Perspective: cell death mechanisms and early diagnosis as precondition for disease modification in Parkinson’s disease: are we on the right track?

ABSTRACT

Introduction

Current research paradigms on biomarkers for chronic neurodegenerative diseases, such as Parkinson’s disease, focus on identification of reliable, easy-to-apply tools for diagnostic screening and progression assessment.

Areas covered

This perspective discusses possible misconceptions of biomarker research in chronic neurodegeneration from a clinician’s view based on a not systematic literature search. Multifactorial disease triggers, heterogeneity of symptom and their progression are main reasons for the still missing availability of biomarkers.

Expert opinion

Onset of chronic neurodegenerative disease entities may probably result from a decompensated endogenous repair machinery in the central nervous system, for example the neogenin receptor associated repulsive guidance molecule pathway. Future clinical research is warranted on these repair structures and aim to identify markers for the imbalance between damage and repair, which hypothetically contributes to generation of disease. An assignment to a specific chronic neurodegenerative disease entity probably appears to be secondary. Decryption of probable molecular signals of an impaired repair potential will enable an earlier diagnosis, better monitoring of disease progress and of treatment response. This concept will hopefully provide better preconditions for prevention, cure or therapeutic beneficial disease modification. These unmet therapeutic needs may be achieved for example via antagonism of repulsive guidance molecule A.

KEYWORDS:

• Parkinson’s disease
• non-motor symptoms
• motor symptoms
• repair
• repulsive guidance molecule A
• neogenin

Article highlights

• Cure or disease modification are unmet needs in chronic neurodegeneration, such as Parkinson’s disease.

• Diagnosis of Parkinson’s disease is relative late in the disease course due to various, interacting factors.

• Frequent reasons for this diagnostic delay are multifactorial disease origins, personality features, heterogeneity of symptoms, variability of disease mechanisms and their progression, mainly.

• Early diagnostic markers for the disease entity Parkinson’s disease do not exist.

• Search for not disease specific biomarkers, which reflect dysfunction in the existing, endogenous repair system in the peripheral and central nervous system, appears to be an alternative, promising concept.

• Research should shift to markers of the neurodegeneration generating imbalance between repair and damage, i.e. in the repulsive guidance molecule A pathway.

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.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.