Valérie Decostre

Valérie Decostre
Institute of Myology

Biomedical Sciences Ph D

About

83
Publications
9,914
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Introduction
Additional affiliations
January 2009 - present
Institut de Myologie
Description
  • Outcome measures in preclinical and clinical research on myopathies
November 2004 - December 2008
French Institute of Health and Medical Research
Description
  • Emery-Dreifuss muscular dystrophy
May 2002 - September 2004
University of Florence
Description
  • Effect of temperature on the working stroke of muscle myosin.

Publications

Publications (83)
Article
Full-text available
Objective To understand the natural disease upper limb progression over 3 years of ambulatory and non-ambulatory patients with Duchenne muscular dystrophy (DMD) using functional assessments and quantitative magnetic resonance imaging (MRI) and to exploratively identify prognostic factors. Methods Forty boys with DMD (22 non-ambulatory and 18 ambul...
Article
Full-text available
Cofilins are important for the regulation of the actin cytoskeleton, sarcomere organization, and force production. The role of cofilin-1, the non-muscle-specific isoform, in muscle function remains unclear. Mutations in LMNA encoding A-type lamins, intermediate filament proteins of the nuclear envelope, cause autosomal Emery-Dreifuss muscular dystr...
Article
Full-text available
Objective The main aim was to explore the changes in hand-grip strength in patients with Duchenne muscular dystrophy (DMD) aged 5–29 years. Secondary aims were to test the effect of mutation, ambulatory status and glucocorticoid use on grip strength and its changes over time and to compute the number of subjects needed for a clinical trial to stabi...
Article
Introduction The main objective of this study was to describe muscle involvement on whole‐body MRI (WB‐MRI) scans in adults at different stages of glycogen storage disease type III (GSDIII). Methods Fifteen patients aged 16 to 59 were examined on a 3T system. The examinations consisted of coronal and axial T1 weighted images or fat images from Dix...
Article
The field of translational research in Duchenne muscular dystrophy (DMD) has been transformed in the last decade by a number of therapeutic targets, mostly studied in ambulant patients. A paucity of studies focus on measures that capture the non-ambulant stage of the disease, and the transition between the ambulant and non-ambulant phase. In this p...
Article
Full-text available
Objective To assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year. Methods One hundred ninety-three patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, and 1-year assessments included adapted...
Article
Introduction/Background Upper limb function is fundamental for non-ambulant patients. In neuromuscular diseases, the impact of handgrip and key pinch progressive weakness on hand function is not described. This study aims to establish the relationships between hand strength and function in non-ambulant patients with Duchenne muscular dystrophy (DMD...
Article
Cardiomyopathy caused by lamin A/C gene (LMNA) mutations (hereafter referred as LMNA cardiomyopathy) is an anatomic and pathologic condition associated with muscular and electrical dysfunction of the heart, often leading to heart failure-related disability. There is currently no specific therapy available for patients that target the molecular path...
Article
Background The need for deeper understanding of Duchenne muscular dystrophy (DMD) natural history is supported by the rapid advances in translational research, the increase in clinical trials and outcome of recent studies. Aim Assess the natural history of DMD through a composite assessment tool encompassing ambulant and non-ambulant phases of the...
Article
Glycogen storage disease type III (GSDIII) is an autosomal recessive disorder caused by mutations in the AGL gene coding for the glycogen debranching enzyme. Current therapy is based on dietary adaptations but new preclinical therapies are emerging. The identification of outcome measures which are sensitive to disease progression becomes critical t...
Article
Background: The efficacy of enzyme replacement therapy (ERT) in patients at an advanced stage of Pompe disease has only been addressed in a few studies. Our objective was to assess the long term effects of ERT in a cohort of patients with severe Pompe disease. Methods: We identified patients from the French Pompe Registry with severe respiratory...
Article
Novel emerging therapies for Duchenne muscular dystrophy (DMD), such as antisense oligomer (AO) mediated exon skipping, have generated the need of understanding the natural history study of the targeted genotype subgroups. Most natural history studies are focused on ambulant subjects; therefore very little data exists on non-ambulant DMD. Specifica...
Article
Aim: To develop a patient-reported outcome measure (PROM) assessing upper limb function related to activities of daily living (ADL) that cannot be observed in a clinical setting, specifically for patients with Duchenne muscular dystrophy (DMD) across a wide age range, applicable in the different stages of the disease. Method: The developmental p...
Article
Glycogen storage disease type III is an inherited metabolic disorder characterized by liver and muscle impairment. This study aimed to identify promising muscle function measures for future studies on natural disease progression and therapeutic trials. The age-effect on the manual muscle testing (MMT), the hand-held dynamometry (HHD), the motor fun...
Article
Objective: To explore the value of nuclear magnetic resonance (NMR) and functional assessments for follow-up of ambulatory and nonambulatory patients with Duchenne muscular dystrophy (DMD). Methods: Twenty-five 53-skippable patients with DMD were included in this study; 15 were nonambulatory at baseline. All patients underwent clinical and funct...
