Philippe Corcia

Philippe Corcia
University of Tours | UFR · ALS Center, CHRU Bretonneau, TOurs

About

363
Publications
35,975
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7,758
Citations
Citations since 2016
153 Research Items
5540 Citations
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201620172018201920202021202202004006008001,000
201620172018201920202021202202004006008001,000
201620172018201920202021202202004006008001,000

Publications

Publications (363)
Article
Background: Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative rare disease that a􀀀ects motor neurons in the brain, brainstem, and spinal cord, resulting in progressive weakness and atrophy of voluntary skeletal muscles. Although much has been achieved in understanding the disease pathogenesis, treatment options are limited, and in...
Preprint
Full-text available
Objective Genetic variation in the neurofilament heavy chain gene ( NEFH ) has been convincingly linked to the pathogenesis of multiple neurodegenerative diseases, however, the relationship between NEFH mutations and ALS susceptibility has not been robustly explored. We therefore wanted to determine if genetic variants in NEFH modify ALS risk. Met...
Preprint
Full-text available
Caveolin-1 and Caveolin-2 (CAV1 and CAV2) are proteins associated with intercellular neurotrophic signalling. There is converging evidence that CAV1 and CAV2 (CAV1/2) genes have a role in ALS. Disease-associated variants have been identified within CAV1/2 enhancers, which reduce gene expression and lead to disruption of membrane lipid rafts. Using...
Article
Currently, only four molecules can be prescribed for amyotrophic lateral sclerosis (ALS), of which only one is approved worldwide for this indication, riluzole. Although progress in the therapeutic field remains unsatisfactory, we have to notice that genetics have undergone impressive improvements over the last three decades and, by extension, our...
Preprint
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Background Given the large genetic heterogeneity in Amyotrophic Lateral Sclerosis (ALS), it seems likely that genetic subgroups may benefit differently from treatment. An exploratory meta-analysis identified that patients homozygous for the C-allele at SNP rs12608932, a single nucleotide polymorphism in the gene UNC13A, had a statistically signific...
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative syndrome. In up to 20% of cases, a family history is observed. Although Mendelian disease gene variants are found in apparently sporadic ALS, genetic testing is usually restricted to those with a family history or younger patients with sporadic disease. With the advent of ther...
Article
Full-text available
Background Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative rare disease that affects motor neurons in the brain, brainstem, and spinal cord, resulting in progressive weakness and atrophy of voluntary skeletal muscles. Although much has been achieved in understanding the disease pathogenesis, treatment options are limited, and in...
Article
Résumé Introduction Les syndromes de la traversée thoraco-brachiale (STTB) dits neurologiques sont dominés par les formes subjectives. Cette étude ne concerne que les rares formes objectives liées à une compression nerveuse proximale dans la traversée thoraco-brachiale, avec la présence de signes déficitaires neurologiques moteurs (amyotrophie des...
Article
There is currently no diagnostic or prognostic biomarker available in clinical practice for Amyotrophic Lateral Sclerosis (ALS). The objective of this study was to monitor a combination of various inflammatory markers, lipids, and apolipoprotein alterations in ALS patients at the time of diagnosis, to assess their role as early diagnostic or progno...
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder that still lacks an efficient therapy. The barriers between the central nervous system (CNS) and the blood represent a major limiting factor to the development of drugs for CNS diseases, including ALS. Alterations of the blood-brain barrier (BBB) or blood-spinal cord ba...
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Diverse biomarkers and pathological alterations have been found in muscle of patients with Amyotrophic lateral sclerosis (ALS), but the relation between such alterations and dysfunction in energetic metabolism remains to be investigated. We established the metabolome of muscle and serum of ALS patients and correlated these findings with the clinica...
Article
Introduction: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that lacks an effective treatment. Aggregates of the TAR DNA-binding protein-43 (TDP-43) are observed in 97% of all ALS cases, thus making this protein a major therapeutic target in ALS. . Areas covered: The authors describe the major cellular functions of TDP...
