Genotype-driven therapeutic developments in Parkinson’s disease

Molecular Medicine

Jannik Prasuhn¹  Norbert Brüggemann¹ 

[1] Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany;Institute of Neurogenetics, University of Lübeck, Lübeck, Germany;Center of Brain, Behavior and Metabolism, University of Lübeck, Lübeck, Germany;

关键词: Parkinson’s disease;    SNCA;    GBA;    LRRK2;    PRKN (Parkin);    PINK1;    Translational;    Monogenic;    Genetic;    Therapy;    Treatment;   

DOI  :  10.1186/s10020-021-00281-8

来源: Springer

【 摘 要 】

BackgroundRemarkable 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 manuscriptIn 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.ConclusionsThe 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.

【 授权许可】

CC BY