Porcine Xenografts in Parkinson's Disease and Huntington's Disease Patients: Preliminary Results

Abstract

The observation that fetal neurons are able to survive and function when transplanted into the adult brain fostered the development of cellular therapy as a promising approach to achieve neuronal replacement for treatment of diseases of the adult central nervous system. This approach has been demonstrated to be efficacious in patients with Parkinson's disease after transplantation of human fetal neurons. The use of human fetal tissue is limited by ethical, infectious, regulatory, and practical concerns. Other mammalian fetal neural tissue could serve as an alternative cell source. Pigs are a reasonable source of fetal neuronal tissue because of their brain size, large litters, and the extensive experience in rearing them in captivity under controlled conditions. In Phase I studies porcine fetal neural cells grafted unilaterally into Parkinson's disease (PD) and Huntington's disease (HD) patients are being evaluated for safety and efficacy. Clinical improvement of 19% has been observed in the Unified Parkinson's Disease Rating Scale "off" state scores in 10 PD patients assessed 12 months after unilateral striatal transplantation of 12 million fetal porcine ventral mesencephalic (VM) cells. Several patients have improved more than 30%. In a single autopsied PD patient some porcine fetal VM cells were observed to survive 7 months after transplantation. Twelve HD patients have shown a favorable safety profile and no change in total functional capacity score 1 year after unilateral striatal placement of up to 24 million fetal porcine striatal cells. Xenotransplantation of fetal porcine neurons is a promising approach to delivery of healthy neurons to the CNS. The major challenges to the successful use of xenogeneic fetal neuronal cells in neurodegenerative diseases appear to be minimizing immune-mediated rejection, management of the risk of xenotic (cross-species) infections, and the accurate assessment of clinical outcome of diseases that are slowly progressive.

The contribution of farm animals to human health

“…Porcine islet cells have been transplanted to diabetic patients and were shown to be at least partially functional over a limited period of time [51]. Porcine fetal neural cells were transplanted into the brain of patients suffering from Parkinson's and Huntington's disease [52,53]. In a single autopsied patient the graft survived for .7 months and the transplanted cells formed dopaminergic neurons and glial cells.…”

T Cell-Activated Macrophages Are Capable of Both Recognition and Rejection of Pancreatic Islet Xenografts

“…Already there have been trials of pig neural cells for Parkinson's disease (1,2) and pig islet cells for type I diabetes (3,4). However, rejection remains the major impediment to their use.…”

Positron emission tomography imaging of transplant function

“…A pilot open study studying the safety and efficacy of porcine mesencephalic xenografts when transplanted unilaterally into striatum in 12 PD patients with severe disease has also been reported. 56 In this series, only 2 of 10 evaluable patients showed significant improvements in locomotor disability, rated with the UPDRS, but no increases in striatal 18 F-dopa uptake were evident.…”