Redefining the hypotheses driving Parkinson's diseases research

Area of Science:

• Neuroscience
• Genetics
• Pathology

Background:

• Current Parkinson's disease (PD) research primarily focuses on central nervous system pathology.
• Growing evidence suggests PD comprises multiple diseases with diverse environmental, genetic, and comorbid factors.
• Peripheral tissues and non-neuronal cells are increasingly implicated in PD development.

Purpose of the Study:

• To challenge the view of Parkinson's disease as a single entity.
• To highlight how focusing on neuronal pathology limits understanding of PD's multiple origins and etiologies.
• To advocate for a shift towards biologically defined diseases for improved patient stratification and therapeutic development.

Main Methods:

• Review of current research on Parkinson's disease etiology and pathology.
• Discussion of the limitations of using neuronal pathology as a singular phenotype.
• Proposal for a new diagnostic and stratification approach based on distinct biological diseases.

Main Results:

• Considering PD as a single entity hinders understanding of its diverse molecular mechanisms and origins.
• A unified approach to PD overlooks the potential for multiple causative pathways and individual disease trajectories.
• The existence of distinct diseases within the spectrum of PD implies no single biomarker or treatment will be effective for all patients.

Conclusions:

• Parkinson's disease should be redefined as a collective of distinct diseases, moving away from clinical definitions.
• Biologically defined diseases are crucial for informative patient stratification.
• N-of-one clinical trial designs offer an unbiased approach to reclassifying PD into individual disease entities.