Article
Background A rare cause of scapular winging is rhomboid muscle paralysis secondary to dorsal scapular nerve (DSN) neuropathy. This paralysis causes winging of the medial border of the scapula with lateral rotation of its inferior angle. We report a series of 4 clinical cases of isolated DSN compression and the results of a specific rehabilitation p...
Article
Introduction: Neurogenic thoracic outlet syndromes (TOS) are dominated by the nonspecific forms. This study focuses only on the rarer true forms related to proximal nerve compression in the thoracic outlet, with the presence of motor (atrophy of the hand’s intrinsic muscles) and/or sensory (hypoesthesia in the territory of the medial antebrachial c...
Preprint
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Background Humans are thought to be more susceptible to neurodegeneration than equivalently-aged primates. It is not known whether this vulnerability is specific to anatomically-modern humans or shared with other hominids. The contribution of introgressed Neanderthal DNA to neurodegenerative disorders remains uncertain. It is also unclear how commo...
Article
Background Serratus anterior (SA) palsy following mechanical injury to the long thoracic nerve (LTN) is the most common cause of scapular winging. This study aimed to identify the factors influencing the outcome of neurolysis of the distal segment of the LTN. We hypothesized that poor results are due to duration before surgery and to persistent sca...
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The ubiquitin pathway regulates the function of many proteins and controls cellular protein homeostasis. In recent years, it has attracted great interest in neurodevelopmental and neurodegenerative diseases. Here, we have presented the first review on the roles of the 9 proteins of the HECT E3 ligase NEDD4 subfamily in the development and function...
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Full-text available
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide a...
Article
Full-text available
Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA). Objective: To assess the feasibility of clinical stu...
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The human tear film is at the interface between the ocular surface and the external environment. Although investigation has been hindered by its small volume, improvements in preanalytical and analytical methods have allowed the omics approach to represent an innovative biomarker search strategy. There is still a significant lack of standardization...
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Full-text available
There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwi...
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Full-text available
Amyotrophic lateral sclerosis (ALS) is a complex disease that leads to motor neuron death. Despite heritability estimates of 52%, genome-wide association studies (GWASs) have discovered relatively few loci. We developed a machine learning approach called RefMap, which integrates functional genomics with GWAS summary statistics for gene discovery. W...
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Full-text available
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 indi...
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 indi...
Article
Background There is an urgent unmet need for new therapies in amyotrophic lateral sclerosis. In a clinical study with healthy volunteers, levosimendan, a calcium sensitiser, was shown to improve neuromechanical efficiency and contractile function of the human diaphragm. We aimed to evaluate the safety and efficacy of oral levosimendan in people wit...
Article
We read with great interest the letter of Drs Gazulla and collaborators, who suggested that the continuum between primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) is not straightforward.1 They indicated that PLS can be associated to other central nervous system disorders related to known or unknown rare mutations.
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Background Malnutrition and weight loss are negative prognostic factors for survival in patients with amyotrophic lateral sclerosis (ALS). However, energy expenditure at rest (REE) is still not included in clinical practice, and no data are available concerning hypometabolic state in ALS. Objective To evaluate in a referral cohort of patients with...
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Full-text available
Frontotemporal involvement has been extensively investigated in amyotrophic lateral sclerosis (ALS) but remains relatively poorly characterized in other motor neuron disease (MND) phenotypes such as primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), spinal muscular atrophy (SMA), spinal bulbar muscular atrophy (SBMA), post poliomy...
Article
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated and treatable disease that may be associated with various systemic conditions. Our objective is to describe the clinical, electrophysiological and pathological data of a series of patients with both CIDP and hemopathy. In this retrospective study, we analyzed 21...
Article
Background and purpose: Primary lateral sclerosis (PLS) is a motor neuron disorder characterized by a pure upper motor neuron degeneration in the bulbar and spinal regions. The key difference with amyotrophic lateral sclerosis (ALS) is the lower motor neuron system integrity. Despite important literature on this disease, the pathophysiology of PLS...
