المؤلفون: Faggianelli, Florent, Witjas, Tatiana, Azulay, J-P, Benatru, Isabelle, Hubsch, Cécile, Anheim, Mathieu, Moreau, Caroline, Hainque, Elodie, Drapier, Sophie, Jarraya, Béchir, Laurencin, Chloé, Guehl, Dominique, Hopes, Lucie, Brefel-Courbon, Christine, Tir, Melissa, Marques, Ana, Rouaud, Tiphaine, Maltete, David, Giordana, Caroline, Baumstarck, Karine, Rascol, Olivier, Corvol, Jean Christophe, Rolland, Anne-Sophie, Devos, David, Eusebio, Alexandre, PREDISTIM study group, Defebvre, Luc, Carriere, Nicolas, Grolez, Guillaume, Baille, Gillaume, Kreisler, Jean-Pierre Pruvo, Leclerc, Pr, Lopes, Renaud, Viard, Romain, Kuchcinski, Gregory, Dumont, Julien, Dujardin, Kathy, Delliaux, M, Brion, M, Touzet, Gustavo, Reyns, Nicolas, Delval, Arnaud, Santraine, Valerie, Pleuvret, Marie, Dautrevaux, Nolwen, Laugeais, Victor, Coeffet, Morgane, Ouk, Thavarak, Potey, Camille, Leclercq, Celine, Gers, Elise, Corvol, Jean-Christophe, Vidailhet, Marie, Welter, Marie-Laure, Lacomblez, Lucette, Grabli, David, Roze, Emmanuel, Worbe, Yulia, Delorme, Cécile, You, Hana, Ihle, Jonas, Guimeraes-Costa, Raquel, Cormier-Dequaire, Florence, Méneret, Aurélie, Hartmann, Andréas, Mariani, Louise-Laure, Lehericy, Stéphane, Czernecki, Virginie, Pineau, Fanny, Bozon, Frédérique, Huiban, Camille, Benchetrit, Eve, Karachi, Carine, Navarro, Soledad, Cornu, Philippe, Welaratne, Arlette, Dongmo-Kenfack, Carole, Mantisi, Lise, Jarry, Nathalie, Aix, Sophie, Lefort, Carine, Damier, Philippe, Derkinderen, Pascal, Corbille, Anne-Gaelle, Calvier-Auffray, Elisabeth, Rocher, Madame Laetitia, Deruet, Madame Anne-Laure, Sylvie, Raoul, Vincent, Roualdes, Séverine, Le Dily, Debilly, Berangere, Durif, Franck, Derost, Philippe, Beal, Charlotte, Chassain, Carine, Delaby, Laure, Vidal, Tiphaine, Lemaire, Jean Jeacques, Rieu, Isabelle, Durand, Elodie, Fluchère, Frédérique, Grimaldi, Stephan, Girard, Nadine, Delfini, Marie, Carron, Romain, Regis, Jean, Spatola, Giorgio, Magnaudet, Camille, Solène, Ansquer, Olivier, Colin, Houeto, J L, Remy, Guillevin, Anne, Fradet, Manssouri, Anziza, Sophie, Blondeau, Philippe, Richard, Philippe, Cam, Philippe, Page, Benoit, Bataille, Emilie, Rabois, Annie, Guillemain, Leh, Frédérique, Bonnet, Alexandre, Vérin, Marc, Ferré, Jean-Christophe, Houvenaghel, Jean Francois, Haegelen, Claire, Kestens, Francoise, Ory, Solenn, Burbaud, Pierre, Damon-Perriere, Nathalie, Meissner, Wassilios, Tison, Francois, Bannier, Stéphanie, Krim, Elsa, Molinier-Blossier, Sandrine, Ollivier, Morgan, Lacoste, Marion, Auzou, Nicolas, Bonnet, Marie, Cuny, Emmanuel, Engelhardt, Julien, Branchard, Olivier, Huet, Clotilde, Blanchard, Julie, Magne, Fabienne Ory, Moreau, Marion Simonetta, Arbus, Christophe, Bonnevilleet, Fabrice, Lotterie, Jean Albert, Sarrail, Marion, Chaynes, Patrick, Caire, Francois, Harroch, Estelle, Lefaucheur, Romain, Fetter, Damien, Magne, Nicolas, Bioux, Sandrine, Loubeyre, Maud, Bliaux, Evangéline, Pouliquen, Dorothée, Derrey, Stéphane, Vernon, Linda, Ziegler, Frédéric, Lagha-Boukbiza, Ouhaid, Tranchant, Christine, Gebus, Odile, Montaut, Solveig, Kremer, Stéphane, Longato, Nadine, Phillips, Clélie, Voirin, Jimmy, Santin, Marie desNeiges, Chaussemy, Dominique, Mengin, Amaury, Marsé, Claire, Mondot, Lydiane, Giordana, Bruno, Kardous, Robin, Bailet, Bernadette, Joly, Héloise, Fontaine, Denys, Leplus, Aurélie, Faustini, Amélie, Ferrier, Vanessa, Krystkowiak, Pierre, Constans, Jean-Marc, Wannepain, Sandrine, Seling, Audrey, Lefranc, Michel, Blin, Stéphanie, Schuler, Béatrice, Thobois, Stephane, Danaila, Teodor, Berthezene, Yves, Ameli, Roxana, Klinger, Helene, Polo, Gustavo, Mertens, Patrick, Nunes, A, Metereau, Elise, Frismand, Solène, Schmitt, Emmanuelle, Meyer, Mylène, Dillier, Céline, Colnat, Sophie, Chatelain, Anne, Brandel, Jean- Philippe, Karsenti, Patte, Lebouteux, Marie, Ziegler, Marc, Delmaire, Christine, Savatowky, Julien, Vrillac, Juliette, Nakache, Claire, Belamri, Vincent D’HardemareLhaouas, Mesnage, Valérie, Bonnet, Cécilia, Correa, Jarbas, Junior, Lino, Decrocq, Camille, Boulin, Anne, Auliac-Condette, Stéphanie, Gratieux, Julie, Terfaia, Dilanda, Gardel, Bérénice, Lopez, Delphine, Prette, Lydie, Sacko, Fantoumata, Ziz, Catherine, Gay, David, Bonicel, Robin, Mountassir, Fouzia El, Fischer, Clara, Mangin, Jean-Francois, Chupin, Marie, Cointepas, Yann, Accart, Bertrand, Gelé, Patrick, Fievet, Florine, Chabel, Matthieu, Derenaucourt, Virginie, Facon, Loïc, Njosse, Yanick Tchantchou, Deplanque, Dominique, Duhamel, Alain, Djemmane, Lynda, Duflot, Florence, Chouiki, Hajar

