Fetal striatal grafting slows motor and cognitive decline of Huntington's disease

Abstract

ObjectiveTo assess the clinical effect of caudate-putaminal transplantation of fetal striatal tissue in Huntington's disease (HD).MethodsWe carried out a follow-up study on 10 HD transplanted patients and 16 HD not-transplanted patients. All patients were evaluated with the Unified HD Rating Scale (UHDRS) whose change in motor, cognitive, behavioural and functional capacity total scores were considered as outcome measures. Grafted patients also received morphological and molecular neuroimaging.ResultsPatients were followed-up from disease onset for a total of 309.3 person-years (minimum 5.3, median 11.2 years, maximum 21.6 years). UHDRS scores have been available since 2004 (median time of 5.7 years since onset, minimum zero, maximum 17.2 years). Median post-transplantation follow-up was 4.3 years, minimum 2.8, maximum 5.1 years. Adjusted post-transplantation motor score deterioration rate was reduced compared to the pretransplantation period, and to that of not-transplanted patients by 0.9 unit/years (95% CI 0.2 to 1.6). Cognitive score deterioration was reduced of 2.7 unit/years (95% CI 0.1 to 5.3). For grafted patients the 2-year post-transplantation [18F]fluorodeoxyglucose positron emission tomography (PET) showed striatal/cortical metabolic increase compared to the presurgical evaluation; 4-year post-transplantation PET values were slightly decreased, but remained higher than preoperatively. [123I]iodobenzamide single photon emission CT demonstrated an increase in striatal D2-receptor density during postgrafting follow-up.ConclusionsGrafted patients experienced a milder clinical course with less pronounced motor/cognitive decline and associated brain metabolism improvement. Life-time follow-up may ultimately clarify whether transplantation permanently modifies the natural course of the disease, allowing longer sojourn time at less severe clinical stage, and improvement of overall survival.

Human Striatum Remodelling after Neurotransplantation in Huntington's Disease

“…This result supports the hypothesis of a functional effect of the striatal graft. We observed a clinical benefit in our case, as seen in a few other long-term followed patients where neuroblast maturation was paralleled with clinical improvement [24,26,27]. On the other hand, no benefit has been detected in the absence of adequate graft development [28].…”

Fetal grafting for Huntington's disease. Is there a hope?

“…The recently published article by Paganini et al 1 report the clinical outcomes of 10 patients with Huntington's disease (HD) receiving fetal grafting in the striatum, and compared with 16 non-grafted HD controls. The authors assessed the transplantation effect through a model of change in slope (disease progression over time) following grafting, a reduced deterioration in motor scores of −2.0 units/year was observed compared with the pretransplantation period and non-transplanted patients, with chorea and ocular movements achieving the highest benefit 1.…”

“…The authors assessed the transplantation effect through a model of change in slope (disease progression over time) following grafting, a reduced deterioration in motor scores of −2.0 units/year was observed compared with the pretransplantation period and non-transplanted patients, with chorea and ocular movements achieving the highest benefit 1. Importantly, the slope of cognitive deterioration was also reduced.…”

“…To overcome these problems, Paganini et al 1 compared the slope of progression between the pretransplantation and post-transplantation periods as well as between transplanted and non-transplanted patients showing a positive effect. Importantly, their findings were supported by demonstrations of graft viability by increased striatal metabolism assessed by 18 F-fluorodeoxyglucose positron emission tomography in 10 patients at 2 years, which was maintained up to 4 years, and a mean increase in D2-receptor binding was documented by by single photon emission computed tomography (SPECT) in 3 patients at 12 months and in 1 patient at 24 months after transplantation;1 the latter is considered a more specific marker for graft functionality, particularly when assessed with 11 C-raclopride positron emission tomography 2…”

“…It is still unclear what should be the follow-up protocol after transplantation and what is the appropriate regimen and length of immunosuppression, as a mild inflammatory response against the graft has been documented 3. Patients with HD seem to have an increased risk of subdural haematomas after transplantation, probably secondary to underlying brain atrophy 1 3. It has been suggested that the observed improvement following transplantation results from reconstruction of damaged cortico-subcortical loops4 with no evidence that the graft can slow the degeneration process of surrounding host cells.…”