Therapy of Parkinson’s Disease Subtypes

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...

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Bibliographic Details
Published in:Neurotherapeutics 2020-10, Vol.17 (4), p.1366-1377
Main Authors: Marras, Connie, Chaudhuri, K. Ray, Titova, Nataliya, Mestre, Tiago A.
Format: Article
Language:English
Subjects:
Biomarkers
Biomedical and Life Sciences
Biomedicine
Clinical trials
Gait
Gait Disorders, Neurologic - classification
Gait Disorders, Neurologic - diagnosis
Gait Disorders, Neurologic - genetics
Gait Disorders, Neurologic - therapy
Genotypes
Hereditary diseases
Humans
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics
LRRK2 protein
Motor Disorders - classification
Motor Disorders - diagnosis
Motor Disorders - genetics
Motor Disorders - therapy
Movement disorders
Neurobiology
Neurodegenerative diseases
Neurology
Neurosciences
Neurosurgery
Parkinson Disease - classification
Parkinson Disease - diagnosis
Parkinson Disease - genetics
Parkinson Disease - therapy
Parkinson's disease
Phenotypes
Precision medicine
Review
Tremor
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Description
Summary: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.
ISSN:1933-7213
1878-7479
1878-7479
DOI:10.1007/s13311-020-00894-7