The Experts below are selected from a list of 2787 Experts worldwide ranked by ideXlab platform
Gisèle Bonne - One of the best experts on this subject based on the ideXlab platform.
-
Targeting the histone demethylase LSD1 prevents cardiomyopathy in a mouse model of Laminopathy
Journal of Clinical Investigation, 2021Co-Authors: Anne-claire Guenantin, Gisèle Bonne, Imen Jebeniani, Julia Leschik, Erwan Watrin, Nicolas Vignier, Michel PuceatAbstract:LMNA mutations in patients are responsible for a dilated cardiomyopathy. Molecular mechanisms underlying the origin and development of the pathology are unknown. Herein, using mouse pluripotent embryonic stem cells (ESCs) and a mouse model both harboring the p.H222P Lmna mutation, we found early defects in cardiac differentiation of mutated ESCs and dilatation of mutated embryonic hearts at E13.5, pointing to a developmental origin of the disease. Using mouse ESCs, we demonstrated that cardiac differentiation of Lmna(H222P/+) was impaired at the mesodermal stage. Expression of Mesp1, a mesodermal cardiogenic gene involved in epithelial-to-mesenchymal transition of epiblast cells, as well as Snail and Twist expression, was decreased in Lmna(H222P/+) cells compared with WT cells in the course of differentiation. In turn, cardiomyocyte differentiation was impaired. ChIP assay of H3K4me1 in differentiating cells revealed a specific decrease of this histone mark on regulatory regions of Mespl and Twist in Lmna(H222P/+) cells. Downregulation or inhibition of LSD1 that specifically demethylated H3K4me1 rescued the epigenetic landscape of mesodermal Lmna(H222P/+) cells and in turn contraction of cardiomyocytes. Inhibition of LSD1 in pregnant mice or neonatal mice prevented cardiomyopathy in E13.5 Lmna(H222P/H222P) offspring and adults, respectively. Thus, LSD1 appeared to be a therapeutic target to prevent or cure dilated cardiomyopathy associated with a Laminopathy.
-
A common French-Italian Laminopathy registry – update & future prospects
Orphanet Journal of Rare Diseases, 2015Co-Authors: Gisèle Bonne, Rabah Ben YaouAbstract:International audienceIn front of the wide clinical and genetic heterogeneity of the laminopathies, the first task of the French Network on EDMD and other related nuclear envelope related diseases, has been to set up in 2000, a mutation database for LMNA and EMD mutations. We selected the Universal Mutation Database tool (UMD) developed by Christophe Beroud (http://www.umd.be,[1]) and set up the UMD-LMNA database that compiles genetic and associated main clinical features of both in-house identified cases, those submitted to us by other partners involved in LMNA gene analysis, and also all mutated subjects reported in the literature (http://www.umd.be/LMNA/). To date, the UMD-LMNA database comprises 510 different LMNA mutations identified in over 2700 individuals, out of which 60% presenting with a Laminopathy of the striated muscles (cardiomyopathies+/-muscular dystrophies), 14% with a Laminopathy affecting the adipose tissue (metabolic syndromes +/- partial lipodystrophies) and 5.2% with premature ageing syndrome
-
A common French-Italian Laminopathy registry – update & future prospects
Orphanet Journal of Rare Diseases, 2015Co-Authors: Gisèle Bonne, Rabah Ben YaouAbstract:In front of the wide clinical and genetic heterogeneity of the laminopathies, the first task of the French Network on EDMD and other related nuclear envelope related diseases, has been to set up in 2000, a mutation database for LMNA and EMD mutations. We selected the Universal Mutation Database tool (UMD) developed by Christophe Beroud (http://www.umd.be,[1]) and set up the UMD-LMNA database that compiles genetic and associated main clinical features of both in-house identified cases, those submitted to us by other partners involved in LMNA gene analysis, and also all mutated subjects reported in the literature (http://www.umd.be/LMNA/). To date, the UMD-LMNA database comprises 510 different LMNA mutations identified in over 2700 individuals, out of which 60% presenting with a Laminopathy of the striated muscles (cardiomyopathies+/-muscular dystrophies), 14% with a Laminopathy affecting the adipose tissue (metabolic syndromes +/- partial lipodystrophies) and 5.2% with premature ageing syndrome. For rare diseases, a major hurdle in clinical translation of basic science research results is the difficulty in identifying appropriate patient cohorts. Prospective data on patient clinical characteristics, specific biomarkers and outcome measures are also frequently unavailable. With the aim to obtain longitudinal clinical data on patients with Laminopathy or emerinopathy (as well as asymptomatic carriers at the time of genetic diagnosis) and create corresponding “trial-readiness” patient registries, we