Article
Full-text available
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/femal...
Article
Full-text available
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 mea...
Article
Full-text available
Background Wrist movements become impaired with disease progression in various neuromuscular disorders. With the development of new therapies, thorough measurement of muscle strength is crucial to document natural disease progression and to assess treatment efficacy. We developed a new dynamometer enabling wrist flexion and extension torque measure...
Article
Full-text available
Force and motion generated by skeletal muscle ultimately depends on the cyclical interaction of actin with myosin. This mechanical process is regulated by intracellular Ca(2+) through the thin filament-associated regulatory proteins i.e.; troponins and tropomyosin. Muscular dystrophies are a group of heterogeneous genetic affections characterized b...
Conference Paper
Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease for which treatments are being developed. There is a need to define reliable and reproducible criteria to evaluate neuromuscular function in order to assess their effects. The main aim of our study consists of a follow-up of the natural history of DM1 patients over 3 years. Here, base...
Conference Paper
Full-text available
Upper limb evaluation of patients with Duchenne Muscular Dystrophy is crucially important to evaluate efficacy of new treatments in non-ambulant patients. Adequate outcome measures are scarce for patients who have lost ambulation. In addition, longitudinal data demonstrating sensitivity to clinical evolution of outcome measures on a short term peri...
Conference Paper
Glycogen storage disease type 3 (GSD3) is an autosomal recessive disorder caused by mutations in the AGL gene coding for the glycogen debranching enzyme, which releases glucose from glycogen. Current therapy is primarily based on dietary modifications but pharmacological approaches are emerging. The pattern of muscle clinical involvement is poorly...
Article
Natural history studies in sporadic inclusion body myositis are of fundamental interest for future therapeutic trials. Previous works have demonstrated the particular relevance of knee extension strength in the follow-up of this disease. This work aimed to extend a preceding natural history over 9 months to a four year period. Thirteen patients wer...
Article
AimAn international Clinical Outcomes Group consisting of clinicians, scientists, patient advocacy groups, and industries identified a need for a scale to measure motor performance of the upper limb. We report the steps leading to the development of the Performance of the Upper Limb (PUL), a tool specifically designed for assessing upper limb funct...
Article
Spinal muscular atrophy (SMA) is recessive hereditary disease of the anterior horn cells caused by deletions or mutations of the SMN1 gene. The loss of muscle strength and function in these patients is gradual. The assessment of the upper limbs in non-ambulant neuromuscular patients remains a challenge and data is even scarcer for SMA patients. Our...
Article
In 2012 a group of international physiotherapists specializing in neuromuscular assessments devised a ClinRO to assess upper limb performance (PUL) for use in Duchenne muscular dystrophy (DMD). An exploratory Rasch analysis helped establish version one of the PUL although it was recognized at the time further analysis was required in a larger subse...
Article
Skeletal muscle diagnostic imaging is classically based on visual inspection of T1-weighted NMR images and interpretation of patterns of fatty infiltration. The existence of oedematous/inflammatory/necrotic lesions is subjectively appreciated on T2-weighted images, typically acquired with the STIR sequence to minimize fat confounding effects. Becau...
Article
Full-text available
Exon skipping therapy is an emerging approach in Duchenne Muscular Dystrophy (DMD). Antisense oligonucleotides that skip exon 51, 44, 45, and 53 are currently evaluated in clinical trials. Knowing the precise phenotype of potentially eligible patients is important for designing the clinical trials. It is generally believed that there are few if any...
Article
Myotonic dystrophy is the most common adult muscle dystrophy. In view of emerging therapies, which use animal models as a proof of principle, the development of reliable outcome measures for in vivo longitudinal study of mouse skeletal muscle function is becoming crucial. To satisfy this need, we have developed a device to measure ankle dorsi- and...
Article
Context: Recombinant human GH (rhGH) improves growth and body composition in glucocorticoid-treated children. Its effects on muscle strength are poorly evaluated. Objectives: Our objective was to evaluate rhGH effects on muscle strength in children receiving long-term glucocorticoid therapy; effects on height SD score (SDS) and body composition...
Article
Full-text available
Dilated cardiomyopathy (DCM) associates left ventricular dilatation and systolic dysfunction and is a major cause of heart failure and cardiac transplantation. LMNA gene encodes lamins A/C, proteins of the nuclear envelope. LMNA mutations cause DCM with conduction and/or rhythm defects. The pathomechanisms linking mutations to DCM remain to be eluc...
Data
CELF1 protein levels in WT and DMSXL mice. (A) Western blot analysis was performed on heart of 2-month-old DMSXL and WT littermate controls. (B) Proteins level were quantified by densitometric analysis using non-saturated exposures of three different membranes. Data are expressed as means ± standard deviation. (TIF)
Data
Comparison between the mouse Dmpk gene and the human DMPK transgene expression in transgenic mice. The ratio between the mouse and human genes was studied by qRT-PCR in homozygous and hemizygous DMSXL mice (A), or by Rinonuclear Protection Assay in hemizygous DM300 mice (B). H, heart; FC, frontal cortex; B whole brain; G, gastrocnemius; K, kidney;...
