Long-Term Safety, Immunologic Response, and Imaging Outcomes following Neural Stem Cell Transplantation for Pelizaeus-Merzbacher Disease

Summary: Four boys with Pelizaeus-Merzbacher disease, an X-linked leukodystrophy, underwent transplantation with human allogeneic central nervous system stem cells (HuCNS-SC). Subsequently, all subjects were followed for an additional 4 years in this separate follow-up study to evaluate safety, neurologic function, magnetic resonance imaging (MRI) data, and immunologic response. The neurosurgical procedure, immunosuppression, and HuCNS-SC transplantation were well tolerated and all four subjects were alive at the conclusion of the study period. At year 2, all subjects exhibited diffusion MRI changes at the implantation sites as well as in more distant brain regions. There were persistent, increased signal changes in the three patients who were studied up to year 5. Two of four subjects developed donor-specific HLA alloantibodies, demonstrating that neural stem cells can elicit an immune response when injected into the CNS, and suggesting the importance of monitoring immunologic parameters and identifying markers of engraftment in future studies. : Gupta and colleagues show that transplantation with allogeneic central nervous system stem cells can be performed safely in humans with minimal morbidity. Immunologic data, however, show that neural stem cells can elicit an immune response following transplantation, suggesting the importance of monitoring immunologic parameters. Keywords: Pelizaeus-Merzbacher disease, neural stem cells, leukodystrophy, myelin, oligodendrocyte, transplantation, pediatric, neurodegenerative disease