Brain Involvement iN Dystrophinopathies

Resultado final

Behaviour: Dp140 restoration

Behavioural outcomes of Dp140 restoration in mdx52 using direct AON brain injection or AAVU7.

Behaviour: Dp71 restoration

Behavioural outcome of Dp71 restoration using AAV in Dp71-null and mdx3cv.

Mdx intellectual defects

Motor emotional and learning deficits shared or unique to the different mouse models

Differences between mouse models

Executive dysfunctions shared or unique to the different mouse models

Transcriptional changes in dystrophin absence

Characterization of transcriptional changes related to the loss of specific dystrophin isoforms.

First study approvals package

First study subject approvals package (prior to enrolment of first study subject). (i) Final version of study protocol as submitted to regulators/ethics committee(s), (ii) Registration number of clinical study in a WHO-or ICMJE- approved registry (with the possibility to post results), (iii) Approvals (ethics committees and national competent authority if applicable) required for invitation/enrolment of first subject in at least one clinical centre.

Communication, Dissemination and Exploitation plan (first release)

First release of the Communication, Dissemination and Exploitation Plan.

Neurobehavioural definition

Definition of the neurobehavioural co-morbidities of the 180 DMD and 90 BMD patients belonging to the 3 different genotype categories.

Genotype/phenotype correlations in mice

Genotype/ phenotype correlation in two mdx mouse models

First study subject approvals package

First study subject approvals package' (prior to enrolment of first study subject). (i) Final version of study protocol as submitted to regulators/ethics committee(s), (ii) Registration number of clinical study in a WHO-or ICMJE- approved registry (with the possibility to post results), (iii) Approvals (ethics committees and national competent authority if applicable) required for invitation/enrolment of first subject in at least one clinical centre.

Questionnaire definition

Definition of a questionnaire that will be distributed via UPPMD to national advocacy groups and registries

Mdx5cv validation

Validation of the mdx5cv mouse model

Report on a status of posting results

Report on status of posting results in the study registry(s) – For each clinical study, a report on the status of posting results in the study registry(s) must be submitted as a deliverable, including timelines if/when final posting of results is scheduled after end of funding period.We will post the result of the brain MRI studies, which will include the brain structure, perfusion and structural connectivity in DMD and BMD patients by month 53.

Dystrophin protein complex characterisation

Characterisation of dystrophin protein complexes in different brain regions from normal mouse brains

Mouse robust phenotypes

Duplication of robust phenotypes selected for WP4 in the different mouse models.

Behaviour: Dp427 restoration

Behavioural outcome of Dp427 restoration using direct AON brain injection or AAV-U7 in the mdx52.

Gene and proteomic knowledge map

Knowledge map of gene and proteomic changes associated with comorbidities in other than DMDBMD

Genotype/phenotype correlations in DMD/BMD brains

Genotype / phenotype correlations for brain structure, perfusion, functional connectivity in DMD and BMD patients

Post-natal brain restoration therapy

Effect of post-natal dystrophin restoration therapy.

Comorbidity ‘supercluster' formation

Formation of brain comorbidity supercluster and clinical trial advisory group on brain comorbidities

Mouse comorbidities

Comorbidities shared or unique to the different mouse models

Brain transcriptional changes

Characterization of transcriptional changes in different brain regions of mouse models lacking different dystrophin isoforms

Behaviour: Dp427 or Dp127+Dp140 restoration

Behavioural outcome of Dp427 or Dp127+Dp140 restoration in mdx52 using systemically administered new generations of AONs (tcDNA ).

WP5 - Midterm recruitment report

Midterm recruitment report Report for each clinical study to be scheduled for the point when 50 of the study population is expected to have been recruited

Report on status of posting results

Report on status of posting results in the study registry(s) – For each clinical study, a report on the status of posting results in the study registry(s) must be submitted as a deliverable, including timelines if/when final posting of results is scheduled after end of funding period. The end of the clinical deep phenotyping including the neurobehavioural and neurocognitive profile of the DMD and BMD patients will be delivered at month 47.

Neurocognitive profile definition

Definition of the neurocognitive profile of the 180 DMD patients and 90 BMD patients belonging to the 3 genotype categories.

Overlapping features related to co-morbidities

List of the overlapping features related to the co-morbidities identified in both DMD/BMD and in other disorders.

Omics datasets

Generation of proteomics and transcriptomics datasets to be used in WP7 to identify molecular networks related to cognition and emotional responses that are associated with dystrophin.

Dystrophin isoform localisation: mice

Characterisation of dystrophin isoform localisation in different brain regions from normal mouse brains.

