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Article ; Online: Paediatric multisystem inflammatory syndrome associated with COVID-19: filling the gap between myocarditis and Kawasaki?

Bordet, Jeanne / Perrier, Stéphanie / Olexa, Catherine / Gerout, Anne-Cécile / Billaud, Philippe / Bonnemains, Laurent

2020 Volume 180, Issue 3, Page(s) 877–884

Abstract: Myocarditis and Kawasaki disease are common but usually distinct diseases in children. During the coronavirus pandemic (COVID-19), reports of a new form of myocarditis with clinical features of Kawasaki appeared. We investigated the place of this new ... ...

Abstract	Myocarditis and Kawasaki disease are common but usually distinct diseases in children. During the coronavirus pandemic (COVID-19), reports of a new form of myocarditis with clinical features of Kawasaki appeared. We investigated the place of this new disease in the spectrum encompassing Kawasaki disease and myocarditis.Thirty two consecutive children referred to our centre for a suspicion of Kawasaki or a diagnosis of myocarditis were included and eventually divided into four groups: 11 Kawasaki diseases, 6 Kawasaki syndromes (children with another diagnosis), 7 myocarditis without Kawasaki clinical feature and 7 myocarditis with incomplete Kawasaki clinical features. All were treated with immunoglobulins except those of the myocarditis group. The survival rate was 91%. The 7 children with myocarditis and clinical features of incomplete Kawasaki were all positive for SARS-CoV-2. They had a transient myocardial failure with a favourable course and none had coronary artery disease.Conclusion: Every COVID-19 child within our population had a mild to severe myocarditis and presented with fever plus two or three Kawasaki clinical features. Short-term evolution was good for these children. This new disease seems to fill the gap between isolated myocarditis and Kawasaki disease. What is Known: • A new paediatric disease close to Kawasaki disease appeared during the COVID-19 pandemic What is New: • In our population, children presented with fever, vivid Kawasaki clinical features (although the Kawasaki syndrome was always incomplete) and a myocarditis without coronary abnormalities. • The new disease fills the gap between paediatric myocarditis and Kawasaki disease but its prognosis is much better.
MeSH term(s)	Adolescent ; COVID-19/complications ; COVID-19/diagnosis ; Child ; Child, Preschool ; Diagnosis, Differential ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mucocutaneous Lymph Node Syndrome/diagnosis ; Mucocutaneous Lymph Node Syndrome/virology ; Myocarditis/diagnosis ; Myocarditis/virology ; Retrospective Studies ; Systemic Inflammatory Response Syndrome/complications ; Systemic Inflammatory Response Syndrome/diagnosis
Keywords	covid19
Language	English
Publishing date	2020-09-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	194196-3
ISSN	1432-1076 ; 0340-6199 ; 0943-9676
ISSN (online)	1432-1076
ISSN	0340-6199 ; 0943-9676
DOI	10.1007/s00431-020-03807-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Paediatric multisystem inflammatory syndrome associated with COVID-19

Bordet, Jeanne / Perrier, Stéphanie / Olexa, Catherine / Gerout, Anne-Cécile / Billaud, Philippe / Bonnemains, Laurent

European Journal of Pediatrics ; ISSN 0340-6199 1432-1076

filling the gap between myocarditis and Kawasaki?

2020

Keywords	Pediatrics, Perinatology, and Child Health ; covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
DOI	10.1007/s00431-020-03807-0
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Paediatric multisystem inflammatory syndrome associated with COVID-19: filling the gap between myocarditis and Kawasaki?

Bordet, Jeanne / Perrier, Stéphanie / Olexa, Catherine / Gerout, Anne-Cécile / Billaud, Philippe / Bonnemains, Laurent

Eur. j. pediatr

Abstract	Myocarditis and Kawasaki disease are common but usually distinct diseases in children. During the coronavirus pandemic (COVID-19), reports of a new form of myocarditis with clinical features of Kawasaki appeared. We investigated the place of this new disease in the spectrum encompassing Kawasaki disease and myocarditis.Thirty two consecutive children referred to our centre for a suspicion of Kawasaki or a diagnosis of myocarditis were included and eventually divided into four groups: 11 Kawasaki diseases, 6 Kawasaki syndromes (children with another diagnosis), 7 myocarditis without Kawasaki clinical feature and 7 myocarditis with incomplete Kawasaki clinical features. All were treated with immunoglobulins except those of the myocarditis group. The survival rate was 91%. The 7 children with myocarditis and clinical features of incomplete Kawasaki were all positive for SARS-CoV-2. They had a transient myocardial failure with a favourable course and none had coronary artery disease.Conclusion: Every COVID-19 child within our population had a mild to severe myocarditis and presented with fever plus two or three Kawasaki clinical features. Short-term evolution was good for these children. This new disease seems to fill the gap between isolated myocarditis and Kawasaki disease. What is Known: â¢ A new paediatric disease close to Kawasaki disease appeared during the COVID-19 pandemic What is New: â¢ In our population, children presented with fever, vivid Kawasaki clinical features (although the Kawasaki syndrome was always incomplete) and a myocarditis without coronary abnormalities. â¢ The new disease fills the gap between paediatric myocarditis and Kawasaki disease but its prognosis is much better.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #777827
Database	COVID19

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Article ; Online: Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children.

