Context

There are compelling reasons for considering regenerative medicine in a wide range of neurodegenerative conditions such as Alzheimer's, Parkinson's or Huntington's disease. Together, these conditions represent a very large and growing disease burden and the vast majority is currently untreatable. Furthermore, for most of these conditions targeted pharmacological treatments are a long way off as the detailed pathogenesis is not yet described.

The last decade has seen major advances in exploring cell replacement therapy for a variety of neurodegenerative diseases. This therapeutic option consisting of replacing diseased cells with healthy ones is interesting in conditions where major cell loss is relatively focal in area or involves a specific neural cell type.

Huntington's disease (HD) provides an excellent test-bed for cell replacement therapy. The disease is anatomically well focused as the brunt of the disease in the early stages is largely borne by Medium Spiny Neurons (MSNs) in the striatum. Additionally, the range of good animal models of HD greatly facilitates translation between animal and clinical studies. Finally, the availability of a highly reliable genetic test allows confident diagnosis of the condition in life, which increases the power and reliability of clinical studies.

In order to replace striatal MSNs lost in HD disease with new cells that are able to take over their function and reconnect the circuitry, it is essential to identify a reliable renewable source of cells for neural transplantation. Human pluripotent stem cells (hPSCs) present an attractive potential source as they can be expanded indefinitely in vitro, can be stored by cryopreservation and can be differentiated into mature somatic cells.