مصطلحات موضوعية: Movement disorders

الوصف: Background NMF are currently poorly evaluated in therapeutic decisions. A quantification of their severity would facilitate their integration. The objective of this study was to validate an autoquestionnaire evaluating the severity of non-motor fluctuations (NMF) in Parkinson’s disease (PD). Methods Patients with PD were included in presurgical situation for deep brain stimulation of subthalamic nuclei. They participated in the PREDISTIM cohort (a study evaluating the predictive factors for therapeutic response of subthalamic stimulation in PD) in 17 centres in France. Our questionnaire, resulting from previous phases of development, included 11 non-motor symptoms (NMS). Their severity ranged from 0 to 10 and was assessed in OFF and then ON-Dopa to study their fluctuations. Results 310 patients were included, of whom 98.8% had NMS and 98.0% had NMF. Each NMS was significantly improved by L-Dopa (decrease in severity score ranging from 43.1% to 69.9%). Fatigue was the most frequent and most severe NMS. NMS were considered more bothersome than motor symptoms by 37.5% of patients in OFF-Dopa and 34.9% in ON-Dopa. Conclusions This is the first questionnaire allowing a real-time quantification of the severity of NMS and their fluctuation with levodopa. It was able to confirm and measure the effect of L-dopa and show differences according to the patients and the NMS. It differs from other questionnaires by its measurement at a precise moment of the severity of the NMS, allowing its use during pretherapeutic assessments. Our questionnaire has been validated to measure the severity of NMF. It will be able to quantify the non-motor effect of anti-parkinsonian treatments and could facilitate the integration of NMF in therapeutic decisions.

وصف الملف: text/html

العلاقة: http://jnnp.bmj.com/cgi/content/short/95/7/656Test; http://dx.doi.org/10.1136/jnnp-2023-332551Test

الإتاحة: https://doi.org/10.1136/jnnp-2023-332551Test
http://jnnp.bmj.com/cgi/content/short/95/7/656Test

المؤلفون: Jackson, Holly, Anzures-Cabrera, Judith, Taylor, Kirsten I, Pagano, Gennaro, Investigators, PASADENA, Group, Prasinezumab Study, Altendorf, Claudia, Anandan, Chareyna, Andrews, Giulia, Ansquer, Solène, Arrouasse, Raphaele, Aslam, Sana, Azulay, Jean-Philippe, Baker, Jeanette, Martinez, Ernest Balaguer, Barbu, Shadi, Bardram, Kara, Bega, Danny, Marco, Helena Bejr-Kasem, Benatru, Isabelle, Benchetrit, Eve, Bernhard, Felix, Besharat, Amir, Bette, Sagari, Bichon, Amelie, Billnitzer, Andrew, Blondeau, Sophie, Boraud, Thomas, Borngräber, Freiderike, Boyd, James, Brockmann, Kathrin, Brodsky, Matthew, Brown, Ethan, Bruecke, Christof, Calvas, Fabienne, Canelo, Monica, Carbone, Federico, Carroll, Claire, Fernandez, Laura Casado, Cassé-Perrot, Catherine, Castrioto, Anna, Catala, Helene, Chan, Justine, Cheriet, Samia, Ciabarra, Anthony, Classen, Joseph, Coleman, Juliana, Coleman, Robert, Compta, Yaroslau, Corbillé, Anne-Gaëlle, Corvol, Jean-Christophe, Cosgaya, Mariana, Dahodwala, Nabila, Damier, Philippe, David, Elodie, Davis, Thomas, Dean, Marissa, Debilly, Berengere, DeGiorgio, Janell, Deik, Andres, Delaby, Laure, Delfini, Marie-Helene, Derkinderen, Pascal, Derost, Philipp, de Toledo, Maria, Deuel, Lisa, Diaz-Hernandez, Ann Marie, Dietiker, Cameron, Dimenshteyn, Karina, Dotor, Julio, Durif, Franck, Ebentheuer, Jens, Eggert, Karla Maria, Madueño, Sara Eichau, Eickhoff, Claudia, Ellenbogen, Aaron, Ellmerer, Philipp, Vazquez, Ines Esparragosa, Eusebio, Alexandre, Ewert, Siobhan, Fang, John, Feigenbaum, Danielle, Fluchere, Frederique, Foubert-Samier, Alexandra, Fournier, Marie, Fradet, Anne, Fraix, Valerie, Frank, Samuel, Fries, Franca, Galitzky, Monique, Pérez, Marisol Gallardó, Moreno, Jose Manuel García, Gasca, Carmen, Gasser, Thomas, Gibbons, Joyce, Giordana, Caroline, Martinez, Alicia Gonzalez, Goodman, Ira, Gorospe, Arantza, Goubeaud, Marie

