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

Abstract

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.

Symptomatic Treatment of Huntington Disease

“…114 Similar pathologic findings were reported after the autopsy of the caudate and putamen of two HD patients who died at 74 and 79 months after the fetal tissue transplantation, confirming the survival of the grafts in the human striatum for more than 6 years, without evidence of graft rejection and without accumulation of ubiquitin-staining inclusions. 115 However, the graft integration in the host striatum was poor, possibly explaining the modest clinical improvement in these patients. There are no autopsy reports available from patients receiving transplanted porcine fetal striatal cell transplants 116 that would allow pathology comparisons between allografts and xenografts.…”

Cell therapy in Huntington disease

“…Although full recovery has not been observed following fetal allografts in the striatum of humans with HD, some suggestions of delayed disease progression indicate positive functional outcomes. 12,13 The contribution of these grafts to functional recovery is enhanced by the fact that implanted cells, lacking the disease-causing gene, do not themselves appear vulnerable to neurodegenerative processes, 56,83 an effect that is also seen in transplants in patients with PD. 86,87,126 All clinical trials to date have been focused on the transplantation of fetal-derived cells into the diseased striatum.…”

“…72,83 Fetal lateral ganglionic eminence was bilaterally grafted into striata with HD. Autopsy results revealed that grafts were clearly demarcated 83 and grew to 5-10% of the normal human caudate putamen tissue volume after 18 months in 1 patient.…”

“…72,83 Fetal lateral ganglionic eminence was bilaterally grafted into striata with HD. Autopsy results revealed that grafts were clearly demarcated 83 and grew to 5-10% of the normal human caudate putamen tissue volume after 18 months in 1 patient. 72 Grafted cells displayed morphological features characteristic of both the developing and the mature striatum 72,83 and were innervated by appropriate host target regions, 72 although the presence of efferents was very limited in the tissue from patients surviving Ͼ 6 years after transplantation, despite minimal gliosis within the grafted tissue.…”

“…72 Grafted cells displayed morphological features characteristic of both the developing and the mature striatum 72,83 and were innervated by appropriate host target regions, 72 although the presence of efferents was very limited in the tissue from patients surviving Ͼ 6 years after transplantation, despite minimal gliosis within the grafted tissue. 83 Notably, grafted fetal striatal cells survive, develop, and integrate into host tissue without being affected by the disease process itself; that is, no mutant huntingtin aggregates were observed within the transplanted region, and the graft showed no signs of immunological rejection. 56 The sparing of grafted tissue from disease progression has also been reported in other transplant cases, including in patients with PD.…”