title: A patient with Huntington's disease and long-surviving fetal neural transplants that developed mass lesions.
abstract: Transplantation of human fetal neural tissue into adult neostriatum is an experimental therapy for Huntington's disease (HD). Here we describe a patient with HD who received ten intrastriatal human fetal neural transplants and, at one site, an autologous sural nerve co-graft. Although initially clinically stable, she developed worsening asymmetric upper motor neuron symptoms in addition to progression of HD, and ultimately died 121 months post transplantation. Eight neural transplants, up to 2.9 cm, and three ependymal cysts, up to 2.0 cm, were identified. The autologous sural nerve co-graft was found adjacent to the largest mass lesion, which, along with the ependymal cyst, exhibited pronounced mass effect on the internal capsules bilaterally. Grafts were composed of neurons and glia embedded in disorganized neuropil; robust Y chromosome labeling was present in a subset of grafts and cysts. The graft-host border was discrete, and there was no evidence of graft rejection or HD pathologic changes within donor neurons. This report, for the first time, highlights the potential for graft overgrowth in a patient receiving fetal neural transplantation.
authors.affiliation: Department of Pathology, Harborview Medical Center, University of Washington Medical Center, Seattle, 98104, USA. cdkeene@u.washington.edu
authors.forename: C Dirk
authors.initials: CD
authors.lastname: Keene
authors.forename: Rubens C
authors.initials: RC
authors.lastname: Chang
authors.forename: James B
authors.initials: JB
authors.lastname: Leverenz
authors.forename: Oleg
authors.initials: O
authors.lastname: Kopyov
authors.forename: Susan
authors.initials: S
authors.lastname: Perlman
authors.forename: Robert F
authors.initials: RF
authors.lastname: Hevner
authors.forename: Donald E
authors.initials: DE
authors.lastname: Born
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Bird
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000737:chemistry; D016380:Brain Tissue Transplantation / Q000276:immunology / Q000379:methods / Q000473:pathology*; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation*; D017809:Fatal Outcome; D005260:Female; D016332:Fetal Tissue Transplantation / Q000276:immunology / Q000379:methods / Q000473:pathology*; D006085:Graft Survival; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D013234:Stem Cells; D017211:Treatment Failure
chemical_list: D015415:Biomarkers