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Psychology, Biomedical Imaging, Parkinson's Disease, Brain Disorders, Clinical Research, Aging, Neurosciences, Neurodegenerative, Clinical Trials and Supportive Activities, Neurological, PASADENA Investigators, Prasinezumab Study Group, Dat-SPECT imaging, MDS-UPDRS, PASADENA, PPMI, Parkinson’s disease, disease stage, progression predictors, ridge regression, Cognitive Sciences, Biological psychology

الوصف: Currently, no treatments available for Parkinson's disease (PD) can slow PD progression. At the early stage of the disease, only a subset of individuals with PD progress quickly, while the majority have a slowly progressive form of the disease. In developing treatments that aim to slow PD progression, clinical trials aim to include individuals who are likely to progress faster, such that a treatment effect, if one exists, can be identified easier and earlier. The aim of the present study was to identify baseline predictors of clinical progression in early PD. We analyzed 12-month data acquired from the PASADENA trial Part 1 (NCT03100149, n = 76 participants who were allocated to the placebo arm and did not start symptomatic therapy) and the Parkinson's Progression Markers Initiative (PPMI) study (n = 139 demographically and clinically matched participants). By using ridge regression models including clinical characteristics, imaging, and non-imaging biomarkers, we found that Hoehn and Yahr stage and dopamine transporter single-photon emission computed tomography specific binding ratios (Dat-SPECT SBR) in putamen ipsilateral to the side of motor symptom onset predicted PD progression at the early stage of the disease. Further studies are needed to confirm the validity of these predictors to identify with high accuracy individuals with early PD with a faster progression phenotype.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6bh4v1crTest

المؤلفون: Pagano, Gennaro, Boess, Frank G, Taylor, Kirsten I, Ricci, Benedicte, Mollenhauer, Brit, Poewe, Werner, Boulay, Anne, Anzures-Cabrera, Judith, Vogt, Annamarie, Marchesi, Maddalena, Post, Anke, Nikolcheva, Tania, Kinney, Gene G, Zago, Wagner M, Ness, Daniel K, Svoboda, Hanno, Britschgi, Markus, Ostrowitzki, Susanne, Simuni, Tanya, Marek, Kenneth, Koller, Martin, Sevigny, Jeff, Doody, Rachelle, Fontoura, Paulo, Umbricht, Daniel, Bonni, Azad, Investigators, PASADENA, Group, Prasinezumab Study, Altendorf, Claudia, Anandan, Chareyna, Andrews, Giulia, Ansquer, Solène, Arrouasse, Raphaele, Aslam, Sana, Azulay, Jean-Philippe, Baker, Jeanette, Martinez, Ernest Balaguer, Barbu, Shadi, Bardram, Kara, Bega, Danny, Marco, Helena Bejr-Kasem, Benatru, Isabelle, Benchetrit, Eve, Bernhard, Felix, Besharat, Amir, Bette, Sagari, Bichon, Amelie, Billnitzer, Andrew, Blondeau, Sophie, Boraud, Thomas, Borngräber, Freiderike, Boyd, James, Brockmann, Kathrin, Brodsky, Matthew, Brown, Ethan, Bruecke, Christof, Calvas, Fabienne, Canelo, Monica, Carbone, Federico, Carroll, Claire, Fernandez, Laura Casado, Cassé-Perrot, Catherine, Castrioto, Anna, Catala, Helene, Chan, Justine, Cheriet, Samia, Ciabarra, Anthony, Classen, Joseph, Coleman, Juliana, Coleman, Robert, Compta, Yaroslau, Corbillé, Anne-Gaëlle, Corvol, Jean-Christophe, Cosgaya, Mariana, Dahodwala, Nabila, Damier, Philippe, David, Elodie, Davis, Thomas, Dean, Marissa, Debilly, Berengere, DeGiorgio, Janell, Deik, Andres, Delaby, Laure, Delfini, Marie-Helene, Derkinderen, Pascal, Derost, Philipp, de Toledo, Maria, Deuel, Lisa, Diaz-Hernandez, Ann Marie, Dietiker, Cameron, Dimenshteyn, Karina, Dotor, Julio, Durif, Franck, Ebentheuer, Jens, Eggert, Karla Maria, Madueño, Sara Eichau, Eickhoff, Claudia, Ellenbogen, Aaron, Ellmerer, Philipp, Vazquez, Ines Esparragosa