set-up in 2013 a prospective patient registry, the OPALE registry (for “Observatoire des Patients Atteints de Laminopathie et Emerinopathie”). This registry will allow precise characterization of the disease natural history, identification of specific outcome measures and further evaluation of the prognostic value of various biomarkers. The overall goals of OPALE are 1) a better follow-up and management of the patients and 2) the identification of specific parameters to monitor treatments in the perspective of future clinical trials. OPALE has been initiated within 3 pilot centers (neuromuscular reference center at the Myology Institute, cardiology department of Cochin university hospital in Paris, neuropediatric department of Raymond Poincare university hospital in Garches) and thanks to the strong links within the French Networks of “EDMD & other nuclear envelope related diseases”, OPALE is now progressively opened to other French reference centers, once the approvals of IRB/ethics committee and other regulatory authority have been obtained. To date, 78 patients have been included in this registry among 170 followed within the 3 pilot centers. Regular update of the collected data are planned. We plan to open the registry to international colleagues via our interaction with the Italian network for Laminopathies, with the TREAT-NMD networks as well as any other center interested in this initiative. We hope the OPALE registry will become rapidly an international interactive tool for the benefit of Laminopathy and emerinopathy patients.
-
a common french italian Laminopathy registry update future prospects
Orphanet Journal of Rare Diseases, 2015Co-Authors: Gisèle Bonne, Rabah Ben YaouAbstract:In front of the wide clinical and genetic heterogeneity of the laminopathies, the first task of the French Network on EDMD and other related nuclear envelope related diseases, has been to set up in 2000, a mutation database for LMNA and EMD mutations. We selected the Universal Mutation Database tool (UMD) developed by Christophe Beroud (http://www.umd.be,[1]) and set up the UMD-LMNA database that compiles genetic and associated main clinical features of both in-house identified cases, those submitted to us by other partners involved in LMNA gene analysis, and also all mutated subjects reported in the literature (http://www.umd.be/LMNA/). To date, the UMD-LMNA database comprises 510 different LMNA mutations identified in over 2700 individuals, out of which 60% presenting with a Laminopathy of the striated muscles (cardiomyopathies+/-muscular dystrophies), 14% with a Laminopathy affecting the adipose tissue (metabolic syndromes +/- partial lipodystrophies) and 5.2% with premature ageing syndrome. For rare diseases, a major hurdle in clinical translation of basic science research results is the difficulty in identifying appropriate patient cohorts. Prospective data on patient clinical characteristics, specific biomarkers and outcome measures are also frequently unavailable. With the aim to obtain longitudinal clinical data on patients with Laminopathy or emerinopathy (as well as asymptomatic carriers at the time of genetic diagnosis) and create corresponding “trial-readiness” patient registries, we set-up in 2013 a prospective patient registry, the OPALE registry (for “Observatoire des Patients Atteints de Laminopathie et Emerinopathie”). This registry will allow precise characterization of the disease natural history, identification of specific outcome measures and further evaluation of the prognostic value of various biomarkers. The overall goals of OPALE are 1) a better follow-up and management of the patients and 2) the identification of specific parameters to monitor treatments in the perspective of future clinical trials. OPALE has been initiated within 3 pilot centers (neuromuscular reference center at the Myology Institute, cardiology department of Cochin university hospital in Paris, neuropediatric department of Raymond Poincare university hospital in Garches) and thanks to the strong links within the French Networks of “EDMD & other nuclear envelope related diseases”, OPALE is now progressively opened to other French reference centers, once the approvals of IRB/ethics committee and other regulatory authority have been obtained. To date, 78 patients have been included in this registry among 170 followed within the 3 pilot centers. Regular update of the collected data are planned. We plan to open the registry to international colleagues via our interaction with the Italian network for Laminopathies, with the TREAT-NMD networks as well as any other center interested in this initiative. We hope the OPALE registry will become rapidly an international interactive tool for the benefit of Laminopathy and emerinopathy patients.
