Cell Implantation Therapy

Experimental cell-based surgical therapies involve directly depositing cells capable of producing dopamine or other diffusible therapeutic molecule such as growth factors into the brain. Sources for implantable cells have included fetal tissue and cultured stem cells from embryonic sources, cells from the adrenal medulla and retinal pigment epithelium (RPE).  Recent advances in the development of induced pluripotent stem cells, which are produced by genetic treatment of adult cells from skin or other tissues, may provide cells suitable for therapeutic transplantation, as well as for in vitro drug screening.

Initial attempts to bypass the immunological issues of cell transplantation utilized adrenal medulla cell implants (grafts). However, clinical trials have demonstrated no systematic or lasting benefit from adrenal medulla grafts. Previous clinical trials for dopamine cell replacement used fetal tissue transplants. While open-label studies showed suggestions of efficacy, double-blind studies were inconclusive. Additionally, some patients who received fetal transplants experienced graft-induced dyskinesia (Freed et al., 2001; Mendez et al., 2002; Olanow et al., 2003; Vitek et al., 2003; Wenning et al., 1997). Many issues remain to be addressed in order to develop fetal transplants as a viable therapy for PD.

Another approach for using transplants for dopamine replacement involved the use of retinal pigment epithelial (RPE) cells as a source of dopamine (Watts et al., 2003). A Phase II double-blind trial reported that Spheramine (cultured human RPE cells on microcarriers) did not show efficacy in a blinded trial.

The composition, formulation, and delivery of the transplants, methods for induced differentiation of dopaminergic and other cell types, and the role of post-operative immunoreactivity need to be better understood and optimized, and are the subjects of ongoing pre-clinical and clinical research.