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Neurodegenerative, Parkinson's Disease, Clinical Research, Neurosciences, Aging, Clinical Trials and Supportive Activities, Brain Disorders, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Neurological, PASADENA Investigators, Prasinezumab Study Group, MDS-UPDRS = Movement Disorder Society—Unified Parkinson's Disease Rating Scale, Parkinson's disease, Phase II clinical trial, alpha-synuclein, disease modification treatments, disease progression, monoclonal antibodies, prasinezumab, Psychology, Clinical sciences, Biological psychology

الوصف: Background: Currently available treatments for Parkinson's disease (PD) do not slow clinical progression nor target alpha-synuclein, a key protein associated with the disease. Objective: The study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD. Methods: The PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1,500 or 4,500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40-80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis ≤2 years; having bradykinesia plus one other cardinal sign of PD (e.g., resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naïve or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinson's Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naïve and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations. Results: Of the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. Mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naïve PASADENA cohorts (MDS-UPDRS sum of Parts I + II + III [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naïve and 36.4% on MAO-B inhibitor) showed a similar severity in MDS-UPDRS scores (e.g., MDS-UPDRS sum of Parts I + II + III [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve). Conclusions: The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD. Trial Registration: NCT03100149.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2tv8r5dgTest

المؤلفون: Corbillé, Anne-Gaëlle

مرشدي الرسالة: Nantes, Derkinderen, Pascal, Neunlist, Michel

مصطلحات موضوعية: Alpha-synucléine

الوصف: La maladie de Parkinson (MP) est une maladie du mouvement caractérisée par une neurodégénérescence de la substance noire et la présence d’inclusions d’α- synucléine (α-syn), les corps de Lewy, dans les neurones survivants. Elle se manifeste aussi par des symptômes non moteurs, dont certains, comme la constipation, surviennent précocement. La découverte que le système nerveux entérique (SNE) est fréquemment touché par la pathologie de Lewy a conduit à envisager que le tissu digestif puisse être source d'un biomarqueur précoce de la MP et que le processus pathologique de la maladie puisse s’initier dans le tube digestif pour gagner ensuite le système nerveux central par un mécanisme de type prion. L’objectif de mon travail de thèse a donc été d’optimiser la détection de l’α-syn dans le tube digestif et de comparer les propriétés de l’α-syn entérique et cérébrale. Nous avons montré que les méthodes immunohistochimiques (IHC) visant à détecter l’α-syn dans le tissu gastro-intestinal inclus en paraffine étaient limitées par des aspects techniques, mais qu’elles permettaient sur des coupes coliques avec paroi entière de détecter l’α-syn pathologique de façon performante. Puis, en utilisant une approche biochimique, nous avons montré que l’α-syn entérique native n’avait probablement pas la même tendance à s’assembler que dans le cerveau et que son niveau d’expression n’était pas modifié dans la MP. Nos travaux sont prometteurs pour la mise au point de marqueurs histologiques entériques de la MP et suggèrent une propension différente entre l’α-syn entérique et celle du cerveau à devenir pathogène.
Parkinson's disease (PD) is a movement disorder characterized by neurodegeneration in the substantia nigra and the presence of inclusions of α-synuclein (α- syn) aggregates, termed Lewy bodies, in surviving neurons. Patients may also exhibit various non-motor symptoms, such as constipation, which occur several years before the onset of motor symptoms. The discovery that the enteric nervous system (ENS) is frequently affected by Lewy pathology has led to consider the digestive tissue as a potential source for a specific PD biomarker and even to suggest that the pathological process (pathogenic α-syn) could be initiated in the gut and be propagated to central nervous system by a prion-like mechanism. The aim of my thesis was therefore (i) to optimize the detection of α-syn in the digestive tract in both physiological and pathological conditions and (ii) to compare the properties of α-syn enteric and nervous system central. In the first part, we showed that immunohistochemical methods (IHC) to detect α-syn in paraffin embedded gastrointestinal tissue were limited by some technical challenges, but when using full thickness colonic sample they allow to detect with high accuracy pathological α-syn. In the second part, using biochemical approach, we have shown that α-syn native enteric may not have the same tendency to assemble itself as in brain and its expression level was not changed in Parkinson's disease. Our results are promising for the development of enteric histological biomarkers of PD and suggest a different propensity between the enteric and brain α-syn to become pathological. Key