Data
DMPK sense and antisense transcripts form nuclear foci in DMSXL skeletal muscle. (A) Localization of sense and antisense DMPK was studied using 5′-cy3-(CAG)5 (recognizing sense transcripts in red) and 5′-Alexa 488-(CTG)5 (recognizing antisense transcripts in green) probes in the same experiment. (B) FISH and immunohistochemistry were performed on h...
Data
Expression of the human DMPK transgene in mice carrying different CTG repeat lengths. Expression of the human DMPK transgene was studied in heart of 2-month-old DMSXL and DM300 hemizygotes (n = 5 per group). a.u.: arbitrary units. Data are presented as means ± SEM (*p<0.05, Student's t test). (TIF)
Data
Splicing analysis in DMSXL mice. Alternative exon inclusions in mRNA transcripts were studied by RT-PCR in 2- and 4-month-old mice in tibialis anterior (A) and heart (B), and in various muscles from 2-month-old mice (C). Results were compared between DMSXL (n = 6) and WT (n = 6). Alternative exons studied are indicated as well as 18S (loading contr...
Data
DMPK sense and antisense transcripts form nuclear foci in DMSXL heart. (A) Localization of sense and antisense DMPK was studied using 5′-cy3 - (CAG)5 (recognizing sense transcripts in red) and 5′-Alexa 488- (CTG)5 (recognizing antisense transcripts in green) probes in the same experiment. (B) FISH and immunohistochemistry were performed on homozygo...
Data
DMPK antisense and sense transcripts form nuclear foci that co-localize with MBNL1 in human DM1 heart. (A) Detection of antisense and sense DMPK transcripts using 5′-cy3 -(CTG)5 (recognizing antisense transcripts in red) and 5′-cy3 -(CAG)5 (recognizing sense transcripts in red) probes. (B) FISH and immunohistochemistry were performed using MBNL1 an...
Article
Full-text available
Myotonic dystrophy type 1 (DM1) is caused by an unstable CTG repeat expansion in the 3'UTR of the DM protein kinase (DMPK) gene. DMPK transcripts carrying CUG expansions form nuclear foci and affect splicing regulation of various RNA transcripts. Furthermore, bidirectional transcription over the DMPK gene and non-conventional RNA translation of rep...
Article
Development of appropriate outcome measures that are able to measure both deterioration and therapeutic effectiveness across the spectrum of severity in dystrophinopathies is complex. A multi-disciplinary international Clinical Outcomes Group consisting of clinicians, scientists, and patient advocacy groups specifically identified a need for a scal...
Article
Mutations of LMNA gene give rise to a range of muscular dystrophies associated with dilated cardiomyopathy (DCM) and conduction and/or rhythm defects. LMNA encodes lamin A/C, nuclear envelope proteins that form a meshwork beneath the inner nuclear membrane. The pathomechanisms linking LMNA mutations to muscular and cardiac diseases remain to be elu...
Article
Full-text available
A-type lamins A and C are nuclear intermediate filament proteins in which mutations have been implicated in multiple disease phenotypes commonly known as laminopathies. A few studies have implicated sumoylation in the regulation of A-type lamins. Sumoylation is a post-translational protein modification that regulates a wide range of cellular proces...
Article
Full-text available
Background Children with growth retardation or short stature generally present with lower strength than children of the same chronological age. The aim of the study was to establish if strength was dependent on variables related to stature in a population of healthy children and to propose practical predictive models for the muscle functions tested...
Article
There are currently no effective treatments to restore the muscle function in sporadic inclusion body myositis. Natural history studies of this disease are scarce. The goal of this study consisted in defining the functional pattern of patients with sporadic inclusion body myositis and to follow its change over a 9-month period to determine the most...
Article
Full-text available
The LMNA gene encodes lamin A/C intermediate filaments that polymerize beneath the nuclear membrane, and are also found in the nucleoplasm in an uncharacterized assembly state. They are thought to have structural functions and regulatory roles in signaling pathways via interaction with transcription factors. Mutations in LMNA have been involved in...
Article
Dominant inherited Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy type 1B are due to mutations in the LMNA gene encoding lamin A/C and present similar life-threatening cardiac disease, the early diagnosis of which lacks reliable biomarkers. Glutathione depletion characterizes subjects with cardiac diseases of non-genetic aetio...
Article
Les arythmies ventriculaires gauches représentent une des principales causes de décès chez les patients atteint de la Dystrophie Musculaire de Duchenne (DMD). Dans le muscle squelettique, nous avons mis évidence une augmentation de la s-nytrosylation du canal calcique de type 1 du réticulum sarcoplasmique (RS), le récepteur à la ryanodine (RyR1), à...
Article
Full-text available
The LMNA gene encodes lamins A and C, two intermediate filament-type proteins that are important determinants of interphase nuclear architecture. Mutations in LMNA lead to a wide spectrum of human diseases including autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD), which affects skeletal and cardiac muscle. The cellular mechanisms by...
Article
Skeletal muscle can bear a high load at constant length, or shorten rapidly when the load is low. This force-velocity relationship is the primary determinant of muscle performance in vivo. Here we exploited the quasi-crystalline order of myosin II motors in muscle filaments to determine the molecular basis of this relationship by X-ray interference...