Questionnaire on comorbidities to families

Questionnaire to families to ascertain severity of comorbidities

Prediction outcomes for different therapies

Outcome prediction for different dystrophin therapies

Dystrophin isoform localisation:humans

Characterisation of dystrophin isoform localisation in different brain regions from normal human brains

Protocol optimisation

Optimization of the neurocognitive and neurobehavioural protocols to be used in the study

Communication, Dissemination and Exploitation plan (second release)

Second release of the Communication, Dissemination and Exploitation Plan.

Factors responsible for behavioural changes

List of factors responsible for the behavioural observation in mouse and man.

WP6 - Midterm recruitment report

Midterm recruitment report Report for each clinical study to be scheduled for the point when 50 of the study population is expected to have been recruited

Communication, Dissemination and Exploitation plan (final release)

Final release of the Communication, Dissemination and Exploitation Plan.

Project Website

The project website will be formally delivered in month 4, carrying general information about BIND and the planned public deliverables; it will then be updated at regular intervals, to report on activities, events, major achievements and to provide access to public deliverables.

Publicaciones

Investigating the role of dystrophin isoform deficiency in motor function in Duchenne muscular dystrophy

Autores: Mary Chesshyre, Deborah Ridout, Yasumasa Hashimoto, Yoko Ookubo, Silvia Torelli, Kate Maresh, Valeria Ricotti, Lianne Abbott, Vandana Ayyar Gupta, Marion Main, Giulia Ferrari, Anna Kowala, Yung-Yao Lin, Francesco Saverio Tedesco, Mariacristina Scoto, Giovanni Baranello, Adnan Manzur, Yoshitsugu Aoki, Francesco Muntoni
Publicado en: Journal of Cachexia, Sarcopenia and Muscle, 2022, ISSN 2190-5991
Editor: Springer Verlag
DOI: 10.1002/jcsm.12914

Partial restoration of brain dystrophin by tricyclo-DNA antisense oligonucleotidesalleviates emotional deficits in mdx52 mice

Autores: A. Saoudi, S. Barberat, O. Le Coz, O. Vacca, M. Doisy Caquant, Tensorer, E. Sliwinski, L. Garcia, F. Muntoni, C. Vaillend and A. Goyenvalle
Publicado en: Molecular Therapy Nucelic Acids, 2023, ISSN 2162-2531
Editor: Nature Publishing Group
DOI: 10.1016/j.omtn.2023.03.009

Understanding anxiety experienced by young males with Duchenne muscular dystrophy: a qualitative focus group study

Autores: Rachel E. Trimmer, William P.L. Mandy, Francesco Muntoni, Kate E. Maresh
Publicado en: Neuromuscular Disorders, 2024, ISSN 0960-8966
Editor: Elsevier BV
DOI: 10.1016/j.nmd.2023.12.002

Abnormal Expression of Synaptic and Extrasynaptic GABAA Receptor Subunits in the Dystrophin-Deficient mdx Mouse

Autores: F. Zarrouki, S. Goutal, O. Vacca, L. Garcia, N. Tournier, A. Goyenvalle, and C. Vaillend
Publicado en: International Journal of Molecular Sciences, 2022, ISSN 1422-0067
Editor: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms232012617

The unconditioned fear response in vertebrates deficient in dystrophin

Autores: Saba Gharibi, Cyrille Vaillend, Angus Lindsay
Publicado en: Progress in Neurobiology, 2024, ISSN 0301-0082
Editor: Pergamon Press Ltd.
DOI: 10.1016/j.pneurobio.2024.102590

297P In-depth behavioral characterization of Duchenne muscular dystrophy mouse models lacking one, multiple or all dystrophin isoforms in the brain

Autores: M. Van Putten, M. Verhaeg, L. van der Pijl, D. van de Vijver, C. Tanganyika-de Winter, T. Stan, A. Aartsma-Rus
Publicado en: Neuromuscular Disorders, Edición 43, 2024, Página(s) 104441.492, ISSN 0960-8966
Editor: Elsevier BV
DOI: 10.1016/j.nmd.2024.07.501

Towards harmonization of clinical tools for assessing Brain Involvement in Dystrophinopathies (BIND); report of four expert workshops: Newcastle, Leiden, Rome, Paris

