review © The American Society of Gene & Cell Therapy BACKGROUND: IMPETUS AND OUTCOMES WITH

Parkinson’s disease (PD) is a chronic, progressive neurodegenera-tive disease most widely recognized for the profound degeneration of mid-brain dopamine nigrostriatal neurons linked to serious motor symptoms.1 However, PD is far more complex than com-monly appreciated, with multiple etiologic variables and pathogenic pathways, complex pathologies, and a wide range of central nervous system (CNS) and non-CNS symptoms (Table 1).2,3 Moreover, wide gaps in our understanding still exist at each disease level (i.e., etiol-ogy, pathogenesis, pathology, symptoms), and the cause-effect rela-tionships between them remain especially obscure. Arguably, the most well-characterized relationship exists with regard to nigros-triatal degeneration linked to the key motor symptoms; currrent oral dopaminergic pharmaceuticals are effective in controlling these symptoms at early disease stages. However, the drugs ’ effec-tiveness decline with progressive pathology, leading to gradua