Safety of Intrastriatal Neurotransplantation for Huntington\u27s Disease Patients

Fetal neural transplantation has been shown to be a feasible, safe, and according to a number of recent reports, effective treatment for Parkinson\u27s disease (PD). Fetal striatal transplantation may be as feasible, safe, and effective a treatment for Huntington\u27s disease (HD), a disorder for which there is currently no effective treatment. This report describes our experience with fetal striatal transplantation to adult striatum in three HD patients. Three moderately advanced, nondemented HD patients received transplantation of fetal striatal tissue. The striatal precursor was selectively obtained from the lateral ganglionic eminence. Each patient received bilateral grafts from five to eight donors, placed into the caudate nucleus (one graft on each side) and the putamen (four grafts on each side). All three patients had HD as documented by family history DNA heterozygosity (17-20 and 48-51 repeats), magnetic resonance imaging (MRI) revealing striatal atrophy, and 2-deoxyglucose positron emission tomography revealing striatal hypometabolism. All patients had been evaluated using the Unified Huntington\u27s Disease Rating Scale and appropriate neuropsychological tests for at least 3 months prior to transplantation. One year following transplantation, MRI of all three patients revealed that the grafts survived and grew within the striatum without displacing surrounding tissue. No patients demonstrated adverse effects of the surgery or the associated cyclosporin immunosuppression, nor did any patient exhibit deterioration following the procedure. The limited experience provided by these three patients indicates that fetal tissue transplantation can be performed in HD patients without unexpected complications

Translation of Cell Therapies to the Clinic: Characteristics of Cell Suspensions in Large-Diameter Injection Cannulae

With the use of cell replacement therapies as a realistic prospect for conditions such as Parkinson's and Huntington's diseases, the logistics of the delivery of cell suspensions to deep brain targets is a topic for consideration. Because of the large cannulae required for such procedures, we need to consider the behaviour of cell suspensions within the cannulae if we are to ensure that the injected cells are distributed as intended within the target tissue. We have investigated the behaviour of primary embryonic cell suspensions of neural tissue, in cannulae of different diameters, using a protocol designed to mimic the handling and injection of cells during clinical application. Internal cannula diameter had a large effect on the distribution of cells during their dispensation from the syringe. In vertical, or near vertical cannulae, cells settled towards the tip of the needle, and were dispensed unevenly, with the majority of cells emerging in the first 10-20% of the injectate. In horizontal or near-horizontal cannulae we observed the opposite effect, such that few cells were dispensed in the first 80% of the injectate, and the majority emerged in the final 10-20%. Use of a glass cannula showed that the results obtained using the horizontal cannula were caused by settling and adherence of the cells on the side of the cannulae, such that during dispensation, the overlying, cell-free solution was dispensed first, prior to the emergence of the cells. We show that the behaviour of cells in such cannulae is affected by the cannula diameter, and by the material of the cannula itself, and in horizontal cannulae, uneven expulsion of cells from the needle can be ameliorated by regular rotation of the cannula during the procedure. We discuss the potential impact of these observations on the translation of cell therapies to the clinic