Direct reprogramming for HD Disease Modelling

Project Information

DISMOD-HD

Grant agreement ID: 753077

DOI

10.3030/753077

Project closed

EC signature date 10 April 2017

Start date 15 May 2017

End date 12 October 2019

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 180 277,20

EU contribution

€ 180 277,20

Coordinated by

UNIVERSITA DEGLI STUDI DI MILANO
Italy

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

Reporting period: 2017-05-15 to 2019-05-14

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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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