nuclear CUGexp-RNA foci that sequester MBNL1 splicing factor represent a hallmark of this RNA dominant disease caused by the expression of expanded microsatellite repeats. Here we described fluorescent in situ hybridization (FISH) techniques to detect either RNA containing CUG expansion or DMPK transcripts in human DM1 or WT cells. In addition, we propose a combined FISH/immunofluorescence protocol to visualize the colocalization of MBNL1 with CUGexp-RNA foci in DM1 cells.

Published
2020
Full Text
View/download PDF

7. Upper limb evaluation and one-year follow up of non-ambulant patients with spinal muscular atrophy: an observational multicenter trial.

Author

Seferian AM, Moraux A, Canal A, Decostre V, Diebate O, Le Moing AG, Gidaro T, Deconinck N, Van Parys F, Vereecke W, Wittevrongel S, Annoussamy M, Mayer M, Maincent K, Cuisset JM, Tiffreau V, Denis S, Jousten V, Quijano-Roy S, Voit T, Hogrel JY, and Servais L

Subjects
Adolescent, Adult, Child, Female, Follow-Up Studies, Hand Strength physiology, Humans, Male, Noninvasive Ventilation, Pinch Strength physiology, Spinal Muscular Atrophies of Childhood physiopathology, Young Adult, Muscular Atrophy, Spinal physiopathology, Upper Extremity physiopathology
Abstract

Assessment of the upper limb strength in non-ambulant neuromuscular patients remains challenging. Although potential outcome measures have been reported, longitudinal data demonstrating sensitivity to clinical evolution in spinal muscular atrophy patients are critically lacking. Our study recruited 23 non-ambulant patients, 16 patients (males/females = 6/10; median age 15.4 years with a range from 10.7 to 31.1 years) with spinal muscular atrophy type II and 7 patients (males/females = 2/5; median age 19.9 years with a range from 8.3 to 29.9 years) with type III. The Brooke functional score was on median 3 with a range from 2 to 6. The average total vital capacity was 46%, and seven patients required non-invasive ventilation at night. Patients were assessed at baseline, 6 months, and 1 year using the Motor Function Measure and innovative devices MyoGrip, MyoPinch, and MoviPlate, which assess handgrip strength, key pinch strength, and hand/finger extension-flexion function, respectively. The study demonstrated the feasibility and reliability of these measures for all patients, and sensitivity to negative changes after the age of 14 years. The younger patients showed an increase of the distal force in the follow-up period. The distal force measurements and function were correlated to different functional scales. These data represent an important step in the process of validating these devices as potential outcome measures for future clinical trials.

Published
2015
Full Text
View/download PDF

8. Upper limb strength and function changes during a one-year follow-up in non-ambulant patients with Duchenne Muscular Dystrophy: an observational multicenter trial.

Author

Seferian AM, Moraux A, Annoussamy M, Canal A, Decostre V, Diebate O, Le Moing AG, Gidaro T, Deconinck N, Van Parys F, Vereecke W, Wittevrongel S, Mayer M, Maincent K, Desguerre I, Thémar-Noël C, Cuisset JM, Tiffreau V, Denis S, Jousten V, Quijano-Roy S, Voit T, Hogrel JY, and Servais L

Subjects
Adolescent, Adult, Child, Female, Follow-Up Studies, Humans, Male, Muscular Dystrophy, Duchenne drug therapy, Young Adult, Muscle Strength drug effects, Muscular Dystrophy, Duchenne physiopathology, Recovery of Function drug effects, Upper Extremity physiopathology
Abstract

Introduction: Upper limb evaluation of patients with Duchenne Muscular Dystrophy is crucially important to evaluations of efficacy of new treatments in non-ambulant patients. In patients who have lost ambulation, there are few validated and informative outcome measures. In addition, longitudinal data demonstrating sensitivity to clinical evolution of outcome measures over short-term periods are lacking., Patients and Methods: We report here the results of a one-year multicenter study using specifically designed tools to assess grip, pinch strength, and hand function in wheelchair-bound patients. Our study assessed 53 non-ambulant patients with Duchenne muscular dystrophy aged 17.1 ± 4.8 years (range: 9 - 28.1 years). The average Brooke functional score of these patients was 4.6 ± 1.1. The average forced vital capacity was 44.5% predicted and 19 patients used non-invasive ventilation. Patients were assessed at baseline, 6 months, and one year using the Motor Function Measure and innovative devices (namely the MyoSet composed of MyoGrip, MyoPinch, and MoviPlate)., Results: Our study confirmed preliminary data previously reported regarding feasibility of use and of reliability of the MyoSet and the correlation at baseline between distal strength and clinical outcomes such as FVC, Brooke score, age, and duration since loss of ambulation. A significant correlation was observed between the distal upper limb strength and clinical variables. The sensitive dynamometers (MyoGrip and MyoPinch) and MoviPlate captured a 12-month change in non-ambulant Duchenne muscular dystrophy patients of all ages., Trial Registration: ClinicalTrials.gov NCT00993161 NCT00993161.

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results