Enhancement of the response to levodopa therapy after intrastriatal transplantation of autologous sympathetic neurons in patients with Parkinson disease

Abstract

Sympathetic neuron autografts were found to improve performance status in patients with PD by reducing the time spent in the off phase. This clearly indicates that sympathetic ganglion tissue, the use of which involves few ethical issues, can be an efficacious donor source in cell transplantation therapy for PD. Further studies are needed to determine whether the grafts may provide long-lasting clinical benefits.

The search for a curative cell therapy in Parkinson's disease

“…The mode of action for sympathetic neuronal transplants is thought to be through their capacity to convert and store dopamine in the extracellular space, as human sympathetic neurons express both AADC and VMAT2 in culture [30] and following transplantation into a rat PD model [31]. Again as the practicability and reproducibility of this approach remains in doubt, its adoption in the clinic is greatly limited.…”

“…In these studies ganglion tissue has been excised from the sympathetic trunk either at the thoracic [30,31] or cervical [32][33][34] level and then transplanted into the striatum of patients. This autologous transplantation of sympathetic ganglion neurons has been associated with a reduction in the "off" time and an increase in the "on" time in approximately half of the PD patients receiving such transplants [34].…”

Shifting the balance: cell-based therapeutics as modifiers of the amyotrophic lateral sclerosis–specific neuronal microenvironment

“…In 4 patients who underwent follow-up, no overt evidence of graft-related adverse events was reported; however, no tissue analysis could be performed to confirm cell survival. 83 Authors of a similar allogeneic study utilized retinal pigment epithelial cells from a cadaveric source for injection into the postcommissural putamen of 6 patients with advanced PD. Immunosuppression was not used, and the authors failed to note clinical events associated with graft injection or magnetic resonance imaging signal intensity alterations indicative of a graft rejection as late as the 2-year follow-up.…”

High Titer Retroviral Gene Transduction to Neural Progenitor Cells for Establishment of Donor Cells for Neural Transplantation to Parkinsonian Model Rats

“…Cell transplantation therapy has been performed for patients with Parkinson's disease using dopaminergic tissues of ventral mesencephalon of human fetuses, sympathetic ganglia, or pig fetuses for the last 20 years. 4,12,14,16) The transplants have shown long-term survival in the host striata and provided therapeutic value in several hundred patients. 12,14,16) However, an adequate supply of fetal tissues is difficult to obtain because one parkinsonian patient needs at least four to five fetuses.…”

“…4,12,14,16) The transplants have shown long-term survival in the host striata and provided therapeutic value in several hundred patients. 12,14,16) However, an adequate supply of fetal tissues is difficult to obtain because one parkinsonian patient needs at least four to five fetuses. 12,16) Therefore, richer sources of cells/tissues have been investigated, in particular neural stem cells or neural progenitor cells (NPCs) characterized by self-renewal and multipotency.…”