Novel models for Parkinson’s disease and their impact on future drug discovery

ABSTRACT

Introduction: Parkinson’s disease is a progressive neurodegenerative disease that affects millions of elderly individuals worldwide. Despite intensive efforts dedicated to find a better treatment, the pathogenesis of Parkinson’s Disease remains unknown. In search for a better therapy for the disease, several new in vivo and in vitro models of Parkinson´s disease have been developed in recent times.

Areas covered: The authors provide an outline of the various traditional models of Parkinson´s disease and address those that have been recently generated. They also discuss the utility of these models for the identification of drugs of potential therapeutic value for Parkinson´s Disease patients. From the cell based models and the well-known toxin-based animal models, to the recent genetic models and the increasingly used non-mammalian models, every model is worthwhile in the search for a better Parkinson´s Disease therapy.

Expert opinion: Almost 60 years after its discovery, levodopa is still the gold standard treatment for Parkinson's Disease patients. It seems unlikely that a single model can fully recapitulate the complexity of Parkinson's Disease in the same way it appears improbable that a unique treatment could relieve both the motor and non-motor symptoms of Parkinson's Disease altogether. Therefore treatment will probably require a combination of therapies.

KEYWORDS:

• Animal models
• non-motor symptoms
• Parkinson´s disease
• synuclein
• therapies
• treatment

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Article highlights

• Despite the intensive effort in the search of better treatments, Parkinson´s disease pathogenesis remains unknown.

• The use of animal models has contributed to the discovery of new therapeutic targets but none of these models cover all the aspects of the disease.

• Cell-based models and non-mammalian transgenic models of PD, even with limitations, could provide simple, fast and economic tools to test potential therapeutic drugs for PD

• Studying the pattern of transmission and propagation of α-syn aggregates in effective animal models could allow the development of biomarkers and imaging probes to monitor the progression of the disease.

• Non-motor symptoms have become increasingly important as early diagnostic markers in PD and specific models are needed to understand their pathophysiology.

• The combination of genetic PD models and novel technologies will be decisive for the advancement of disease-modifying drugs for PD.

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Additional information

Funding

This manuscript has not been funded.