Autores: Jos Hendriksen, Pien Weerkamp, Ruben Miranda, Anna Kolesnik, Daniela Chieffo, David Skuse, Elizabeth Vroom, Chloe Geagan, Francesco Muntoni, Eugenio Mercuri
Publicado en: Neuromuscular Disorders, Edición 44, 2024, Página(s) 104452, ISSN 0960-8966
Editor: Elsevier BV
DOI: 10.1016/j.nmd.2024.104452

Duchenne muscular dystrophy patients lacking the dystrophin isoforms Dp140 and Dp71 and mouse models lacking Dp140 have a more severe motor phenotype

Autores: Francesco Muntoni and Mary Chessyre (UCL)
Publicado en: Journal of Cachexia, Sarcopenia and Muscle, 2022, ISSN 2190-6009
Editor: Wiley
DOI: 10.1002/jcsm.12914

Emotional behavioral and brain anatomy of the mdx52 mouse model of Duchenne muscular dystrophy

Autores: Cyrille Vaillend, A. Saoudi, F. Zarrouki, C. Sebrié, C. Izabelle, A. Goyenvalle, C. Vaillend
Publicado en: Disease Models and Mechanisms, 2021, ISSN 1754-8411
Editor: The company of Biologists
DOI: 10.1242/dmm.049028

AAV-Mediated Restoration of Dystrophin-Dp71 in the Brain of Dp71-Null Mice: Molecular, Cellular and Behavioral Outcomes

Autores: Ophélie Vacca, Faouzi Zarrouki, Charlotte Izabelle, Mehdi Belmaati Cherkaoui, Alvaro Rendon, Deniz Dalkara, Cyrille Vaillend
Publicado en: Cells, 2024, ISSN 2073-4409
Editor: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/cells13080718

Wechsler Scale Intelligence Testing in Males with Dystrophinopathies: A Review and Meta-Analysis

Autores: P. Weerkamp, E. Mol, D. Sweere, D. Schrans, R. J. Vermeulen, S. Klinkenberg, P. Hurks and J. Hendriksen
Publicado en: Brain Sciences, 2022, ISSN 2076-3425
Editor: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/brainsci12111544

Development of a novel startle response task in Duchenne muscular dystrophy

Autores: Kate Maresh,Andriani Papageorgiou, Deborah Ridout, Neil Harrison, William Mandy, David Skuse, Francesco Muntoni
Publicado en: Plos one, 2022, ISSN 1932-6203
Editor: Public Library of Science
DOI: 10.1371/journal.pone.0264091

Networking to Optimize Dmd exon 53 Skipping in the Brain of mdx52 Mouse Model

Autores: Mathilde Doisy, Ophélie Vacca, Claire Fergus, Talia Gileadi, Minou Verhaeg, Amel Saoudi, Thomas Tensorer, Luis Garcia, Vincent P Kelly, Federica Montanaro, Jennifer E Morgan, Maaike van Putten, Annemieke Aartsma-Rus , Cyrille Vaillend, Francesco Muntoni, Aurélie Goyenvalle
Publicado en: Biomedicines, 2024, ISSN 2227-9059
Editor: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/biomedicines11123243

Psychosocial adjustment in adults with Duchenne muscular dystrophy: A pilot study on a shortened parent-report questionnaire

Autores: P. Weerkamp, P. Collin, R. Maas, R. J. Vermeulen, S. Klinkenberg, J. Hendriksen
Publicado en: Neuromuscular Disorders, 2022, ISSN 1873-2364
Editor: Elsevier
DOI: 10.1016/j.nmd.2021.10.008

Psychological test usage in duchenne muscular dystrophy: An EU multi-centre study

Autores: Pien Weerkamp, Daniela Chieffo, Philippe Collin, Federica Moriconi, Andriani Papageorgiou, Isabella Vainieri, Ruben Miranda, Catherine Hankinson, Asmus Vogel, Sarah Poncet, Catherine Moss, Francesco Muntoni, Eugenio Mercuri, Jos Hendriksen
Publicado en: European Journal of Paediatric Neurology, 2023, ISSN 1090-3798
Editor: W. B. Saunders Co., Ltd.
DOI: 10.1016/j.ejpn.2023.06.007

A Longitudinal Follow-Up Study of Intellectual Function in Duchenne Muscular Dystrophy over Age: Is It Really Stable?

