Outcome of cell suspension allografts in a patient with Huntington’s disease

For patients with incurable neurodegenerative disorders such as Huntington’s (HD) and Parkinson’s disease, cell transplantation has been explored as a potential treatment option. Here, we present the first clinicopathological study of a patient with HD in receipt of cell-suspension striatal allografts who took part in the NEST-UK multicenter clinical transplantation trial. Using various immunohistochemical techniques, we found a discrepancy in the survival of grafted projection neurons with respect to grafted interneurons as well as major ongoing inflammatory and immune responses to the grafted tissue with evidence of mutant huntingtin aggregates within the transplant area. Our results indicate that grafts can survive more than a decade posttransplantation, but show compromised survival with inflammation and mutant protein being observed within the transplant site

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

Outcome Following Intrastriatal Fetal Mesencephalic Grafts for Parkinson\u27s Patients is Directly Related to the Volume of Grafted Tissue

The effect of varying the volume of grafted fetal mesencephalic tissue was studied in patients with idiopathic Parkinson\u27s disease in a single- blinded study. Evaluations were performed according to the Core Assessment Program for Intracerebral Transplantation and videotaped both prior to transplantation and in 3-month intervals after transplantation. One group, low-volume grafts (six subjects; mean age, 57.2 years), received ventral mesencephalon grafts from one to two donors with an approximate volume up to 20 mm3, while the second group, high-volume grafts (seven subjects; mean age, 59.5 years), received ventral mesencephalon grafts from three or more donors with an approximate volume of 24 mm3. Both groups of patients demonstrated significant improvement over presurgical baseline scores on all major parameters. The high-volume group had significantly greater improvements on all the UPDRS scores and also better performance on a variety of motor performance tasks over that seen among low-volume patients. These results indicate that variations of fetal graft volume do have an impact on clinical outcome