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

ABSTRACT

Introduction

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.

Areas covered

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.

Expert opinion

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.

KEYWORDS:

• α-synuclein
• disease-modifying
• kinase inhibitors
• neuroinflammation
• neuroprotection
• neurotrophins
• Parkinson’s disease

Article highlights

• The global PD pipeline counts more than 300 active programs, with about 100 late-stage clinical trials ongoing.

• One hundred and thirty-seven drug development efforts are focusing on targets with disease-modifying potential, not including gene and cell therapies.

• Alpha synuclein is a prominent target. The number of α-synuclein-targeting agents and approaches is considerable, including active and passive immunotherapy (vaccination and monoclonal antibodies, respectively) as well as new molecular entities.

• The most advanced novel disease-modifying programs are monoclonal antibodies against α-synuclein, currently being tested in Phase 2 trials and Exenatide in Phase 3.

• Beyond α-synuclein modulating agents, potential disease-modifying therapies include kinase inhibitors, neurotrophic factors, neuroprotective and anti-neuroinflammatory agents and various other new targets.

Declaration of interest

The authors of this manuscript are employees of Zambon S.p.A. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by Zambon S.p.A.