الإتاحة: http://www.theses.fr/2016NANT1010/documentTest

المؤلفون: de Cock, Valérie Cochen, Dodet, Pauline, Leu-Semenescu, Smaranda, Aerts, Cécile, Abril, Beatriz, Castelnovo, Giovanni, Landragin, Nicolas, Drapier, Sophie, Olivet, Hélène, Corbillé, Anne Gaelle, Leclair-Visonneau, Laurène, Anheim, Mathieu, Vidailhet, Marie, Arnulf, Isabelle, Doulazmi, Mohamed, Roze, Emmanuel

المساهمون: Clinique Beau Soleil Montpellier, EuroMov - Digital Health in Motion (Euromov DHM), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom Paris (IMT)-Institut Mines-Télécom Paris (IMT)-Université de Montpellier (UM), CHU Pitié-Salpêtrière AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Clinique du Millénaire - Oc Santé Montpellier, Oc Santé Montpellier, Centre d'Investigation Clinique Rennes (CIC), Université de Rennes (UR)-Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Ponchaillou -Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Ponchaillou, Polyclinique Saint Laurent Rennes, Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes), The Enteric Nervous System in gut and brain disorders U1235 (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre Hospitalier Universitaire Strasbourg (CHU Strasbourg), Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A-IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Orkyn Ltd Aguettant Pharma Société Française de Médecine Esthétique

المصدر: ISSN: 2330-1619 ; Movement Disorders Clinical Practice ; https://hal.science/hal-04148898Test ; Movement Disorders Clinical Practice, 2023, 10 (8), pp.1192-1197. ⟨10.1002/mdc3.13799⟩.

مصطلحات موضوعية: Parkinson's disease, motor fluctuations, treatment, sleep, insomnia, sleepiness, apomorphine, [SDV]Life Sciences [q-bio], [SCCO.NEUR]Cognitive science/Neuroscience

الوصف: International audience ; Background: We recently demonstrated in a randomized controlled trial (APOMORPHEE, NCT02940912) that night-time only subcutaneous apomorphine infusion improves sleep disturbances and insomnia in patients with advanced Parkinson's disease and moderate to severe insomnia. Objectives: To identify the best candidates for receiving night-time only subcutaneous apomorphine infusion in routine care. Methods: In this post-hoc analysis of APOMORPHEE, we compared the characteristics of patients according to whether they chose to continue night-time only subcutaneous apomorphine infusion at the end of the study period or not. Results: Half of the patients (22/42) chose to continue the treatment. Off duration (day or night), painful Off dystonia, and insomnia severity at baseline were associated with night-time only apomorphine continuation. Multivariate analysis retained only Off duration as an independent predictor of continuation. Conclusions:The best candidates for night-time only apomorphine are patients with severe and prolonged Off periods (day or night) and severe insomnia.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37635769; hal-04148898; https://hal.science/hal-04148898Test; https://hal.science/hal-04148898/documentTest; https://hal.science/hal-04148898/file/Cochen%20De%20Cock%20-%20Night%E2%80%90Time%20Apomorphine%20Infusion%20Who%20Are%20the%20Best%20Candidates.pdfTest; PUBMED: 37635769

الإتاحة: https://doi.org/10.1002/mdc3.13799Test
https://hal.science/hal-04148898Test
https://hal.science/hal-04148898/documentTest
https://hal.science/hal-04148898/file/Cochen%20De%20Cock%20-%20Night%E2%80%90Time%20Apomorphine%20Infusion%20Who%20Are%20the%20Best%20Candidates.pdfTest

المؤلفون: Cochen De Cock, Valérie, Dodet, Pauline, Leu‐Semenescu, Smaranda, Aerts, Cécile, Abril, Beatriz, Castelnovo, Giovanni, Landragin, Nicolas, Drapier, Sophie, Olivet, Hélène, Corbillé, Anne‐Gaëlle, Leclair‐Visonneau, Laurène, Anheim, Mathieu, Vidailhet, Marie, Arnulf, Isabelle, Doulazmi, Mohamed, Roze, Emmanuel

المصدر: Movement Disorders Clinical Practice ; volume 10, issue 8, page 1192-1197 ; ISSN 2330-1619 2330-1619

الوصف: Background We recently demonstrated in a randomized controlled trial (APOMORPHEE, NCT02940912) that night‐time only subcutaneous apomorphine infusion improves sleep disturbances and insomnia in patients with advanced Parkinson's disease and moderate to severe insomnia. Objectives To identify the best candidates for receiving night‐time only subcutaneous apomorphine infusion in routine care. Methods In this post‐hoc analysis of APOMORPHEE, we compared the characteristics of patients according to whether they chose to continue night‐time only subcutaneous apomorphine infusion at the end of the study period or not. Results Half of the patients (22/42) chose to continue the treatment. Off duration (day or night), painful Off dystonia, and insomnia severity at baseline were associated with night‐time only apomorphine continuation. Multivariate analysis retained only Off duration as an independent predictor of continuation. Conclusions The best candidates for night‐time only apomorphine are patients with severe and prolonged Off periods (day or night) and severe insomnia.

