Therapeutic innovation in Parkinson's disease: a 2020 update on disease-modifying approaches

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting more than 10 million patients worldwide. Despite increasing improvements in disease management, a huge medical need still exists as its relentless progression cannot be delayed by current treatments. Therefore, scientists, clinicians, and pharmaceutical companies are hunting new drugs with 'disease-modifying' properties.

This review concentrates on new therapeutics - excluding cell and gene therapies - under investigation for PD with 'disease-modifying' potential. This is a global, comprehensive picture of the current innovative drug pipeline, where the main preclinical and clinical data available are provided. Drug candidates presented include α-synuclein modulating agents, neuroprotective agents and neuroinflammation modulators, kinase modulators, neurotrophic factors, and drugs acting on emerging targets.

There is excitement for agents with 'disease-modifying' properties and the authors found more than 130 assets, not including cell and gene therapies under investigation - most of them still in preclinical development - meaning that the science is progressing multiple, diverse new opportunities. Many limitations hamper the successful development of these drug candidates such as the translational accuracy of preclinical models, the current clinical development paradigm as well as the lack of biomarkers to be used in diagnosis and therapy management.