Nigral grafts in animal models of Parkinson's disease. Is recovery beyond motor function possible?

Abstract

Parkinson's disease (PD) has long been considered predominantly to be a "movement disorder," and it is only relatively recently that nonmotor symptoms of PD have been recognized to be a major concern to patients. Consequently, there has been surprisingly little investigation into the feasibility of utilizing cell replacement therapies to ameliorate any of the nonmotor dysfunctions of PD. In this chapter, we identify nonmotor impairments associated predominately with dopaminergic dysmodulation, evaluate the few emerging studies that have identified a role for dopamine and nigral transplantation in nonmotor performance, and consider a number of outstanding questions and considerations dominating the field of nigral transplantation today. Preliminary results obtained from rodent models of PD, despite being limited in number, give clear indications of graft effects on striatal processing beyond the simple activation of motor output and promise a major, exciting, and fruitful new avenue of research for the next decade. We can now consider the prospect of rewriting the opportunities for treating patients, with new stem cell sources to be complemented by new targets for therapeutic benefit.