Autores: Daniela P R Chieffo, Federica Moriconi, Marika Pane, Simona Lucibello, Elisabetta Ferraroli, Giulia Norcia, Martina Ricci, Anna Capasso, Gianpaolo Cicala, Bianca Buchignani , Giorgia Coratti, Costanza Cutrona, Monia Pelizzari, Claudia Brogna, Jos G M Hendriksen, Francesco Muntoni, Eugenio Mercuri
Publicado en: Journal of Clinical Medicine, 2023, ISSN 2077-0383
Editor: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/jcm12020403

Investigating the Impact of Delivery Routes for Exon Skipping Therapies in the CNS of DMD Mouse Models

Autores: A. Saoudi, C. Fergu, T. Gileadi, F. Montanaro, JE Morgan, V. Kelly, T. Tensorer, L. Garcia, C. Vaillend, F. Muntoni and A. Goyenvalle
Publicado en: Cells, 2023, ISSN 2073-4409
Editor: MDPI
DOI: 10.3390/cells12060908

Social and emotional alterations in mice lacking the short dystrophin-gene product, Dp71

Autores: Rubén Miranda, Léa Ceschi, Delphine Le Verger, Flora Nagapin, Jean-Marc Edeline, Rémi Chaussenot, Cyrille Vaillend
Publicado en: Behavioral and Brain Functions, Edición 20, 2024, Página(s) https://behavioralandbrainfunctions.biomedcentral.com/articles/10.1186/s12993-024-00246-x, ISSN 1744-9081
Editor: BioMed Central
DOI: 10.1186/s12993-024-00246-x

Networking to Optimize Dmd exon 53 Skipping in the Brain of mdx52 Mouse Model

Autores: Mathilde Doisy, Ophélie Vacca, Claire Fergus, Talia Gileadi, Minou Verhaeg, Amel Saoudi, Thomas Tensorer, Luis Garcia, Vincent P Kelly, Federica Montanaro, Jennifer E Morgan, Maaike van Putten, Annemieke Aartsma-Rus , Cyrille Vaillend, Francesco Muntoni, Aurélie Goyenvalle
Publicado en: Biomedicines, 2023, ISSN 2227-9059
Editor: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/biomedicines11123243

Language Development in Preschool Duchenne Muscular Dystrophy Boys

Autores: Language Development in Preschool Duchenne Muscular Dystrophy Boys
Publicado en: Brain Sciences, 2022, ISSN 2076-3425
Editor: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/brainsci12091252

Partial Restoration of Brain Dystrophin and Behavioral Deficits by Exon Skipping in the Muscular Dystrophy X-Linked (mdx) Mouse

Autores: Faouzi Zarrouki Karima Relizani Flavien Bizot Thomas Tensorer Luis Garcia Cyrille Vaillend Aurélie Goyenvalle
Publicado en: Ann Neurol., 2022, ISSN 0364-5134
Editor: John Wiley & Sons Inc.
DOI: 10.1002/ana.26409

Brain Dp140 alters glutamatergic transmission and social behaviour in the mdx52 model of Duchenne muscular dystrophy

Autores: Hashimoto Y, Kuniishi H, Sakai K, Fukushima Y, Du X, Yamashiro K, Hori K, Motohashi N, Imamura M, Hoshino M, Yamada M, Araki T, Sakagami H, Takeda S, Itaka K, Ichinohe N, Muntoni F, Sekiguchi M, Aoki Y.
Publicado en: Prog Neurobiol., 2021, ISSN 0301-0082
Editor: Pergamon Press Ltd.
DOI: 10.1016/j.pneurobio.2022.102288

FAIRification and semantic modelling for Duchenneand Becker Muscular Dystrophy rare diseases

Autores: Pablo Perdomo-Quinteiro, Sergiu Sisminiuc, Paraskevi Sakellariou, Marco Roos, Pietro Spitali, Núria Queralt-Rosinach
Publicado en: SWAT4HCLS 2023: The 14th International Conference on Semantic Web Applications and Tools for Health Care and Life Sciences, 2023, ISSN 1613-0073
Editor: CEUR Workshop Proceedings

Startle responses in Duchenne muscular dystrophy: a novel biomarker of brain dystrophin deficiency

Autores: Kate Maresh, Andriani Papageorgiou, Deborah Ridout, Neil A Harrison, William Mandy, David Skuse, Francesco Muntoni
Publicado en: Research Article (peer reviewed), 2022, ISSN 1460-2156
Editor: Oxford University Press
DOI: 10.1093/brain/awac048

Automated analysis of behavioral assays in rodents with performance equivalent to manual scoring

Autores: Minou Verhaeg, Lizette van der Pijl, Luna Mastenbroek, Esmee van der Linde, Angel van Uffelen, Urani Leka, Tiberiu Stan, Maaike van Putten, Luciano Censoni
Publicado en: 2024
Editor: SWEBAGS

Resultado final

Publicaciones

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