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Pharmacodynamic Biomarkers for Emerging LRRK2 Therapeutics

Genetic studies have identified variants in the LRRK2 gene as important components of Parkinson’s disease (PD) pathobiology. Biochemical and emergent biomarker studies have coalesced around LRRK2 hyperactivation in disease. Therapeutics that diminish LRRK2 activity, either with small molecule kinase...

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Detalles Bibliográficos
Autores principales: Kelly, Kaela, West, Andrew B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438883/
https://www.ncbi.nlm.nih.gov/pubmed/32903744
http://dx.doi.org/10.3389/fnins.2020.00807
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author Kelly, Kaela
West, Andrew B.
author_facet Kelly, Kaela
West, Andrew B.
author_sort Kelly, Kaela
collection PubMed
description Genetic studies have identified variants in the LRRK2 gene as important components of Parkinson’s disease (PD) pathobiology. Biochemical and emergent biomarker studies have coalesced around LRRK2 hyperactivation in disease. Therapeutics that diminish LRRK2 activity, either with small molecule kinase inhibitors or anti-sense oligonucleotides, have recently advanced to the clinic. Historically, there have been few successes in the development of therapies that might slow or halt the progression of neurodegenerative diseases. Over the past few decades of biomedical research, retrospective analyses suggest the broad integration of informative biomarkers early in development tends to distinguish successful pipelines from those that fail early. Herein, we discuss the biomarker regulatory process, emerging LRRK2 biomarker candidates, assays, underlying biomarker biology, and clinical integration.
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spelling pubmed-74388832020-09-03 Pharmacodynamic Biomarkers for Emerging LRRK2 Therapeutics Kelly, Kaela West, Andrew B. Front Neurosci Neuroscience Genetic studies have identified variants in the LRRK2 gene as important components of Parkinson’s disease (PD) pathobiology. Biochemical and emergent biomarker studies have coalesced around LRRK2 hyperactivation in disease. Therapeutics that diminish LRRK2 activity, either with small molecule kinase inhibitors or anti-sense oligonucleotides, have recently advanced to the clinic. Historically, there have been few successes in the development of therapies that might slow or halt the progression of neurodegenerative diseases. Over the past few decades of biomedical research, retrospective analyses suggest the broad integration of informative biomarkers early in development tends to distinguish successful pipelines from those that fail early. Herein, we discuss the biomarker regulatory process, emerging LRRK2 biomarker candidates, assays, underlying biomarker biology, and clinical integration. Frontiers Media S.A. 2020-08-06 /pmc/articles/PMC7438883/ /pubmed/32903744 http://dx.doi.org/10.3389/fnins.2020.00807 Text en Copyright © 2020 Kelly and West. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Kelly, Kaela
West, Andrew B.
Pharmacodynamic Biomarkers for Emerging LRRK2 Therapeutics
title Pharmacodynamic Biomarkers for Emerging LRRK2 Therapeutics
title_full Pharmacodynamic Biomarkers for Emerging LRRK2 Therapeutics
title_fullStr Pharmacodynamic Biomarkers for Emerging LRRK2 Therapeutics
title_full_unstemmed Pharmacodynamic Biomarkers for Emerging LRRK2 Therapeutics
title_short Pharmacodynamic Biomarkers for Emerging LRRK2 Therapeutics
title_sort pharmacodynamic biomarkers for emerging lrrk2 therapeutics
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438883/
https://www.ncbi.nlm.nih.gov/pubmed/32903744
http://dx.doi.org/10.3389/fnins.2020.00807
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