Refinement of the MPTP model for Parkinson’s disease in the marmoset

Abstract

The increasing prevalence of age-related neurodegenerative diseases is a growing concern for the ageing societies. Parkinson’s disease is a major progressive motor disorder of the brain caused by specific degeneration of the dopamine-producing neurons in the substantia nigra, which govern the control of muscle movement. Despite intensive research efforts, no cure has been found, and we still have to rely on symptom control treatment. The paucity of valid preclinical models that faithfully reproduce clinical and pathogenic features of neurodegenerative diseases is a main cause of the lack of effective treatments. The MPTP-treated common marmoset monkey can bridge this gap by providing an appropriate animal model for construct, face and predictive validity. The neurotoxin MPTP causes selective cell death in the dopamine neurons. However, there is still a debate about the level of discomfort in the MPTP primate model. Refinement of the MPTP marmoset model-by lowering the dosage and increasing the interval-prevents the interference of direct effects of the toxin MPTP on clinical signs that might have an impact on the outcome of the result. This will also improve the discomfort for the animal as the progression of the clinical features develop slowly over time, which also mimicking the human counterpart of PD. Finetuning of the MPTP-induction protocol may, therefore, improve the wellbeing of the animal and development of rational, effective treatments for the multi-factorial pathogenic mechanisms of PD.