-
A common French-Italian Laminopathy registry – update & future prospects
Orphanet Journal of Rare Diseases, 2015Co-Authors: Gisèle Bonne, Rabah Ben YaouAbstract:In front of the wide clinical and genetic heterogeneity of the laminopathies, the first task of the French Network on EDMD and other related nuclear envelope related diseases, has been to set up in 2000, a mutation database for LMNA and EMD mutations. We selected the Universal Mutation Database tool (UMD) developed by Christophe Beroud (http://www.umd.be,[1]) and set up the UMD-LMNA database that compiles genetic and associated main clinical features of both in-house identified cases, those submitted to us by other partners involved in LMNA gene analysis, and also all mutated subjects reported in the literature (http://www.umd.be/LMNA/). To date, the UMD-LMNA database comprises 510 different LMNA mutations identified in over 2700 individuals, out of which 60% presenting with a Laminopathy of the striated muscles (cardiomyopathies+/-muscular dystrophies), 14% with a Laminopathy affecting the adipose tissue (metabolic syndromes +/- partial lipodystrophies) and 5.2% with premature ageing syndrome.
Rabah Ben Yaou - One of the best experts on this subject based on the ideXlab platform.
-
A common French-Italian Laminopathy registry – update & future prospects
Orphanet Journal of Rare Diseases, 2015Co-Authors: Gisèle Bonne, Rabah Ben YaouAbstract:In front of the wide clinical and genetic heterogeneity of the laminopathies, the first task of the French Network on EDMD and other related nuclear envelope related diseases, has been to set up in 2000, a mutation database for LMNA and EMD mutations. We selected the Universal Mutation Database tool (UMD) developed by Christophe Beroud (http://www.umd.be,[1]) and set up the UMD-LMNA database that compiles genetic and associated main clinical features of both in-house identified cases, those submitted to us by other partners involved in LMNA gene analysis, and also all mutated subjects reported in the literature (http://www.umd.be/LMNA/). To date, the UMD-LMNA database comprises 510 different LMNA mutations identified in over 2700 individuals, out of which 60% presenting with a Laminopathy of the striated muscles (cardiomyopathies+/-muscular dystrophies), 14% with a Laminopathy affecting the adipose tissue (metabolic syndromes +/- partial lipodystrophies) and 5.2% with premature ageing syndrome. For rare diseases, a major hurdle in clinical translation of basic science research results is the difficulty in identifying appropriate patient cohorts. Prospective data on patient clinical characteristics, specific biomarkers and outcome measures are also frequently unavailable. With the aim to obtain longitudinal clinical data on patients with Laminopathy or emerinopathy (as well as asymptomatic carriers at the time of genetic diagnosis) and create corresponding “trial-readiness” patient registries, we set-up in 2013 a prospective patient registry, the OPALE registry (for “Observatoire des Patients Atteints de Laminopathie et Emerinopathie”). This registry will allow precise characterization of the disease natural history, identification of specific outcome measures and further evaluation of the prognostic value of various biomarkers. The overall goals of OPALE are 1) a better follow-up and management of the patients and 2) the identification of specific parameters to monitor treatments in the perspective of future clinical trials. OPALE has been initiated within 3 pilot centers (neuromuscular reference center at the Myology Institute, cardiology department of Cochin university hospital in Paris, neuropediatric department of Raymond Poincare university hospital in Garches) and thanks to the strong links within the French Networks of “EDMD & other nuclear envelope related diseases”, OPALE is now progressively opened to other French reference centers, once the approvals of IRB/ethics committee and other regulatory authority have been obtained. To date, 78 patients have been included in this registry among 170 followed within the 3 pilot centers. Regular update of the collected data are planned. We plan to open the registry to international colleagues via our interaction with the Italian network for Laminopathies, with the TREAT-NMD networks as well as any other center interested in this initiative. We hope the OPALE registry will become rapidly an international interactive tool for the benefit of Laminopathy and emerinopathy patients.
