24-07-08(16:35:52)
Authors:
Freeman TB 1; Cicchetti F 4; Saporta S 2; Hauser R 3; Olanow CW 5; Saint-Pierre M 4; Chu Y 6; Kordower JH 6
Institutions:
Department of Neurosurgery 1, Department of Anatomy 2, Department of Anatomy 3 University of South Florida; Centre de rescherche due CHUL 4; Mt. Sinai Medical Center 5; Rush University Medical Center 6
Title of abstract : The long-term survival of neural transplants in Parkinson’s disease and Huntington’s disease is attenuated via different mechanisms
Abstract text:
Two patients in our open-label Parkinson’s disease (PD) neural transplant trial died 14 years after transplantation. Grafted neurons demonstrated robust cell survival with tyrosine hydroxylase-ir. However, dopaminergic grafts were found to have Lewy body-like inclusions that stained positively for alpha synuclein, ubiquitin and thioflavin-s. Transplants also demonstrated minimal staining with dopamine transporter (DAT). These findings are in clear contrast to transplants in patients that died in 18 months after surgery, where markers of PD were not observed in the grafts and DAT-ir was evaluated.
In comparison, the brains of two patients who underwent fetal striatal transplantation for the treatment of Huntington’s disease (HD) over ten years earlier were evaluated histologically. Surviving grafts were identified bilaterally in both subjects using markers typical of striatal projection neurons and intraneurons. However, the transplants demonstrated more robust pathological changes than observed in either the host brains or similar transplants from a previous subject who came to autopsy 18 months after transplantation. Markers of HD were not expressed in the grafts.
The pathologic processes observed in our PD patients suggest that PD is an ongoing process that can affect grafted cells in a manner similar to what occurs in patients. Disease expression in the grafts was independent of immunologic and genetic mismatches between grafts and hosts. In comparison, graft survival was attenuated in patients with HD, more likely due to a poor trophic milieu for graft survival. Immunological factors may also influence long-term graft survival in both PD and HD patients.
