Background Cultured skin fibroblasts from HD patients seem to be an attractive model for in vitro studies of molecular pathology in HD, and in the hunt for HD biomarkers, as sampling is minimally invasive and the effect of the mutation can be studied in the correct genetic background.

Aims Here we discuss results gathered from the literature together with some of our own unpublished results on HD patient fibroblasts.

Outcome Although HD primary fibroblast cultures have been established and studied for a long time, results revealing characteristic phenotypic traits of this cell type are sparse. Many investigations have focused on growth characteristics but no conclusion could be drawn just as studies of cellular morphology so far have yielded somewhat confounding results. There have been multiple explanations suggested, including variations in growth characteristics of individual cell lines, which are also known from normal fibroblast cultures, and differences in culture conditions like the use of different culture media, concentration of serum, addition of antibiotics, surface of culture disc, etc, conditions which make it difficult to compare results obtained from different experimental set-ups. Recently, examples of functional deficits have been found in HD fibroblasts including vesicular trafficking, lipid metabolism and proteasome inhibition as well as growth factor and enzyme activity changes. Future investigations are needed to reveal the pathways involved and to show if they relate to changes in CNS.

Conclusion Our considerations are useful for planning collection of skin biopsies and multicentre studies on cultured fibroblasts.