Ouldali, Naïm / Toubiana, Julie / Antona, Denise / Javouhey, Etienne / Madhi, Fouad / Lorrot, Mathie / Léger, Pierre-Louis / Galeotti, Caroline / Claude, Caroline / Wiedemann, Arnaud / Lachaume, Noémie / Ovaert, Caroline / Dumortier, Morgane / Kahn, Jean-Emmanuel / Mandelcwajg, Alexis / Percheron, Lucas / Biot, Blandine / Bordet, Jeanne / Girardin, Marie-Laure /

Yang, David Dawei / Grimaud, Marion / Oualha, Mehdi / Allali, Slimane / Bajolle, Fanny / Beyler, Constance / Meinzer, Ulrich / Levy, Michael / Paulet, Ana-Maria / Levy, Corinne / Cohen, Robert / Belot, Alexandre / Angoulvant, François

JAMA

2021 Volume 325, Issue 9, Page(s) 855–864

Abstract: Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains ... ...

Abstract	Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, setting, and participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main outcomes and measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.
MeSH term(s)	Adolescent ; COVID-19/complications ; COVID-19/drug therapy ; COVID-19/therapy ; Child ; Child, Preschool ; Combined Modality Therapy ; Female ; Fever/etiology ; France ; Glucocorticoids/adverse effects ; Glucocorticoids/therapeutic use ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Intensive Care Units, Pediatric ; Length of Stay ; Male ; Methylprednisolone/adverse effects ; Methylprednisolone/therapeutic use ; Propensity Score ; Recurrence ; Retrospective Studies ; Systemic Inflammatory Response Syndrome/complications ; Systemic Inflammatory Response Syndrome/drug therapy ; Systemic Inflammatory Response Syndrome/therapy ; Treatment Outcome
Chemical Substances	Glucocorticoids ; Immunoglobulins, Intravenous ; Methylprednisolone (X4W7ZR7023)
Language	English
Publishing date	2021-02-01
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2958-0
ISSN	1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
ISSN (online)	1538-3598
ISSN	0254-9077 ; 0002-9955 ; 0098-7484
DOI	10.1001/jama.2021.0694
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Article ; Online: Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic.

Belhadjer, Zahra / Méot, Mathilde / Bajolle, Fanny / Khraiche, Diala / Legendre, Antoine / Abakka, Samya / Auriau, Johanne / Grimaud, Marion / Oualha, Mehdi / Beghetti, Maurice / Wacker, Julie / Ovaert, Caroline / Hascoet, Sebastien / Selegny, Maëlle / Malekzadeh-Milani, Sophie / Maltret, Alice / Bosser, Gilles / Giroux, Nathan / Bonnemains, Laurent /

Bordet, Jeanne / Di Filippo, Sylvie / Mauran, Pierre / Falcon-Eicher, Sylvie / Thambo, Jean-Benoît / Lefort, Bruno / Moceri, Pamela / Houyel, Lucile / Renolleau, Sylvain / Bonnet, Damien

Circulation

2020 Volume 142, Issue 5, Page(s) 429–436

Abstract: Background: Cardiac injury and myocarditis have been described in adults with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is typically minimally symptomatic. We report a series ... ...

Abstract	Background: Cardiac injury and myocarditis have been described in adults with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children as defined by the US Centers for Disease Control and Prevention. Methods: Over a 2-month period, contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Results: Thirty-five children were identified and included in the study. Median age at admission was 10 years (range, 2-16 years). Comorbidities were present in 28%, including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was <30% in one-third; 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation. Inflammation markers were suggestive of cytokine storm (interleukin-6 median, 135 pg/mL) and macrophage activation (D-dimer median, 5284 ng/mL). Mean BNP (B-type natriuretic peptide) was elevated (5743 pg/mL). Thirty-one of 35 patients (88%) tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. All patients received intravenous immunoglobulin, with adjunctive steroid therapy used in one-third. Left ventricular function was restored in the 25 of 35 of those discharged from the intensive care unit. No patient died, and all patients treated with extracorporeal membrane oxygenation were successfully weaned. Conclusions: Children may experience an acute cardiac decompensation caused by severe inflammatory state after SARS-CoV-2 infection (multisystem inflammatory syndrome in children). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.
MeSH term(s)	Adolescent ; COVID-19/complications ; COVID-19/virology ; Child ; Female ; Heart Failure/complications ; Heart Failure/drug therapy ; Heart Failure/virology ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Inflammation/complications ; Inflammation/drug therapy ; Inflammation/virology ; Male ; Retrospective Studies ; Stroke Volume/physiology ; Systemic Inflammatory Response Syndrome/complications ; Systemic Inflammatory Response Syndrome/virology ; Ventricular Dysfunction, Left/drug therapy ; Ventricular Function, Left/immunology
Chemical Substances	Immunoglobulins, Intravenous
Keywords	covid19
Language	English
Publishing date	2020-05-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.120.048360
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Article: Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic

