Cell Replacement Therapy for Parkinson's Disease

How Close Are We to the Clinic?

Javier Ganz; Nirit Lev; Eldad Melamed; Daniel Offen


Expert Rev Neurother. 2011;11(9):1325-1339. 

In This Article

Expert Commentary

Cell replacement therapy for PD was proposed three decades ago as a possible approach to treat PD. During this time, many milestones have been successfully reached, creating a lot of hope and excitement. It is now established that cells can be transplanted into the brain, integrate and survive for years, and release dopamine. Clinical studies demonstrated the feasibility of cell transplantation in human PD patients, demonstrating a proof of concept that CRT for PD can be possible.

Although positive results were obtained, several obstacles have kept this therapeutic approach away from the clinic. DA neuron production for replacement must be refined in order to produce 'pure' DA neurons and eliminate the danger of tumor production, as well as synaptic dysregulation and side effects. It is also crucial to elucidate where and how to graft these cells in order to amend the diseased DA system in PD. Most studies transplanted the cells in the striatum, which is not the natural place for DA neurons. The natural place for DA grafts would be the substatia nigra pars compacta, but implantation at this site raises severe surgical and physiological problems, including the feasibility of artificial reconstruction of the nigrostriatal pathway.

It is difficult to foresee complete motor improvement using the current CRT protocols, mainly because of the inability to fully restore the natural nigrostriatal pathway and the hostile environment in which the cells are transplanted. Nevertheless, protocol refinements in parallel with implantation improvements and environment-modifying therapies are expected to yield better results and enable the clinical utilization of CRT in PD.