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Leucine-rich repeat kinase 2 biomarkers for Parkinson's disease
1Faculty of Medicine and Health and the Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia.
Abstract:
Leucine-rich repeat kinase 2 (LRRK2) has emerged as a promising therapeutic target for the treatment of neurodegenerative Parkinson's disease (PD). Data from a multitude of pre-clinical models are supportive of a potential role for LRRK2 therapies to ameliorate cellular dysfunctions found in PD, and small molecules to inhibit LRRK2 kinase activity, as well as antisense oligonucleotides to target the protein itself, are in clinical trials. Despite this, exactly how LRRK2 contributes to PD pathogenesis remains to be determined, and definitive biomarkers to track LRRK2 function are still required. Such biomarkers can be useful for monitoring the pharmacodynamic response of LRRK2 therapeutics and/or understanding the relationship between LRRK2 and the clinical progression of PD. Moreover, biomarkers that can identify increased LRRK2 levels or activity beyond just carriers of pathogenic LRRK2 mutations will be important for expanding LRRK2 therapeutics to other PD populations. This review summarizes recent findings regarding biomarkers of LRRK2.
Insights
Biomarkers are needed to track Leucine-rich repeat kinase 2 (LRRK2) function in Parkinson's disease (PD) research. This review covers recent findings on LRRK2 biomarkers for therapeutic development and understanding PD progression.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Leucine-rich repeat kinase 2 (LRRK2) is a key therapeutic target for Parkinson's disease (PD).
- Pre-clinical models suggest LRRK2 therapies can improve cellular dysfunction in PD.
- Small molecules and antisense oligonucleotides targeting LRRK2 are in clinical trials.
Purpose of the Study:
- To review recent findings on biomarkers for Leucine-rich repeat kinase 2 (LRRK2).
- To highlight the need for biomarkers to monitor LRRK2 therapeutic response and PD progression.
- To discuss biomarkers for identifying increased LRRK2 levels/activity in broader PD populations.
Main Methods:
- Literature review of recent studies on LRRK2 biomarkers.
- Analysis of current therapeutic strategies targeting LRRK2.
- Synthesis of data on the role of LRRK2 in Parkinson's disease pathogenesis.
Main Results:
- LRRK2 kinase inhibitors and antisense oligonucleotides are under clinical investigation for PD.
- A clear understanding of LRRK2's role in PD pathogenesis is still lacking.
- Definitive biomarkers for tracking LRRK2 function are required for clinical applications.
Conclusions:
- Biomarkers are crucial for evaluating LRRK2-targeted therapies in Parkinson's disease.
- Identifying biomarkers beyond pathogenic mutations can expand therapeutic reach.
- Further research into LRRK2 biomarkers will advance PD treatment strategies.
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