الإتاحة: https://doi.org/10.1002/mdc3.13799Test

المؤلفون: Rouaud, Tiphaine, Corbillé, Anne-Gaëlle, Damier, Philippe

المصدر: Revue du Rhumatisme ; volume 90, issue 1, page 86-92 ; ISSN 1169-8330

مصطلحات موضوعية: Rheumatology

الإتاحة: https://doi.org/10.1016/j.rhum.2022.11.009Test
https://api.elsevier.com/content/article/PII:S1169833022007657?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1169833022007657?httpAccept=text/plainTest

المؤلفون: Fabbri, Margherita, Rousseau, Vanessa, Corvol, Jean-Christophe, Sommet, Agnès, Tubach, Florence, De Rycke, Yann, Bertille, Nathalie, Selvarasa, Yajiththa, Carvalho, Stephanie, Chaigneau, Véronique, Brefel-Courbon, Christine, Ory-Magne, Fabienne, Tessier, Samuel, Tir, Melissa, Bereau, Matthieu, Meissner, Wassilios, Thiriez, Claire, Marques, Ana, Remy, Philippe, Schneider, Vincent, Moro, Elena, Defebvre, Luc, Houeto, Jean Luc, Prange, Stephane, Eusebio, Alexandre, Geny, Christian, Frismand, Solène, Damier, Philippe, Reuther, Caroline Giordana, Castelnovo, Giovanni, Benatru, Isabelle, de Maindreville, Anne Doe, Drapier, Sophie, Maltête, David, Lagha-Boukbiza, Ouhaid, Rascol, Olivier, Aubignat, Mickael, Magnin, Eloi, Burbaud, Pr Pierre, Guehl, Pr Dominique, Foubert-Samier, Alexandra, Laurens, Brice, Boraud, Thomas, Vergnet, Sylvain, Bendetowicz, David, Palpacuer, Thomas, Debilly, Bérengère, Derost, Philippe, Beal, Charlotte, Salhi, Hayet, Dormeuil, Alice, Petit, Aimée, Gravier, Alban, Dupont, Gwendoline, Garnier, Lucie, Fraix, Valérie, Castrioto, Anna, Meoni, Sara, Carriere, Nicolas, Danaila, Teodor, Laurencin, Chloé, Thobois, Stéphane, Azulay, Jean-Philippe, Fluchere, Frédérique, Charif, Mahmoud, Picot, Marie-Christine, Hopes, Lucie, Corbille, Anne-Gaelle, Rouaud, Tiphaine, Derkinderen, Pascal, Alecu, Cosmin, Heraud, Charlotte, de Verdal, Marie, Degos, Bertrand, Mangone, Graziella, Sambin, Sara, Lanore, Aymeric, Courtin, Thomas, Mariani, Louise-Laure, Khoury, Fouad, Menon, Poornima, Cormier-Dequaire, Florence, Flamand-Roze, Emmanuel, Grabli, David, Hainque, Elodie, Vidhaillet, Marie, Meneret, Aurélie, Delorme, Cécile, Foucard, Cendrine, von Raison, Florian, Elbaz, Alexis, Hartmann, Andreas, Leclercq, Vincent, Ansquer, Solène, Leh, Frederique, Leclercq, Marion, Costentin, Guillaume, Brefel Courbon, Christine, Leung, Clemence, Catala, Hélène, Causel, Astrid, Gaiffe, Emilie, Dupouy, Sandrine, Villars, Sandrine, Lai, Wei-Ho, Bari, Rachida, Chevanne, Damien, Durand, Elodie, Rieu, Isabelle, Bernard, Stephane, Garsault, Corinne, Boudjema, Noel, Grebent, Pascale, Kistner, Andrea, Pelissier, Pierre, Santraine, Valérie, Gaudin, Thomas, Boutet, Pierre, Caire, Catherine, Nouira, Manel, Verna, Claudia, Jardel, Amory, Puisieux, Salomé, Clement, Guillemette, Le Monnier, Lili, Frenais, Régis, Le Dily, Séverine, Chaigneau, Rachel, Ferrier, Vanessa, David, Elodie, Fra, Leslie, Foucaran, Elsa, Dongmo-Kenfack, Carole, Beauzor, Florence, Le, Mickael, Messar, Sonia, Liot, Sophie, Rabois, Emilie, Bonnaire-Verdier, Margaux, Kestens, Françoise, Gourhan, Rozenn, Lopez-Alfaro, Sandra, Houvenaghel, Jean-François, Alexandre, Mélanie, Bourdonnais, Christine, Vernon, Linda, Boumediene, Ahmed, Julie, Céline, Lobstein, Aurette, Longato, Nadine, Mitterle, Marie-Pierre, Philips, Clélie, Rummel, Hugo, Bras, Stéphanie, Harroch, Estelle, Gillet, Claudia

