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GenEdiDS SIGNED

Rescuing Cognitive Deficits in Neurodevelopmental Disorders by Gene Editing in Brain Development: the Case of Down Syndrome

Total Cost €

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EC-Contrib. €

0

Partnership

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 GenEdiDS project word cloud

Explore the words cloud of the GenEdiDS project. It provides you a very rough idea of what is the project "GenEdiDS" about.

postnatally    preclinical    involvement    neuronal    etiologies    technological    abnormalities    syndrome    lasting    later    caused    life    animal    rescue    cas9    originate    actions    intervention    minimize    treatments    cornerstone    triplicated    disability    ds    share    brain    prenatally    chromosome    drug    avoiding    21    effect    gene    germline    neurodevelopmental    shown    crispr    chronic    viral    genetically    pharmacological    indicating    cognitive    translational    converging    models    editing    downstream    nevertheless    limited    intellectual    possibly    disorders    defective    mice    cells    stages    act    progenitors    extra    free    light    mostly    embryonic    networks    psychiatric    developmental    therapy    deficits    utero    of    manipulations    impairment    performed    noxious    parallel    ethical    nd    sequelae    options    manipulation    genetic    adults    safer    treatment    diagnosed    positive    educational    view    recover    genes   

Project "GenEdiDS" data sheet

The following table provides information about the project.

Coordinator
FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA 

Organization address
address: VIA MOREGO 30
city: GENOVA
postcode: 16163
website: www.iit.it

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Italy [IT]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-10-01   to  2022-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA IT (GENOVA) coordinator 2˙000˙000.00

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 Project objective

Neurodevelopmental disorders (ND) are chronic psychiatric conditions with different etiologies, but most share a strong genetic component, defective brain development, and cognitive impairment. Currently, treatment options are very limited, and early educational intervention is the cornerstone for the management of cognitive impairment in most ND, indicating the positive effect of early actions during brain development. Among ND, Down syndrome (DS) is caused by the presence of an extra chromosome 21, and it represents the leading cause of genetically-defined intellectual disability. Different pharmacological treatments targeting one of the many pathways downstream of the triplicated genes have been shown to rescue cognitive impairment in DS animal models. Nevertheless, most of these preclinical studies have been performed postnatally and often in adults, possibly because of concerns of unwanted drug side effects that may have long-lasting noxious sequelae on a developing brain at embryonic stages. On the other hand, viral (but also non-viral) gene therapy approaches in animal models of ND have been mostly neglected because of technical and ethical issues, when considered in the light of future translational applications. Yet, DS is mostly diagnosed prenatally, when many of its brain developmental abnormalities originate. Here, we will investigate whether in utero manipulation of specific and possibly converging gene networks in neuronal progenitors of DS mice by CRISPR-Cas9 gene-editing technology, may recover brain development and cognitive deficits later in life. Specifically targeting neuronal progenitors will allow us to act at early stages of brain development, while avoiding the involvement of genetic editing of germline cells and all related ethical issues. In parallel, we will also develop safer (viral-free) technological approaches for genetic manipulations in utero to minimize technical issues in the view of potential future translational applications.

 Publications

year authors and title journal last update
List of publications.
2018 Andrzej W. Cwetsch, Bruno Pinto, Annalisa Savardi, Laura Cancedda
In vivo methods for acute modulation of gene expression in the central nervous system
published pages: 69-85, ISSN: 0301-0082, DOI: 10.1016/j.pneurobio.2018.04.008
Progress in Neurobiology 168 2019-06-06
2019 Shovan Naskar, Roberto Narducci, Edoardo Balzani, Andrzej W. Cwetsch, Valter Tucci, Laura Cancedda
The development of synaptic transmission is time-locked to early social behaviors in rats
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-09156-3
Nature Communications 10/1 2019-06-06
2018 Joanna Szczurkowska, Francesca Pischedda, Bruno Pinto, Francesca Managò, Carola A Haas, Maria Summa, Rosalia Bertorelli, Francesco Papaleo, Michael K Schäfer, Giovanni Piccoli, Laura Cancedda
NEGR1 and FGFR2 cooperatively regulate cortical development and core behaviours related to autism disorders in mice
published pages: , ISSN: 0006-8950, DOI: 10.1093/brain/awy190
Brain 2019-06-06

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