Potential of Choroid Plexus Epithelial Cell Grafts for Neuroprotection in Huntington’s Disease: What Remains Before Considering Clinical Trials

Abstract

The choroid plexuses (CPs) help maintain the extracellular milieu of the brain by modulating chemical exchange between the cerebrospinal fluid and brain parenchyma, surveying the chemical and immunological status of the brain, detoxifying the brain, secreting a nutritive "cocktail" of polypeptides, and participating in repair processes following trauma. Based on recent pre-clinical studies in animal models, a novel therapeutic approach has been suggested that involves transplanting CP for treating acute and chronic brain diseases. To date most studies have focused on rodent and primate models of Huntington's disease (HD) with demonstrations that transplants of CP can prevent the behavioral and anatomical consequences of striatal degeneration. Despite the encouraging results that lend support to the possibility of protecting vulnerable neurons in HD, critical basic science issues remain unexamined that limit the translation of the pre-clinical findings into clinical evaluations of CP transplants for HD. Here we briefly outline the logic behind using this novel cell source for transplantation, the pre-clinical data supporting this concept, and most importantly identify several critical, gating issues that remain prior to moving this approach forward in a meaningful clinical manner.