シンポジウム5：Parkinson病の新規薬物療法：最新の動向と展望
プレシジョンメディスンの現状と展望
2021 年 38 巻 3 号 p. 330-335
詳細
2021 年 38 巻 3 号 p. 330-335
Precision medicine is a medical model that provides each patient with more customized medical decision, treatments and practices based on detailed information including individual genetic information using the latest technology, instead of a one–drug–fits–all model. We report the current status and prospects of precision medicine for monogenic form of Parkinson's disease (PD).
The outcome of deep brain stimulation (DBS) is generally favorable, with improved motor function and decreased levodopa equivalent daily dose in PD patients with PRKN, LRRK2 mutations. Around 30% of PD patients with GBA mutations had poor outcomes in motor function and progressive cognitive decline was reported after DBS.
A clinical trial (MOVES–PD) using Venglustat, a small–molecule glucosylceramide synthase inhibitor, has begun in PD patients with GBA mutations. The Phase II trial of venglustat failed to meet its primary endpoint and this study was discontinued.
In PLA2G6 (PARK14) deficient Drosophila, lipid replacement therapy corrected the brain lipid composition suppressed dopaminergic neurodegeneration and α–synuclein aggregation, and improved motor function in Drosophila. The dietary manipulation of fatty acids over a long time period could change brain lipid components to prevent α–synuclein aggregation in PD patients with PLA2G6 mutations.
In CHCHD2 (PARK22) deficient Drosophila, the light–dependent activation of mitochondrial proton–motive force using Delta–rhodopsin to recover the function of mitochondria, improved α–synuclein aggregation, DA neuronal loss, and motor behaviors, suggesting that maintaining the mitochondrial proton–motive force may serve as a therapeutic strategy for PD.
Finally, we introduce “PD Registry” in our department. We are planning to recruit hundreds of PD patients, and register a clinical information with many clinical scales, advanced MRI information and genetic information, and started to create a database. Using network science and artificial intelligence, we aim to elucidate the objective evaluation method of clinical subtypes of PD, and to develop precision medicine.
