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Genotype-driven therapeutic developments in Parkinson’s disease

BACKGROUND: Remarkable advances have been reached in the understanding of the genetic basis of Parkinson’s disease (PD), with the identification of monogenic causes (mPD) and a plethora of gene loci leading to an increased risk for idiopathic PD. The expanding knowledge and subsequent identification...

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Autores principales: Prasuhn, Jannik, Brüggemann, Norbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056568/
https://www.ncbi.nlm.nih.gov/pubmed/33874883
http://dx.doi.org/10.1186/s10020-021-00281-8
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author Prasuhn, Jannik
Brüggemann, Norbert
author_facet Prasuhn, Jannik
Brüggemann, Norbert
author_sort Prasuhn, Jannik
collection PubMed
description BACKGROUND: Remarkable advances have been reached in the understanding of the genetic basis of Parkinson’s disease (PD), with the identification of monogenic causes (mPD) and a plethora of gene loci leading to an increased risk for idiopathic PD. The expanding knowledge and subsequent identification of genetic contributions fosters the understanding of molecular mechanisms leading to disease development and progression. Distinct pathways involved in mitochondrial dysfunction, oxidative stress, and lysosomal function have been identified and open a unique window of opportunity for individualized treatment approaches. These genetic findings have led to an imminent progress towards pathophysiology-targeted clinical trials and potentially disease-modifying treatments in the future. MAIN BODY OF THE MANUSCRIPT: In this review article we will summarize known genetic contributors to the pathophysiology of Parkinson’s disease, the molecular mechanisms leading to disease development, and discuss challenges and opportunities in clinical trial designs. CONCLUSIONS: The future success of clinical trials in PD is mainly dependent on reliable biomarker development and extensive genetic testing to identify genetic cases. Whether genotype-dependent stratification of study participants will extend the potential application of new drugs will be one major challenge in conceptualizing clinical trials. However, the latest developments in genotype-driven treatments will pave the road to individualized pathophysiology-based therapies in the future.
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spelling pubmed-80565682021-04-20 Genotype-driven therapeutic developments in Parkinson’s disease Prasuhn, Jannik Brüggemann, Norbert Mol Med Review BACKGROUND: Remarkable advances have been reached in the understanding of the genetic basis of Parkinson’s disease (PD), with the identification of monogenic causes (mPD) and a plethora of gene loci leading to an increased risk for idiopathic PD. The expanding knowledge and subsequent identification of genetic contributions fosters the understanding of molecular mechanisms leading to disease development and progression. Distinct pathways involved in mitochondrial dysfunction, oxidative stress, and lysosomal function have been identified and open a unique window of opportunity for individualized treatment approaches. These genetic findings have led to an imminent progress towards pathophysiology-targeted clinical trials and potentially disease-modifying treatments in the future. MAIN BODY OF THE MANUSCRIPT: In this review article we will summarize known genetic contributors to the pathophysiology of Parkinson’s disease, the molecular mechanisms leading to disease development, and discuss challenges and opportunities in clinical trial designs. CONCLUSIONS: The future success of clinical trials in PD is mainly dependent on reliable biomarker development and extensive genetic testing to identify genetic cases. Whether genotype-dependent stratification of study participants will extend the potential application of new drugs will be one major challenge in conceptualizing clinical trials. However, the latest developments in genotype-driven treatments will pave the road to individualized pathophysiology-based therapies in the future. BioMed Central 2021-04-19 /pmc/articles/PMC8056568/ /pubmed/33874883 http://dx.doi.org/10.1186/s10020-021-00281-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review
Prasuhn, Jannik
Brüggemann, Norbert
Genotype-driven therapeutic developments in Parkinson’s disease
title Genotype-driven therapeutic developments in Parkinson’s disease
title_full Genotype-driven therapeutic developments in Parkinson’s disease
title_fullStr Genotype-driven therapeutic developments in Parkinson’s disease
title_full_unstemmed Genotype-driven therapeutic developments in Parkinson’s disease
title_short Genotype-driven therapeutic developments in Parkinson’s disease
title_sort genotype-driven therapeutic developments in parkinson’s disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056568/
https://www.ncbi.nlm.nih.gov/pubmed/33874883
http://dx.doi.org/10.1186/s10020-021-00281-8
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