Cell replacement therapies in Huntington’s disease (HD) aim to repair the nervous system by reintroducing the previously degenerated medium spiny neurons (MSNs) of the striatum and thereby restoring efferent and afferent projections. Despite significant advances in the generation of efficient protocols to differentiate pluripotent cells into authentic MSNs little is known about their functional efficacy. This study aimed to evaluate the survival, safety, integration, connectivity and functional efficacy of a hESC-derived cell therapy product (CTP) that was designed to be enriched for MSNs progenitors. Human CTP was stereotaxically transplanted into the striatum of a rat quinolinic acid model of HD. Rodents are treated with cyclosporine to prevent rejection and are being assessed on a range of behavioural tests sensitive to both motor and non-motor impairments over a period of 27 weeks to allow graft differentiation and development. While this is an on-going experiment, the following has been established with the current hESC-derived MSN CTP: (1) it consistently survives following transplantation into the rodent brain (as evidenced by bioluminescence imaging) and expresses markers of MSN differentiation (e.g., Darpp-32, CTIP2); (2) is safe (i.e., no evidence of neural overgrowth); (3) it is capable of forming functional synapses with the host brain and (4) and there is preliminary evidence of reduced motor bias in HD rats grafted with the hESC-derived CTP.