Article
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting the upper and lower motor neurons. A key clinical feature of ALS is the absence of accurate, early-stage diagnostic indicators. ‘Split-hand syndrome’ was first described in ALS at the end of the last century and a considerable body of literature suggests that...
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Full-text available
Primary Lateral Sclerosis (PLS) is an uncommon motor neuron disorder. Despite the well-recognisable constellation of clinical manifestations, the initial diagnosis can be challenging and therapeutic options are currently limited. There have been no recent clinical trials of disease-modifying therapies dedicated to this patient cohort and awareness...
Article
Mohassel et al. provide unprecedented dichotomy of consequences on sphingolipid biosynthesis between pathogenic variants in the SPTLC1 gene, responsible for either amyotrophic lateral sclerosis (ALS) or hereditary sensory and autonomic neuropathy type 1 (HSAN1). Normalization of sphingolipid levels by siRNA selectively targeting the ALS mutant alle...
Article
Primary Lateral Sclerosis (PLS) is a motor neuron disorder characterized by a pure UMN degeneration in bulbar and spinal regions. The key difference with Amyotrophic Lateral Sclerosis (ALS) is the lower motor neuron system integrity. Despite important literature on this disease, pathophysiology of PLS remains unknown and the link with ALS still bal...
Article
Full-text available
The aim of this study was to evaluate the kynurenine pathway (KP) and amino acids profile, using mass spectrometry, in the cerebrospinal fluid (CSF) of 42 amyotrophic lateral sclerosis (ALS) patients at the diagnosis and 40 controls to detect early disorders of these pathways. Diagnostic and predictive ability (based on weight loss, forced vital ca...
Article
Clinically, ALS phenotypes depend on the areas of the body that are affected, the different degrees of involvement of upper and lower motor neurons, the degrees of involvement of other systems, particularly cognition and behavior, and rates of progression. Phenotypic variability of ALS is characteristic and can be declined on the distribution of mo...
Article
Résumé Introduction Les neuropathies proximales du nerf médian (NM) sont responsables d’1 % des syndromes canalaires du membre supérieur. La littérature rapporte deux tableaux cliniques en fonction de la localisation du processus compressif : le syndrome du rond pronateur (SRP) et le syndrome du nerf interosseux antérieur (SNIOA). Hypothèse Il n’...
Article
Objective Mutations in superoxide dismutase 1 gene ( SOD1) , encoding copper/zinc superoxide dismutase protein, are the second most frequent high penetrant genetic cause for amyotrophic lateral sclerosis (ALS) motor neuron disease in populations of European descent. More than 200 missense variants are reported along the SOD1 protein. To limit the p...
Preprint
Full-text available
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability of around 50%. DNA methylation patterns can serve as biomarkers of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide ass...
Preprint
Full-text available
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a life-time risk of 1 in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry GWAS in ALS including 29,612 ALS patients and 122,656 controls which identified 15 risk loci in ALS. When combined with 8,953 whole-genome sequenced indivi...
Preprint
Full-text available
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a life-time risk of 1 in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry GWAS in ALS including 29,612 ALS patients and 122,656 controls which identified 15 risk loci in ALS. When combined with 8,953 whole-genome sequenced indivi...
Article
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by death of motor neurons in the cortex and the spinal cord. This loss of motor neurons causes progressive weakness and amyotrophy. To date, the median duration of survival in patients with ALS, from first symptoms to death, is estimated to be 36 months. Currentl...
Article
Full-text available
Protein aggregates in affected motor neurons are a hallmark of amyotrophic lateral sclerosis (ALS), but the molecular pathways leading to their formation remain incompletely understood. Oxidative stress associated with age, the major risk factor in ALS, contributes to this neurodegeneration in ALS. We show that several genes coding for enzymes of t...
Article
Background: Proximal median nerve (MN) neuropathy represents 1% of upper-limb compressive neuropathies. The literature reports two clinical presentations, depending on the location of the entrapment: pronator teres (PT), and anterior interosseous nerve (AIN) syndrome. Hypothesis: There is no correlation between symptoms and location of proximal com...
