Direct reprogramming for HD Disease Modelling

Informazioni relative al progetto

DISMOD-HD

ID dell’accordo di sovvenzione: 753077

DOI

10.3030/753077

Progetto chiuso

Data della firma CE 10 Aprile 2017

Data di avvio 15 Maggio 2017

Data di completamento 12 Ottobre 2019

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 180 277,20

Contributo UE

€ 180 277,20

Coordinato da

UNIVERSITA DEGLI STUDI DI MILANO
Italy

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

Periodo di rendicontazione: 2017-05-15 al 2019-05-14

Sintesi del contesto e degli obiettivi generali del progetto

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.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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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