المساهمون: Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique CHU Toulouse, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d’Excellence en Maladies Neurodégénératives (NeuroToul), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Toulouse NeuroImaging Center (ToNIC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Plateforme F-CRIN, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique Neurosciences CHU Pitié Salpêtrière (CIC Neurosciences), Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département Neurologie CHU Toulouse, Pôle Neurosciences CHU Toulouse, Centre Régional de PharmacoVigilance CHU Toulouse (CRPV), Service Pharmacologie Clinique CHU Toulouse, Pôle Santé publique et médecine publique CHU Toulouse, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Santé publique et médecine publique CHU Toulouse, Service de neurologie Amiens, CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Service de Neurologie CHRU Besançon, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre de référence de l’atrophie multisystématisée CHU Toulouse, Institut des Maladies Neurodégénératives Bordeaux (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), University of Otago Dunedin, Nouvelle-Zélande, New Zealand Brain Research Institute (NZBRI), Service de Neurologie CHU Caen, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Neuro-Psycho Pharmacologie des Systèmes Dopaminergiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Unité Médicale des Troubles du Mouvement, Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-Clinique de Neurologie, European Academy of Neurology Vienna, Austria (Head Office), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), Epidémiologie des Maladies Chroniques en zone tropicale (EpiMaCT), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-OmégaHealth (ΩHealth), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service de neurologie C, centre expert parkinson, Hospices civils de Lyon, hôpital neurologique Pierre-Wertheimer, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de neurologie et pathologie du mouvement, Hôpital Roger Salengro Lille -Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), EuroMov - Digital Health in Motion (Euromov DHM), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom Paris (IMT)-Institut Mines-Télécom Paris (IMT)-Université de Montpellier (UM), Département de neurologie Montpellier, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier)-Hôpital Gui de Chauliac CHU Montpellier, Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier)-Université de Montpellier (UM), Centres Mémoire de Ressources et de Recherche CHRU Nancy (CMRR de Lorraine), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie CHU Nice, Hôpital Pasteur Nice (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Neurologie CHU Nimes (Pôle NIRR), Hôpital Universitaire Carémeau Nîmes (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CIC Poitiers – Centre d'investigation clinique de Poitiers (CIC 1402), Université de Poitiers = University of Poitiers (UP)-Centre hospitalier universitaire de Poitiers = Poitiers University Hospital (CHU de Poitiers La Milétrie )-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Maison Blanche, Hôpital universitaire Robert Debré Reims (CHU Reims), Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Ponchaillou, Centre d'Investigation Clinique Rennes (CIC), Université de Rennes (UR)-Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Ponchaillou -Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie Rouen, CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Neuroendocrine, Endocrine and Germinal Differentiation Communication (NorDic)

المصدر: ISSN: 0300-9564.

مصطلحات موضوعية: Parkinson's disease, Amantadine, NS-Park, Motor complications, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology

الوصف: International audience ; Objective: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD).Background: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres.Methods: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis).Results: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users.Conclusions: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs.

العلاقة: hal-04575054; https://hal.science/hal-04575054Test

الإتاحة: https://doi.org/10.1007/s00702-024-02772-4Test
https://hal.science/hal-04575054Test

المؤلفون: Espay, Alberto J, Stocchi, Fabrizio, Pahwa, Rajesh, Albanese, Alberto, Ellenbogen, Aaron, Ferreira, Joaquim J, Giladi, Nir, Gurevich, Tanya, Hassin-Baer, Sharon, Hernandez-Vara, Jorge, Isaacson, Stuart H, Kieburtz, Karl, LeWitt, Peter A, Lopez-Manzanares, Lydia, Olanow, C Warren, Poewe, Werner, Sarva, Harini, Yardeni, Tami, Adar, Liat, Salin, Laurence, Lopes, Nelson, Sasson, Nissim, Case, Ryan, Rascol, Olivier, Afshari, Mitra, Amelin, Alexander, Arkadir, David, Badarny, Samih, Balaguer Martinez, Ernest, Bogucki, Andrzej, Boyd, James, Buyan Dent, Laura, Carroll, Camille, Chaudhuri, Kallol Ray, Cooney, Jeffrey, Corbillé, Anne-Gaëlle, Danaila, Teodor, De Pandis, Maria Francesca, Dethy, Sophie, Dhall, Rohit, Djaldetti, Ruth, Durif, Franck, Flitman, Stephen, Freire Alvarez, Eric, Goudreau, John, Grandas Perez, Francisco, Isa, Arnaldo, Juncos, Jorge L, Kanchana, Sulada, Klodowska-Duda, Gabriela, Koziorowski, Dariusz, Kulisevsky Bojarski, Jaime, Lopez Lozano, Juan, Luo, Lan, Lytvynenko, Nataliya, Marconi, Roberto, Marques, Ana Raquel, Martinez Castrillo, Juan Carlos, Martinez Torres, Irene, Mentreddi, Aashoo, Mir Rivera, Pablo, Moskovko, Sergii, Neryanova, Yuliya, Onofrj, Marco, Ostrem, Jill, Pacchetti, Claudio, Pavese, Nicola, Pellicano, Clelia, Revuelta, Gonzalo, Rodrigues, Ana Margarida, Rodriguez, Ramon, Rudzinska, Monika, Sarwar, Nighat, Schwartzbard, Julie, Scorr, Laura, Slevin, John, Slobodin, Tatyana, Spalletta, Gianfranco, Tagliati, Michele, Tai, Yen, Tessitore, Alessandro, Valkovic, Peter, Verhagen, Leo, Vostrikova, Elena, Yahalom, Gilad, Zalyalova, Zuleykha, Zarubova, Katerina, Zhukova, Irina

