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Targeting ASTROcytes with cutting-edge EDITING technologies to treat the Alexander disease

Project description

A gene-editing treatment for Alexander disease

Alexander disease (AxD), an autosomal dominant neurodegenerative disorder, is caused by missense mutations in the gene encoding the glial fibrillary acidic protein (GFAP), a key intermediate filament protein of astrocytes. This leads to the formation of GFAP aggregates and the activation of the stress response, compromising central nervous system homeostasis. The EU-funded ASTRO-EDITING project aims to recover astrocyte function by correcting GFAP mutational hotspots. For this purpose, scientists will follow a gene-editing approach based on adeno-associated virus vectors. The project will provide proof-of-concept of in vivo editing in astrocytes as a potential gene therapy strategy for AxD, offering at the same time a novel therapeutic approach for the treatment of other neurodegenerative disorders.


Alexander disease (AxD) is an autosomal dominant neurodegenerative disorder caused by missense mutations in the gene encoding the glial fibrillary acidic protein (GFAP), the major intermediate filament protein in astrocytes. Accumulation of GFAP aggregates in Rosenthal fibres leads to impairment of proteasomal activity and hyperactivation of the stress response, thus compromising astrocyte functions and altering the homeostasis of the central nervous system (CNS). Currently, this orphan disease lacks a cure.
The proposed project aims at providing in vivo proof-of-concept of safety, efficiency and efficacy of a novel and definitive AAV gene therapy approach based on gene editing / base editing strategies targeting GFAP mutational hotspots to recover pathological phenotypes in astrocytes. The candidate expects to outline novel editing platforms for widespread in vivo targeting of CNS astrocytes that could be applied for the treatment of AxD, as proposed in ASTRO-EDITING, and prospectively for disease modelling studies and therapeutic treatments of other neurological and psychiatric disorders by targeting pathological pathways involved in primary astrocyte degeneration or dysfunctional/maladaptive astrogliosis.
The proposal addresses the European issue of Horizon 2020, in the social challenge “Health, Demographic Change and Wellbeing” endeavours for the call “Better health and care, economic growth and sustainable health disease”, subject SC1-BMC-04-2018 “Rare Disease European Joint Programme Cofund”.
The expertise of the host laboratory, the international environment of OSR and the personalized career development plan will significantly reinforce candidate's competences and knowledge in the gene therapy field, expand his portfolio of therapeutic areas, create a new research niche, and strengthen his organizational, management and interpersonal skills, thus favouring the progressive acquisition of independence as experienced researcher in the scientific community.


Net EU contribution
€ 183 473,28
20132 Milano

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Nord-Ovest Lombardia Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Total cost
€ 183 473,28