-
a common french italian Laminopathy registry update future prospects
Orphanet Journal of Rare Diseases, 2015Co-Authors: Gisèle Bonne, Rabah Ben YaouAbstract:In front of the wide clinical and genetic heterogeneity of the laminopathies, the first task of the French Network on EDMD and other related nuclear envelope related diseases, has been to set up in 2000, a mutation database for LMNA and EMD mutations. We selected the Universal Mutation Database tool (UMD) developed by Christophe Beroud (http://www.umd.be,[1]) and set up the UMD-LMNA database that compiles genetic and associated main clinical features of both in-house identified cases, those submitted to us by other partners involved in LMNA gene analysis, and also all mutated subjects reported in the literature (http://www.umd.be/LMNA/). To date, the UMD-LMNA database comprises 510 different LMNA mutations identified in over 2700 individuals, out of which 60% presenting with a Laminopathy of the striated muscles (cardiomyopathies+/-muscular dystrophies), 14% with a Laminopathy affecting the adipose tissue (metabolic syndromes +/- partial lipodystrophies) and 5.2% with premature ageing syndrome. For rare diseases, a major hurdle in clinical translation of basic science research results is the difficulty in identifying appropriate patient cohorts. Prospective data on patient clinical characteristics, specific biomarkers and outcome measures are also frequently unavailable. With the aim to obtain longitudinal clinical data on patients with Laminopathy or emerinopathy (as well as asymptomatic carriers at the time of genetic diagnosis) and create corresponding “trial-readiness” patient registries, we set-up in 2013 a prospective patient registry, the OPALE registry (for “Observatoire des Patients Atteints de Laminopathie et Emerinopathie”). This registry will allow precise characterization of the disease natural history, identification of specific outcome measures and further evaluation of the prognostic value of various biomarkers. The overall goals of OPALE are 1) a better follow-up and management of the patients and 2) the identification of specific parameters to monitor treatments in the perspective of future clinical trials. OPALE has been initiated within 3 pilot centers (neuromuscular reference center at the Myology Institute, cardiology department of Cochin university hospital in Paris, neuropediatric department of Raymond Poincare university hospital in Garches) and thanks to the strong links within the French Networks of “EDMD & other nuclear envelope related diseases”, OPALE is now progressively opened to other French reference centers, once the approvals of IRB/ethics committee and other regulatory authority have been obtained. To date, 78 patients have been included in this registry among 170 followed within the 3 pilot centers. Regular update of the collected data are planned. We plan to open the registry to international colleagues via our interaction with the Italian network for Laminopathies, with the TREAT-NMD networks as well as any other center interested in this initiative. We hope the OPALE registry will become rapidly an international interactive tool for the benefit of Laminopathy and emerinopathy patients.
Rabah Ben Yaou - One of the best experts on this subject based on the ideXlab platform.
-
A common French-Italian Laminopathy registry – update & future prospects
Orphanet Journal of Rare Diseases, 2015Co-Authors: Gisèle Bonne, Rabah Ben YaouAbstract:International audienceIn front of the wide clinical and genetic heterogeneity of the laminopathies, the first task of the French Network on EDMD and other related nuclear envelope related diseases, has been to set up in 2000, a mutation database for LMNA and EMD mutations. We selected the Universal Mutation Database tool (UMD) developed by Christophe Beroud (http://www.umd.be,[1]) and set up the UMD-LMNA database that compiles genetic and associated main clinical features of both in-house identified cases, those submitted to us by other partners involved in LMNA gene analysis, and also all mutated subjects reported in the literature (http://www.umd.be/LMNA/). To date, the UMD-LMNA database comprises 510 different LMNA mutations identified in over 2700 individuals, out of which 60% presenting with a Laminopathy of the striated muscles (cardiomyopathies+/-muscular dystrophies), 14% with a Laminopathy affecting the adipose tissue (metabolic syndromes +/- partial lipodystrophies) and 5.2% with premature ageing syndrome
-
A common French-Italian Laminopathy registry – update & future prospects
Orphanet Journal of Rare Diseases, 2015Co-Authors: Gisèle Bonne, Rabah Ben YaouAbstract:In front of the wide clinical and genetic heterogeneity of the laminopathies, the first task of the French Network on EDMD and other related nuclear envelope related diseases, has been to set up in 2000, a mutation database for LMNA and EMD mutations. We selected the Universal Mutation Database tool (UMD) developed by Christophe Beroud (http://www.umd.be,[1]) and set up the UMD-LMNA database that compiles genetic and associated main clinical features of both in-house identified cases, those submitted to us by other partners involved in LMNA gene analysis, and also all mutated subjects reported in the literature (http://www.umd.be/LMNA/). To date, the UMD-LMNA database comprises 510 different LMNA mutations identified in over 2700 individuals, out of which 60% presenting with a Laminopathy of the striated muscles (cardiomyopathies+/-muscular dystrophies), 14% with a Laminopathy affecting the adipose tissue (metabolic syndromes +/- partial lipodystrophies) and 5.2% with premature ageing syndrome.
