Do foetal transplant studies continue to be justified in Huntington's disease?

Early CNS transplantation studies used foetal derived cell products to provide a foundation of evidence for functional recovery in preclinical studies and early clinical trials. However, it was soon recognised that the practical limitations of foetal tissue make it unsuitable for widespread clinical use. Considerable effort has since been directed towards producing target cell phenotypes from pluripotent stem cells (PSCs) instead, and there now exist several publications detailing the differentiation and characterisation of PSC-derived products relevant for transplantation in Huntington's disease (HD). In light of this progress, we ask if foetal tissue transplantation continues to be justified in HD research. We argue that (i) the extent to which accurately differentiated target cells can presently be produced from PSCs is still unclear, currently making them undesirable for studying wider CNS transplantation issues; (ii) foetal derived cells remain a valuable tool in preclinical research for advancing our understanding of which products produce functional striatal grafts and as a reference to further improve PSC-derived products; and (iii) until PSC-derived products are ready for human trials, it is important to continue using foetal cells to gather clinical evidence that transplantation is a viable option in HD and to use this opportunity to optimise practical parameters (such as trial design, clinical practices, and delivery strategies) to pave the way for future PSC-derived products.