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Review
. 2020 Jun 16;10(6):912.
doi: 10.3390/biom10060912.

The Future of Targeted Gene-Based Treatment Strategies and Biomarkers in Parkinson's Disease

Alexia Polissidis  1 , Lilian Petropoulou-Vathi  1 , Modestos Nakos-Bimpos  1 , Hardy J Rideout  1
Affiliations
Review

The Future of Targeted Gene-Based Treatment Strategies and Biomarkers in Parkinson's Disease

Alexia Polissidis et al. Biomolecules. .

Abstract

Biomarkers and disease-modifying therapies are both urgent unmet medical needs in the treatment of Parkinson's disease (PD) and must be developed concurrently because of their interdependent relationship: biomarkers for the early detection of disease (i.e., prior to overt neurodegeneration) are necessary in order for patients to receive maximal therapeutic benefit and vice versa; disease-modifying therapies must become available for patients whose potential for disease diagnosis and prognosis can be predicted with biomarkers. This review provides an overview of the milestones achieved to date in the therapeutic strategy development of disease-modifying therapies and biomarkers for PD, with a focus on the most common and advanced genetically linked targets alpha-synuclein (SNCA), leucine-rich repeat kinase-2 (LRRK2) and glucocerebrosidase (GBA1). Furthermore, we discuss the convergence of the different pathways and the importance of patient stratification and how these advances may apply more broadly to idiopathic PD. The heterogeneity of PD poses a challenge for therapeutic and biomarker development, however, the one gene- one target approach has brought us closer than ever before to an unprecedented number of clinical trials and biomarker advancements.

Keywords: GBA; LRRK2; Parkinson’s disease; alpha-synuclein; biomarker; disease-modifying; glucocerebrosidase.

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Conflict of interest statement

All authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Timeline of milestone discoveries related to the three main genetic PD targets; a-synuclein, LRRK2 and GBA. DLB, Dementia with Lewy bodies; GBA, P-Glucocerebrosidase {Gcase) gene; LRRK2, Leucine—rich repeat kinase 2; PD, Parkinson’s disease; SNCA, α-synuclein gene; * Gaucher disease is a lysosomal storage disorder caused by biallelic GBA mutations.
Figure 2
Figure 2
Mechanisms of action of the potential therapeutic compounds currently in clinical trials. As, Alpha-synuclein; ASO, Anti-sense oligonucleotides; GlcCer, Glucosylceramide; LRRK2, Leucine-rich repeat kinase 2.
See this image and copyright information in PMC

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