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Review
. 2020 Oct;17(4):1366-1377.
doi: 10.1007/s13311-020-00894-7.

Therapy of Parkinson's Disease Subtypes

Connie Marras  1 , K Ray Chaudhuri  2 , Nataliya Titova  3   4 , Tiago A Mestre  5
Affiliations
Review

Therapy of Parkinson's Disease Subtypes

Connie Marras et al. Neurotherapeutics. 2020 Oct.

Abstract

Early descriptions of subtypes of Parkinson's disease (PD) are dominated by the approach of predetermined groups. Experts defined, from clinical observation, groups based on clinical or demographic features that appeared to divide PD into clinically distinct subsets. Common bases on which to define subtypes have been motor phenotype (tremor dominant vs akinetic-rigid or postural instability gait disorder types), age, nonmotor dominant symptoms, and genetic forms. Recently, data-driven approaches have been used to define PD subtypes, taking an unbiased statistical approach to the identification of PD subgroups. The vast majority of data-driven subtyping has been done based on clinical features. Biomarker-based subtyping is an emerging but still quite undeveloped field. Not all of the subtyping methods have established therapeutic implications. This may not be surprising given that they were born largely from clinical observations of phenotype and not in observations regarding treatment response or biological hypotheses. The next frontier for subtypes research as it applies to personalized medicine in PD is the development of genotype-specific therapies. Therapies for GBA-PD and LRRK2-PD are already under development. This review discusses each of the major subtyping systems/methods in terms of its applicability to therapy in PD, and the opportunities and challenges designing clinical trials to develop the evidence base for personalized medicine based on subtypes.

Keywords: Parkinson’s disease; subtypes; therapy.

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Figures

Fig. 1
Fig. 1
Integration of subtyping (endophenotyping) into personalized medicine in Parkinson’s disease, adapted from [119]. Patients with Parkinson’s disease can be clinically subtyped anchored on the dominant nonmotor symptoms (NMS) evident in the denovo or early motor stage using specific biomarkers (imaging or genetic) where available. The resulting subtype can then be clinically managed using a subtype-specific treatment approach which incorporates several strands of personalized medicine and multi-disciplinary input as well as monitoring with patient related outcome measures (PRO)
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