Commentary: Evaluation of Models of Parkinson's Disease

This publication is a review on the preclinical model used today for Parkinson's disease that take in consideration both preclinical model based on neurotoxin or mutations associated to familial Parkinson's disease (PD). The aim of this commentary is to introduce a new point of view about the actual preclinical models, open discussion, and propose a new preclinical model. The use of correct preclinical model to study the mechanisms and to test possible new therapies is essential to obtain successful results and new therapies. The discovery that dopamine loss was associated to the disease was essential to the use of L-dopa in Parkinson's disease therapy. L-dopa has been the most used drug in the disease treatment during near five decades despite the severe side effects observed after 4–6 years treatment (Segura-Aguilar et al., 2015). The actual treatment of the disease is based on dopaminergic and anti-cholinergics compounds. The scientific community and pharmaceutical companies have failed to find new drugs to halt the progression of the disease and the worst is that the focus to find new therapies is centered on drugs to alleviate the side effects of L-dopa such as dyskinesia. There are a long list of successful preclinical studies that have failed to translate these positive results to clinical studies and new therapies, for example pioglitazone, topiramate, GDNF, The question is why successful results in preclinical studies cannot be translated to clinical studies? In our opinion (i) The preclinical models based on exogenous neurotoxins such as 6-hydroxidopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been very useful and valuable tools to study mechanisms. However, these preclinical models do not reflect what happen in the disease and therefore, these models are worthless to develop new drugs. One of the features of these exogenous neurotoxins is that all induce a rapid and extensive degeneration in animals. In humans MPTP induced a severe Parkinsonism in just 3 days after the use of a synthetic illicit drugs contaminated with MPTP. The rapid and extensive degeneration induced by exogenous drugs contrast with the very slow degeneration in Parkinson where the take years to develop motor symptoms. How we can translate results from preclinical to clinical studies when the mode of action is complete different. The exogenous drugs are killing all possible dopaminergic neurons which have affinity, suggesting that the very slow degeneration observed in Parkinson's disease must be dependent on an endogenous neurotoxin. It has been reported a …