Direct reprogramming for HD Disease Modelling

Información del proyecto

DISMOD-HD

Identificador del acuerdo de subvención: 753077

DOI

10.3030/753077

Proyecto cerrado

Fecha de la firma de la CE 10 Abril 2017

Fecha de inicio 15 Mayo 2017

Fecha de finalización 12 Octubre 2019

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 180 277,20

Aportación de la UE

€ 180 277,20

Coordinado por

UNIVERSITA DEGLI STUDI DI MILANO
Italy

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

Período documentado: 2017-05-15 hasta 2019-05-14

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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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