Bordet, Jeanne / Di Filippo, Sylvie / Mauran, Pierre / Falcon-Eicher, Sylvie / Thambo, Jean-Benoît / Lefort, Bruno / Moceri, Pamela / Houyel, Lucile / Renolleau, Sylvain / Bonnet, Damien

Circulation

Abstract: Background: Cardiac injury and myocarditis have been described in adults with COVID-19. SARS-CoV-2 infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated ... ...

Abstract	Background: Cardiac injury and myocarditis have been described in adults with COVID-19. SARS-CoV-2 infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children (MIS-C) as defined by the US Centers for Disease Control. Methods: Over a two-month period contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction and severe inflammatory state. Results: Thirty-five children were identified and included in the study. Median age at admission was 10 years (range 2-16 years). Co-morbidities were present in 28% including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was <30% in one third; 80% required inotropic support with 28% treated with ECMO. Inflammation markers were suggestive of cytokine storm (interleukin 6 median 135 pg/mL) and macrophage activation (D-dimer median 5284 ng/mL). Mean brain natriuretic peptide was elevated (5743 pg/mL). Thirty-one/35 (88%) patients tested positive for SARS-CoV-2 infection by PCR of nasopharyngeal swab or serology. All patients received intravenous immune globulin, with adjunctive steroid therapy used in one third. Left ventricular function was restored in the 25/35 of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned. Conclusion: Children may experience an acute cardiac decompensation due to severe inflammatory state following SARS-CoV-2 infection (multisystem inflammatory syndrome in children - MIS-C). Treatment with immune globulin appears to be associated with recovery of left ventricular systolic function.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #32418446
Database	COVID19

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Article ; Online: Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic

Bordet, Jeanne / Di Filippo, Sylvie / Mauran, Pierre / Falcon-Eicher, Sylvie / Thambo, Jean-Benoît / Lefort, Bruno / Moceri, Pamela / Houyel, Lucile / Renolleau, Sylvain / Bonnet, Damien

Circulation

2020 Volume 142, Issue 5, Page(s) 429–436

Abstract	Background: Cardiac injury and myocarditis have been described in adults with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children as defined by the US Centers for Disease Control and Prevention. Methods: Over a 2-month period, contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Results: Thirty-five children were identified and included in the study. Median age at admission was 10 years (range, 2–16 years). Comorbidities were present in 28%, including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was <30% in one-third; 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation. Inflammation markers were suggestive of cytokine storm (interleukin-6 median, 135 pg/mL) and macrophage activation (D-dimer median, 5284 ng/mL). Mean BNP (B-type natriuretic peptide) was elevated (5743 pg/mL). Thirty-one of 35 patients (88%) tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. All patients received intravenous immunoglobulin, with adjunctive steroid therapy used in one-third. Left ventricular function was restored in the 25 of 35 of those discharged from the intensive care unit. No patient died, and all patients treated with extracorporeal membrane oxygenation were successfully weaned. Conclusions: Children may experience an acute cardiac decompensation caused by severe inflammatory state after SARS-CoV-2 infection (multisystem inflammatory syndrome in children). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.
Keywords	Physiology (medical) ; Cardiology and Cardiovascular Medicine ; covid19
Language	English
Publisher	Ovid Technologies (Wolters Kluwer Health)
Publishing country	us
Document type	Article ; Online
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/circulationaha.120.048360
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Therapeutic benefits of cardiotrophin-1 gene transfer in a mouse model of spinal muscular atrophy.

Lesbordes, Jeanne-Claire / Cifuentes-Diaz, Carmen / Miroglio, Audrey / Joshi, Vandana / Bordet, Thierry / Kahn, Axel / Melki, Judith

Human molecular genetics

2003 Volume 12, Issue 11, Page(s) 1233–1239

Abstract: Spinal muscular atrophy (SMA) is a recessive autosomal disorder characterized by degeneration of lower motor neurons caused by mutations of the survival motor neuron gene (SMN1). No curative treatment is known so far. Mutant mice carrying homozygous ... ...

