CHAPTER 5 - Animal Models of Parkinson's Disease to Aid Drug Discovery and Development

Abstract

Parkinson's Disease (PD) is the second most common, age-related progressive neurodegenerative disorder. Two events have impacted significantly the discovery and development approaches for novel therapeutics for PD: (a) the discovery of disease-causing mutations in multiple genes and (b) an emerging appreciation that the pathophysiology and associated symptoms of PD are more widespread than those resulting from the progressive loss of the nigrostriatal dopamine projections. Specifically, there has been an emergence of new animal models based on genetic etiology of familial PD and hence a renewed focus on using the new animal models to develop therapeutic strategies aimed at slowing the progression of the disease as well as treating non-motor symptoms of PD. This chapter provides an overview of the current state of the PD research with a special emphasis on animal models that can help therapeutic discovery and development. It focuses on the animal models of disease pathophysiology and resultant symptoms. It presents a summary on the clinical syndrome and current therapies of PD to set the context for the discussion to follow on commonly used animal models, their phenotypes and how they correlate/reproduce disease pathophysiology or specific symptoms of PD. It also addresses the specific utility of animal models in drug discovery and development, paying attention to current challenges or gaps that hinder discovery and development of drugs addressing the unmet medical needs of PD patients. Additionally, the chapter offers some suggestions on the utility of classical animal models as well as emerging models to address these gaps and facilitate development of therapeutic interventions.