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A patient with Huntington’s disease and long-surviving fetal neural transplants that developed mass lesions

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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.

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Acknowledgments

The authors wish to thank Randi Small, Regina Bowman, Susan Rozell, Christiane Ullness, Lynne Greenup, Aimee Schantz, Chiyen Miller, and Mike Hobbs for expert technical support. We would also like to thank Dr. Michael Laflamme for helpful discussions. This research was supported by National Institutes of Health grants P50-AG005136 and 5T32-AG000238, Veterans Affairs research funds, the University of Washington Huntington’s Disease Society of America Center of Excellence, and the Nancy and Buster Alvord Endowment.

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Authors and Affiliations

  1. Division of Neuropathology, Department of Pathology, Harborview Medical Center, University of Washington Medical Center, Box 359791, Seattle, WA, 98104, USA

    C. Dirk Keene, Rubens C. Chang, Robert F. Hevner, Donald E. Born & Thomas J. Montine

  2. Department of Neurology, VA-Puget Sound Health Care System, University of Washington Medical Center, Seattle, WA, 98104, USA

    James B. Leverenz & Thomas D. Bird

  3. Department of Neurosurgery, University of Washington Medical Center, Seattle Children’s Hospital and Regional Medical Center, Seattle, WA, 98104, USA

    Robert F. Hevner

  4. Neurosciences Institute, St. John’s Regional Medical Center, Oxnard, CA, 93030, USA

    Oleg Kopyov

  5. Department of Neurology, UCLA, Los Angeles, CA, 90095, USA

    Susan Perlman

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  1. C. Dirk Keene
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  2. Rubens C. Chang
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  3. James B. Leverenz
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  4. Oleg Kopyov
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Correspondence to C. Dirk Keene.

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Keene, C.D., Chang, R.C., Leverenz, J.B. et al. A patient with Huntington’s disease and long-surviving fetal neural transplants that developed mass lesions. Acta Neuropathol 117, 329–338 (2009). https://doi.org/10.1007/s00401-008-0465-0

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  • DOI: https://doi.org/10.1007/s00401-008-0465-0

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