Objectives

In Repair-HD, we propose to establish all the components necessary to take hPSCs-derived neuronal cells through to the point of 'first-in-man' clinical trial in HD, based on the highest principles of medicinal grade quality, demonstrated safety and ethical compliance.

The project's objective is to validate differentiation and preparation protocols of clinical grade stem cells suitable for use in clinical trials in Huntington's disease, along with the development of patient assessment protocols, ethical and regulatory frameworks and surgical delivery methods.

As most basic and clinically oriented research on hPSCs has to date focused on human embryonic stem cells (hESCs), we will start with GMP (Good Manufacturing Practice) grade hESCs in order to demonstrate and validate their responsiveness to MSN differentiation protocols. In parallel, we will generate GMP-compatible human induced pluripotent stem cells (hiPSCs) as an alternative donor cell source for deriving clinical grade hiPS-MSNs suitable for clinical use. The project will then compare the functional efficacy of hiPS-MSNs alongside the clinically ready hES-MSNs for selection of the optimal source to progress to clinical application by the end of the study. Selection of lead candidate hPS-MSNs for clinical trial will be made by assessing the reliability, safety, functional efficacy and capacity for clinical translation in vitro and in vivo.