Article
Objectives To determine whether the familial clustering of amyotrophic lateral sclerosis (ALS) cases and the phenotype of the disease may help identify the pathogenic genes involved. Methods We conducted a targeted next-generation sequencing analysis on 235 French familial ALS (FALS), unrelated probands to identify mutations in 30 genes linked to...
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Full-text available
Objective The role of Survival of Motor Neuron gene (SMN) in Amyotrophic lateral sclerosis (ALS) is unclear, with several conflicting reports. A decisive result on this topic is needed, given that treatment options are available now for SMN deficiency. Methods In this largest multicentre case control study to evaluate the effect of SMN1 and SMN2 c...
Article
Full-text available
Monoclonal gammopathy is encountered quite frequently in the general population. This type of hematological abnormality may be mild, referred to as ‘monoclonal gammopathy of undetermined significance’ (MGUS) or related to different types of hematological malignancies. The association of a peripheral neuropathy with monoclonal gammopathy is also fai...
Article
Sleep-disordered breathing and sleep-related symptoms are frequent in patients with severe amyotrophic lateral sclerosis (ALS). We aimed to describe sleep quality, sleep structure, and the occurrence of sleep-disordered breathing in patients with early ALS, at the time of initial evaluation in a tertiary care center. Sleep-related symptoms were col...
Article
With the exception of rare, juvenile-onset, autosomal recessive cases, primary lateral sclerosis (PLS) has long been considered an exclusively sporadic motor neuron disease. However, the identification of PLS cases within pedigrees with familial amyotrophic lateral sclerosis (ALS), together with the clinical and neuropathological overlap with other...
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the progressive death of both upper and lower motor neurons. The disease presents a poor prognosis, and patients usually die 2-5 years after the onset of symptoms. The hallmark of this disease is the presence of phosphorylated and ubiquitinated aggregates containing trans-...
Article
Full-text available
Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive loss of motor neurons. Patients usually die 3–5 years after diagnosis from respiratory failure. Several studies investigated the role of vitamin D as a biomarker or a therapeutic option for ALS patients. To clarify the scientific eviden...
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Full-text available
A change in our current approach toward drug development is required to improve the likelihood of finding effective treatment for patients with amyotrophic lateral sclerosis (ALS). The aim of the Treatment Research Initiative to Cure ALS (TRICALS) is to extend the collective effort with industry and consolidate drug development paths. TRICALS has b...
Article
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Increasingly, repeat expansions are being identified as part of the complex genetic architecture of amyotrophic lateral sclerosis. To date, several repeat expansions have been genetically associated with the disease: intronic repeat expansions in C9orf72, polyglutamine expansions in ATXN2 and polyalanine expansions in NIPA1. Together with previousl...
Article
Full-text available
Metabolomics studies performed in patients with amyotrophic lateral sclerosis (ALS) reveal a set of distinct metabolites that can shed light on the pathological alterations taking place in each individual. Metabolites levels are influenced by disease status, and genetics play an important role both in familial and sporadic ALS cases. Metabolomics a...
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, but its definitive diagnosis delays around 12 months. Although the research is highly active in the biomarker field, the absence of specific biomarkers for diagnosis contributes to this long delay. Another strategy of biomarker identification based on less specific but sen...
Article
Cytoplasmic aggregation of TAR-DNA binding protein (TDP-43) in Amyotrophic Lateral Sclerosis (ALS) and fronto-temporal lobar dementia (FTLD) is associated with post-translational modifications (PTM) and delocalization. Studies on postmortem brains of ALS and FTLD patients showed the existence of TDP-43 fragments that end at position N291. We report...
Article
Background: Neutrophil-to-lymphocyte ratio (NLR) is increased and associated with overall survival (OS) in inflammatory diseases including dermatomyositis/polymyositis (DM/PM) and many cancers. The risk of cancer is increased with DM/PM especially in adults > 50 years old. Objectives: To determine whether high NLR is associated with an increased...