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Review
. 2022 Sep;129(9):1133-1153.
doi: 10.1007/s00702-022-02520-6. Epub 2022 Jun 13.

Disease modification in Parkinsonism: obstacles and ways forward

M Höllerhage #  1 , M Klietz #  1 , G U Höglinger  2
Affiliations
Review

Disease modification in Parkinsonism: obstacles and ways forward

M Höllerhage et al. J Neural Transm (Vienna). 2022 Sep.

Abstract

To date, the diagnoses of Parkinson syndromes are based on clinical examination. Therefore, these specific diagnoses are made, when the neuropathological process is already advanced. However, disease modification or neuroprotection, is considered to be most effective before marked neurodegeneration has occurred. In recent years, early clinical or prodromal stages of Parkinson syndromes came into focus. Moreover, subtypes of distinct diseases will allow predictions of the individual course of the diseases more precisely. Thereby, patients will be enrolled into clinical trials with more specific disease entities and endpoints. Furthermore, novel fluid and imaging biomarkers that allow biochemical diagnoses are under development. These will lead to earlier diagnoses and earlier therapy in the future as consequence. Furthermore, therapeutic approaches will take the underlying neuropathological process of neurodegenerative Parkinson syndromes more specific into account. Specifically, future therapies will target the aggregation of aggregation-prone proteins such as alpha-synuclein and tau, the degradation of pathological aggregates, and the spreading of pathological protein aggregates throughout the brain. Many of these approaches are already in (pre)clinical development. In addition, anti-inflammatory approaches are in development. Furthermore, drug-repurposing is a feasible approach to shorten the developmental process of new drugs.

Keywords: Biomarkers; Disease modification; Multiple System Atrophy; Parkinson’s disease; Prodromal Parkinsonism; Progressive Supranuclear Palsy.

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Conflict of interest statement

The authors have no conflict of interest to report.

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