Winghon Lai - One of the best experts on this subject based on the ideXlab platform.
-
recent advances in animal and human pluripotent stem cell modeling of cardiac Laminopathy
Stem Cell Research & Therapy, 2016Co-Authors: Yeeki Lee, Yu Jiang, Xinru Ran, Yeeman Lau, Winghon LaiAbstract:Laminopathy is a disease closely related to deficiency of the nuclear matrix protein lamin A/C or failure in prelamin A processing, and leads to accumulation of the misfold protein causing progeria. The resultant disrupted lamin function is highly associated with abnormal nuclear architecture, cell senescence, apoptosis, and unstable genome integrity. To date, the effects of loss in nuclear integrity on the susceptible organ, striated muscle, have been commonly associated with muscular dystrophy, dilated cardiac myopathy (DCM), and conduction defeats, but have not been studied intensively. In this review, we aim to summarize recent breakthroughs in an in vivo Laminopathy model and in vitro study using patient-specific human induced pluripotent stem cells (iPSCs) that reproduce the pathophysiological phenotype for further drug screening. We describe several in-vivo transgenic mouse models to elucidate the effects of Lmna H222P, N195K mutations, and LMNA knockout on cardiac function, in terms of hemodynamic and electrical signal propagation; certain strategies targeted on stress-related MAPK are mentioned. We will also discuss human iPSC cardiomyocytes serving as a platform to reveal the underlying mechanisms, such as the altered mechanical sensation in electrical coupling of the heart conduction system and ion channel alternation in relation to altered nuclear architecture, and furthermore to enable screening of drugs that can attenuate this cardiac premature aging phenotype by inhibition of prelamin misfolding and oxidative stress, and also enhancement of autophagy protein clearance and cardiac-protective microRNA.
Yeeki Lee - One of the best experts on this subject based on the ideXlab platform.
-
recent advances in animal and human pluripotent stem cell modeling of cardiac Laminopathy
Stem Cell Research & Therapy, 2016Co-Authors: Yeeki Lee, Yu Jiang, Xinru Ran, Yeeman Lau, Winghon LaiAbstract:Laminopathy is a disease closely related to deficiency of the nuclear matrix protein lamin A/C or failure in prelamin A processing, and leads to accumulation of the misfold protein causing progeria. The resultant disrupted lamin function is highly associated with abnormal nuclear architecture, cell senescence, apoptosis, and unstable genome integrity. To date, the effects of loss in nuclear integrity on the susceptible organ, striated muscle, have been commonly associated with muscular dystrophy, dilated cardiac myopathy (DCM), and conduction defeats, but have not been studied intensively. In this review, we aim to summarize recent breakthroughs in an in vivo Laminopathy model and in vitro study using patient-specific human induced pluripotent stem cells (iPSCs) that reproduce the pathophysiological phenotype for further drug screening. We describe several in-vivo transgenic mouse models to elucidate the effects of Lmna H222P, N195K mutations, and LMNA knockout on cardiac function, in terms of hemodynamic and electrical signal propagation; certain strategies targeted on stress-related MAPK are mentioned. We will also discuss human iPSC cardiomyocytes serving as a platform to reveal the underlying mechanisms, such as the altered mechanical sensation in electrical coupling of the heart conduction system and ion channel alternation in relation to altered nuclear architecture, and furthermore to enable screening of drugs that can attenuate this cardiac premature aging phenotype by inhibition of prelamin misfolding and oxidative stress, and also enhancement of autophagy protein clearance and cardiac-protective microRNA.