Abstract	Spinal muscular atrophy (SMA) is a recessive autosomal disorder characterized by degeneration of lower motor neurons caused by mutations of the survival motor neuron gene (SMN1). No curative treatment is known so far. Mutant mice carrying homozygous deletion of Smn exon 7 directed to neurons display skeletal muscle denervation, moderate loss of motor neuron cell bodies and severe axonal degeneration. These features, similar to those found in human SMA, strongly suggest the involvement of a dying back process of motor neurons and led us to test whether neurotrophic factors might have a protective role in SMA. We report here the therapeutic benefits of systemic delivery of cardiotrophin-1 (CT-1), a neurotrophic factor belonging to the IL-6 cytokine family. Intra-muscular injection of adenoviral vector expressing CT-1, even at very low dose, improves median survival, delays motor defect of mutant mice and exerts protective effect against loss of proximal motor axons and aberrant cytoskeletal organization of motor synaptic terminals. In spite of the severity of SMA phenotype in mutant mice, CT-1 is able to slow down disease progression. Neuroprotection could be regarded as valuable therapeutic approach in SMA.
MeSH term(s)	Animals ; Axons/drug effects ; Axons/pathology ; Cytokines/genetics ; Cytokines/therapeutic use ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Gene Transfer Techniques ; Genetic Therapy/methods ; Genetic Vectors/administration & dosage ; Genetic Vectors/adverse effects ; Genetic Vectors/genetics ; Humans ; Injections, Intramuscular ; Mice ; Mice, Mutant Strains ; Muscular Atrophy, Spinal/genetics ; Muscular Atrophy, Spinal/physiopathology ; Muscular Atrophy, Spinal/therapy ; Neuromuscular Junction/drug effects ; Neuromuscular Junction/pathology ; Phrenic Nerve/drug effects ; Phrenic Nerve/pathology ; Survival Rate
Chemical Substances	Cytokines ; cardiotrophin 1 (AJ7U77BR8I)
Language	English
Publishing date	2003-05-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddg143
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Article: In vivo electrotransfer of the cardiotrophin-1 gene into skeletal muscle slows down progression of motor neuron degeneration in pmn mice.

Lesbordes, Jeanne-Claire / Bordet, Thierry / Haase, Georg / Castelnau-Ptakhine, Laetitia / Rouhani, Saïd / Gilgenkrantz, Helène / Kahn, Axel

Human molecular genetics

2002 Volume 11, Issue 14, Page(s) 1615–1625

Abstract: Among all vectors designed for gene therapy purposes, adenovirus appears to be the most efficient in vivo vehicle to transduce the broadest spectrum of cellular targets. However, the deleterious immunogenicity of this viral vector impedes its use in ... ...

Abstract	Among all vectors designed for gene therapy purposes, adenovirus appears to be the most efficient in vivo vehicle to transduce the broadest spectrum of cellular targets. However, the deleterious immunogenicity of this viral vector impedes its use in chronic diseases. Non-viral vectors, such as naked DNA, are attractive alternatives for safety and technical issues, such as scale-up production. Naked DNA injection, greatly improved when combined with electroporation, showed great potential in adult animals, especially when directed to the muscle. We have recently proven the therapeutic effect of a neonatal single intramuscular injection of a cardiotrophin-1 (CT-1)-encoding adenovirus in a hereditary disease mouse model of human motor neuron disease, the progressive motor neuronopathy (pmn) mutant. We now demonstrate that a single injection/electroporation of a CT-1-encoding plasmid in neonate pmn mice is almost as efficient as adenovirus-mediated gene transfer with respect to survival, muscular function and neuroprotection of the animals. Treated mice gain global weight, their mean lifespan is extended by 25%, all their electromyographic parameters are improved and myelinated axons of their phrenic nerves are protected. Moreover, we show that re-injection/electroporation leads to improvements in this neuroprotection. We therefore demonstrate for the first time the therapeutic efficacy of neonatal intramuscular DNA injection/electroporation in a murine model of a human hereditary disorder.
MeSH term(s)	Animals ; Animals, Newborn ; Body Weight/genetics ; Cytokines/genetics ; Cytokines/metabolism ; Dose-Response Relationship, Drug ; Electroporation/methods ; Gene Transfer Techniques ; Genetic Therapy/methods ; Mice ; Mice, Neurologic Mutants ; Motor Neuron Disease/genetics ; Motor Neuron Disease/therapy ; Motor Neurons/drug effects ; Motor Neurons/pathology ; Motor Neurons/physiology ; Muscle, Skeletal/physiology ; Nerve Degeneration/genetics ; Nerve Degeneration/pathology ; Nerve Degeneration/therapy ; Plasmids/genetics ; Plasmids/pharmacology ; Survival Rate ; beta-Galactosidase/genetics
Chemical Substances	Cytokines ; cardiotrophin 1 (AJ7U77BR8I) ; beta-Galactosidase (EC 3.2.1.23)
Language	English
Publishing date	2002-07-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/11.14.1615
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