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Neural transplantation in Huntington disease: Long-term grafts in two patients

From the Departments of Pathology, Division of Neuropathology (C.D.K., J.A.S., T.J.M.), and Neurology (P.D.S.), University of Washington Medical Center; and Department of Neurology (J.B.L., T.D.B.), VA-Puget Sound Health Care System (Geriatric [T.D.B.], Mental Illness [J.B.L.], and Parkinson's Disease [J.B.L.] Research, Education, and Clinical Centers), Seattle, WA; and Neurosciences Institute (O.K.), St. John's Regional Medical Center, Oxnard, CA.

Address correspondence and reprint requests to Dr. Thomas Montine, Department of Pathology, University of Washington, Harborview Medical Center, Box 359791, Seattle, WA 98104 tmontine{at}u.washington.edu

Objective: Clinical trials of fetal neural tissue transplantation for Huntington disease (HD) have been conducted with variable clinical results. However, no long-term analysis of graft survival and integration has been published. Here, we report the pathologic findings in two patients with HD who died 74 and 79 months after transplantation.

Methods: Methods used were pathologic examination, histochemistry, and immunohistochemistry.

Results: Neostriatum from both patients showed typical neuropathologic changes of advanced HD. Surviving grafts were identified in both patients (6/6 sites and 7/8 sites, respectively) as well-demarcated nests within host neostriatum with associated needle tracts. Grafted neurons adopted either dominant calbindin/parvalbumin or calretinin immunoreactivity (IR). Few neurofilament, MAP-2, DARPP-32, tyrosine hydroxylase, or calbindin IR processes traversed the host parenchyma-graft interface despite minimal junctional gliosis. Immunohistochemistry for CD68 showed microgliosis that was more pronounced in host striatum than graft. Scattered CD45 and CD3 IR cells were present within grafts and host parenchyma. No ubiquitin IR neuronal intranuclear inclusions were identified in graft neurons, although these were prevalent in host cells.

Conclusions: These two autopsies confirm previous findings of neuronal differentiation and survival of transplanted fetal tissue from the ganglionic eminence and also demonstrate viability of neurons from fetal transplants in human neostriatum for more than 6 years. Despite prolonged survival, these grafts had poor integration with host striatum that is likely responsible for lack of clear clinical improvement in these patients.

Editorial, see page 2055

Supported by ADRC NIA P50-AG005136-22, Veterans Affairs research funds, the University of Washington HDSA Center of Excellence, and the Nancy and Buster Alvord endowment.

Disclosure: The authors report no conflicts of interest.

Received October 12, 2006. Accepted in final form March 1, 2007.

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				B. D. Ross, S. A. Frank, and K. Biglan LONG-TERM FETAL CELL TRANSPLANT IN HUNTINGTON DISEASE: STAYIN' ALIVE Neurology, March 4, 2008; 70(10): 815 - 816. [Full Text] [PDF]

				S. Frank and K. Biglan Long-term fetal cell transplant in Huntington disease: Stayin' alive Neurology, June 12, 2007; 68(24): 2055 - 2056. [Full Text] [PDF]