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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 €

EC-Contrib. €

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.

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

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 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.	IT (GENOVA)	coordinator	2˙000˙000.00

Map

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

List of publications.
year	authors and title	journal	last update
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 ManagÃ², Carola A Haas, Maria Summa, Rosalia Bertorelli, Francesco Papaleo, Michael K SchÃ¤fer, 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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