Direct reprogramming for HD Disease Modelling

Informations projet

DISMOD-HD

N° de convention de subvention: 753077

DOI

10.3030/753077

Projet clôturé

Date de signature de la CE 10 Avril 2017

Date de début 15 Mai 2017

Date de fin 12 Octobre 2019

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 180 277,20

Contribution de l’UE

€ 180 277,20

Coordonné par

UNIVERSITA DEGLI STUDI DI MILANO
Italy

Periodic Reporting for period 1 - DISMOD-HD (Direct reprogramming for HD Disease Modelling)

Période du rapport: 2017-05-15 au 2019-05-14

Résumé du contexte et des objectifs généraux du projet

The objective of this project was to generate a new system to model Huntington’s Disease in human neurons, in vitro. To do so we have planned to use human primary fibroblasts donated by healthy donors or Huntington’s Disease (HD) patients and reprogram them into medium spiny neurons (MSNs), which are the neuronal population most affected by Huntington’s Disease.
The aim of the generation of this new model system is to allow us to study the characteristics of human neurons, both healthy and with HD, and thus to find and understand new pathological mechanisms that are leading to neuronal death in patients.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

During this project we have achieved the generation of MSNs in vitro, via direct reprogramming of human primary fibroblasts. However, we reached the end of the grant period before we could generate MSNs from fibroblasts of HD patients. This delay in the achievement of the proposed goals was due to unforeseen technical difficulties in the protocol for efficient reprogramming of human fibroblasts into MSNs.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

In conclusion, it was possible to reach the one of the proposed milestones, which saw the definition of a reprogramming cocktail for the direct conversion of human primary fibroblasts into MSNs in vitro, in the absence of antibiotic selection or pro-survival factors. This work constitutes an important stepping stone for further optimisation of highly efficient reprogramming strategies, aimed at studying human neurodegenerative disorders in vitro.

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