الوصف: © 2024 Elsevier Ltd. All rights reserved. ; Background: Conventional oral levodopa therapy for the treatment of Parkinson's disease can be associated with variations in plasma concentrations. Levodopa infusion strategies might provide more consistent drug delivery and fewer motor fluctuations. We aimed to assess the safety and efficacy of a continuous 24 h/day subcutaneous infusion of ND0612 (a levodopa-carbidopa solution) compared with oral immediate-release levodopa-carbidopa for the treatment of motor fluctuations in people with Parkinson's disease. Methods: We conducted a phase 3, randomised, double-blind, double-dummy, active-controlled, multicentre trial at 117 academic and community neurology sites in 16 countries, including in Europe, Israel, and the USA. Eligible participants were men and women aged 30 years or older with a diagnosis of Parkinson's disease (Hoehn and Yahr stage ≤3 in the on state) who experienced at least 2·5 h/day of off time. Participants underwent an open-label run-in phase (<12 weeks), during which time optimal regimens were established for both oral immediate-release levodopa-carbidopa and for 24 h/day subcutaneous ND0612 infusion (levodopa-carbidopa 60·0/7·5 mg/mL), with supplemental oral levodopa-carbidopa if needed. Participants were then randomly assigned (1:1) to 12 weeks of double-blind treatment with their optimised regimen of either subcutaneous ND0612 or oral levodopa-carbidopa, with matching oral or subcutaneous placebo given as required to maintain blinding. Randomisation was done via an interactive web response system, stratified by region, using a permuted block schedule. Participants, study partners, treating investigators, study site personnel, and the sponsor were masked to treatment group allocation. The primary efficacy endpoint was the change from baseline (ie, time of randomisation, when all patients were receiving an optimised open-label ND0612 regimen) to end of the double-blind phase in total daily on time without troublesome dyskinesia, analysed by ...

العلاقة: https://www.sciencedirect.com/journal/the-lancet-neurologyTest; Lancet Neurol. 2024 May;23(5):465-476; http://hdl.handle.net/10451/64632Test

الإتاحة: https://doi.org/10.1016/S1474-4422Test(24)00052-8
http://hdl.handle.net/10451/64632Test

المؤلفون: Benkirane, Mehdi, da Cunha, Dylan, Marelli, Cecilia, Larrieu, Lise, Renaud, Mathilde, Varilh, Jessica, Pointaux, Morgane, Baux, David, Ardouin, Olivier, Vangoethem, Charles, Taulan, Magali, Daumas Duport, Benjamin, Bergougnoux, Anne, Corbillé, Anne Gaelle, Cossée, Mireille, Juntas Morales, Raul, Tuffery-Giraud, Sylvie, Koenig, Michel, Isidor, Bertrand, Vincent, Marie Claire

المساهمون: Physiologie & médecine expérimentale du Cœur et des Muscles U 1046 (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier), Mécanismes moléculaires dans les démences neurodégénératives (MMDN), École Pratique des Hautes Études (EPHE), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Universitaire de Recherche Clinique (IURC Montpellier), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)

المصدر: ISSN: 0006-8950.

مصطلحات موضوعية: [SDV]Life Sciences [q-bio]

الوصف: International audience ; Abstract Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an inherited late-onset neurological disease caused by bi-allelic AAGGG pentanucleotide expansions within intron 2 of RFC1. Despite extensive studies, the pathophysiological mechanism of these intronic expansions remains elusive. We screened by clinical exome sequencing two unrelated patients presenting with late onset ataxia. Repeat Primer-PCR was used for RFC1 AAGGG intronic expansion identification. RFC1 mRNA expression was assessed by quantitative reverse transcription PCR We identified the first two CANVAS affected patient who are compound heterozygous for a RFC1 truncating variants (p.Arg388* and c.575delA, respectively) and a pathological AAGGG expansion. RFC1 expression studies in whole blood showed a significant reduction of RFC1 mRNA for both patients compared to 3 patients with bi-allelic RFC1 expansions. In conclusion, this observation provides clues that suggest bi-allelic RFC1 conditional loss of function as the cause of the disease.

العلاقة: hal-03750598; https://hal.science/hal-03750598Test; https://hal.science/hal-03750598/documentTest; https://hal.science/hal-03750598/file/2022%20Benkirane%20et%20al.,%20RFC1%20nonsense.pdfTest

الإتاحة: https://doi.org/10.1093/brain/awac280Test
https://hal.science/hal-03750598Test
https://hal.science/hal-03750598/documentTest
https://hal.science/hal-03750598/file/2022%20Benkirane%20et%20al.,%20RFC1%20nonsense.pdfTest