The purpose of this paper was to offer a review of the rationale, methods, biological and clinica... more The purpose of this paper was to offer a review of the rationale, methods, biological and clinical results of human fetal striatal transplantation (HFST) in the treatment of Huntington's disease (HD). HD is a heritable neurodegenerative disease in which degeneration of neurons in the striatum leads to motor, psychiatric and cognitive deficits. The disease is progressive and inexorably lethal. At present there are no curative treatments for HD. A restorative therapy based on the intrastriatal transplantation of striatal neuroblasts taken from human fetus is currently being explored as potential treatment in selected HD patients. Pilot clinical trials of HFST have been started in few neurosurgery restorative centres. Results demonstrated that HFST is feasible and safe without relevant adverse effects; grafted neuroblasts survive, grow without evidence of neoplasia or teratoma, build new tissue with striatal-like imaging features, and move into the host brain towards short and long...
Fetal grafting in a human diseased brain was thought to be less immunogenic than other solid orga... more Fetal grafting in a human diseased brain was thought to be less immunogenic than other solid organ transplants, hence of minor impact on the efficacy of the transplant. How much prophylactic immune protection is required for neural allotransplantation is also debated. High-sensitive anti-HLA antibody screening in this field has never been reported. Sixteen patients with Huntington's disease underwent human fetal striatal transplantation in the frame of an open-label observational trial which is being carried out at Florence University. All patients had both brain hemisphere grafted in two separate robotic-stereotactic procedures. The trial started in February 2006 with the first graft to the first patient (R1). R16 was given his second graft on March 2011. All patients received triple immunosuppressive treatment. Pre- and post-transplant sera were analyzed for the presence of anti-HLA antibodies using the multiplexed microsphere-based suspension array Luminex xMAP technology. Median follow-up was 38.5 months (range 13-85). Six patients developed anti-HLA antibodies, which turned out to be donor-specific. Alloimmunization occurred in a time window of 0-49 months after the first neurosurgical procedure. The immunogenic determinants were both cross-reactive group, structurally defined public epitopes and private specificities of mismatched HLA antigens. One patient had non donor-specific anti-HLA antibodies in her pre-transplant serum sample, possibly due to previous sensitization events. Although the clinical significance of donor-specific antibodies is far from being established, particularly in the setting of neuronal transplantation, these findings underline the need of careful pre- and post-transplant immunogenetic evaluation of patients with intracerebral grafts.
The purpose of this paper was to offer a review of the rationale, methods, biological and clinica... more The purpose of this paper was to offer a review of the rationale, methods, biological and clinical results of human fetal striatal transplantation (HFST) in the treatment of Huntington's disease (HD). HD is a heritable neurodegenerative disease in which degeneration of neurons in the striatum leads to motor, psychiatric and cognitive deficits. The disease is progressive and inexorably lethal. At present there are no curative treatments for HD. A restorative therapy based on the intrastriatal transplantation of striatal neuroblasts taken from human fetus is currently being explored as potential treatment in selected HD patients. Pilot clinical trials of HFST have been started in few neurosurgery restorative centres. Results demonstrated that HFST is feasible and safe without relevant adverse effects; grafted neuroblasts survive, grow without evidence of neoplasia or teratoma, build new tissue with striatal-like imaging features, and move into the host brain towards short and long...
Fetal grafting in a human diseased brain was thought to be less immunogenic than other solid orga... more Fetal grafting in a human diseased brain was thought to be less immunogenic than other solid organ transplants, hence of minor impact on the efficacy of the transplant. How much prophylactic immune protection is required for neural allotransplantation is also debated. High-sensitive anti-HLA antibody screening in this field has never been reported. Sixteen patients with Huntington's disease underwent human fetal striatal transplantation in the frame of an open-label observational trial which is being carried out at Florence University. All patients had both brain hemisphere grafted in two separate robotic-stereotactic procedures. The trial started in February 2006 with the first graft to the first patient (R1). R16 was given his second graft on March 2011. All patients received triple immunosuppressive treatment. Pre- and post-transplant sera were analyzed for the presence of anti-HLA antibodies using the multiplexed microsphere-based suspension array Luminex xMAP technology. Median follow-up was 38.5 months (range 13-85). Six patients developed anti-HLA antibodies, which turned out to be donor-specific. Alloimmunization occurred in a time window of 0-49 months after the first neurosurgical procedure. The immunogenic determinants were both cross-reactive group, structurally defined public epitopes and private specificities of mismatched HLA antigens. One patient had non donor-specific anti-HLA antibodies in her pre-transplant serum sample, possibly due to previous sensitization events. Although the clinical significance of donor-specific antibodies is far from being established, particularly in the setting of neuronal transplantation, these findings underline the need of careful pre- and post-transplant immunogenetic evaluation of patients with intracerebral grafts.
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Papers by E. Ghelli