Porcine xenografts in parkinson's disease and Huntington's disease patients: Preliminary results

The observation that fetal neurons are able to survive and function when tr ansplanted into the adult brain fostered the development of cellular therap y as a promising approach to achieve neuronal replacement for treatment of diseases of the adult central nervous system. This approach has been demons trated to be efficacious in patients with Parkinson's disease after transpl antation of human fetal neurons. The use of human fetal tissue is limited b y ethical, infectious, regulatory, and practical concerns. Other mammalian fetal neural tissue could serve as an alternative cell source. Pigs are a r easonable source of fetal neuronal tissue because of their brain size, larg e litters, and the extensive experience in rearing them in captivity under controlled conditions. In Phase I studies porcine fetal neural cells grafte d unilaterally into Parkinson's disease (PD) and Huntington's disease (HD) patients are bring evaluated for safety and efficacy. Clinical improvement of 19% has been observed in the Unified Parkinson's Disease Rating Scale "o ff" state scores in 10 PD patients assessed 12 months after unilateral stri atal 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 a fter transplantation. Twelve HD patients have shown a favorable safety prof ile and no change in total functional capacity score 1 year after unilatera l striatal placement of up to 24 million fetal porcine striatal cells. Xeno transplantation of fetal porcine neurons is a promising approach to deliver y 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 outcom e of diseases that are slowly progressive.