Development of human striatal anlagen after transplantation in a patient with Huntington's disease

Gallina, Pasquale; Paganini, Marco; Lombardini, Letizia; Saccardi, Riccardo; Marini, Mirca; Cristofaro, Maria Teresa De; Pinzani, Pamela; Salvianti, Francesca; Crescioli, Clara; Rita, Andrea Di; Bucciantini, Sandra; Mechi, Claudia; Sarchielli, Erica; Moretti, Marco; Piacentini, Silvia; Gritti, G; Bosi, Alberto; Sorbi, Sandro; Orlandini, Giovanni; Vannelli, Gabriella Barbara; Lorenzo, Nicola Di

doi:10.1016/j.expneurol.2008.06.003

Cited by 40 publications

(38 citation statements)

References 24 publications

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“…The series consisted of 26 HD patients (tables 1 and 2) who were acquainted with the transplantation programme and adhered to the protocol. Ten patients asked to undergo transplantation and were grafted between 2006 and 2008—patients 1, 4, 6, 8 having been partially described 13 14. All patients were evaluated with the Unified HD Rating Scale (UHDRS)20—high functional and cognitive scores denote better performance, low behavioural and motor scores denote better performance.…”

Section: Methodsmentioning

confidence: 99%

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

Paganini

Biggeri

Romoli

et al. 2013

Journal of Neurology, Neurosurgery & Psychiatry

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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.

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Section: Methodsmentioning

confidence: 99%

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

Paganini

Biggeri

Romoli

et al. 2013

Journal of Neurology, Neurosurgery & Psychiatry

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“…Bilateral, robotic-assisted (NeuroMate Robotic System, Schaerer Mayfield, France) transplantation of human striatal primordium took place in two sessions (45 days apart, left side first) in 2009. Neurotransplantation protocols have been previously described [11,12]. For each procedure, both ganglionic eminences were dissected from the floor of the forebrain ventricles of a single legally aborted fetus (10.5 and 9.3 weeks old for left and right grafting, respectively).…”

Section: Clinical Presentationmentioning

confidence: 99%

Human Striatum Remodelling after Neurotransplantation in Huntington's Disease

Gallina

Paganini

Biggeri³

et al. 2014

Stereotact Funct Neurosurg

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Background: Restoration of functions in Huntington's disease (HD) by neurotransplantation stems from the formation of a striatum-like structure capable of establishing host connections as a result of grafted striatal neuroblast maturation. For the first time, we demonstrated some developmental steps accomplished by progenitor cells in the brain of an HD patient and analysed the molecular asset of the human primordium. Case Report: Surgery involved bilateral (two sessions) stereotactic, caudate-putaminal transplantation of whole ganglionic eminence fragments from single legally aborted fetuses. MRI showed that the tissue deposits of the left hemisphere grew and joined to constitute a single tissue mass that remodelled basal ganglia anatomy and remained stable in size over time. No evidence of graft growth was observed contralaterally. PET demonstrated increased striatal and stable cortical metabolism. Unified Huntington's Disease Rating Scale assessments demonstrated improvement of motor performances, which faded over the 36-month follow-up. Cognitive performance tended to decrease at a lower rate than before transplantation. Conclusion: The striatal primordium grew into the host brain and this process was associated with metabolic change and some clinical benefit. The study suggests the plasticity and reparative potential of un-manipulated primordium in an era where promising cell-based therapies are still in their infancy.

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“…The clinical evolution of 4 patients was satisfactory, probably due to the presence of immunosuppression. Donor-recipient histocompatibility might explain the growth response differences observed between grafts in one of the anti-HLA-positive patients [38,39]. Indeed, alloimmunization without signs of rejection has been reported in four grafted patients out of 13 studied during the course of a clinical trial involving fetal neural transplantation in patients with Huntington's disease, whereas an ongoing rejection process was observed in a fifth transplanted patient.…”

Section: Striatal Neuroblasts Transplantationmentioning

confidence: 99%