Precision medicine for disease modification in Parkinson’s disease

時間地點:02:00 pm, Dec 06 (Wed), 2023; R1-B1122 Conference Room

研討講者:Chin-Hsien Lin, Ph.D.

November 28, 2023


Parkinson’s disease (PD) is a common neurodegenerative disorder in aging society affecting >1% of the population ≥60 years of age and the affected number will be doubled by 2030. PD is characterized by motor deficits and a wide variety of non-motor symptoms. Neuropathologically, PD is also characterized by dopaminergic neuronal alpha -synuclein aggregations named Lewy body and the pathological alpha-synuclein can transmit from cell to cell in a prion-like fashion to promote the neurodegenerative process of this disease. Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification. It has been suggested that the heterogeneity of PD is a major contributing factor to the failure of disease modification trials, and that it is unlikely that a single treatment will be effective in all patients. Precision medicine, using drugs designed to target the pathophysiology in a manner that is specific to each individual with PD, has been suggested as a way forward. Given the likely entry of several classes of mechanism-targeted therapies into early human clinical trials, the identification of easily accessible biomarkers that identify the early-stage of the disease and reflect disease severity in PD is urgently needed. In this speech, I am going to update the recent advances in the development of biofluid-based PD biomarkers from different aspects, including variable forms of a-synuclein, tau, and neurofilament light chain. Pathological α-synuclein forms derived from neuronal extracellular vesicles and the real-time quaking-induced conversion (RT-QuIC) analysis of CSF have high sensitivity and specificity for the detection of misfolded α-synuclein in patients with PD. PD patients can therefore be stratified according to the biomarkers and whether they carry one of the risk variants associated with elevated PD risk. The combination of multimodal biomarkers will greatly improve the diagnostic accuracy, assist the differential diagnosis with various Parkinsonian syndromes and facilitate the implementation of personalized medicine for PD in the near future. This talk will assess current treatment strategies targeted specific PD-causative genes using different biomarkers and potential future implications.

Chin-Hsien Lin, Ph.D.

Department of Neurology

National Taiwan University Hospital

Chin-Hsien Lin, Ph.D.

Dr. Chin-Hsien Lin graduated from College of Medicine, National Taiwan University, and received her neurological residency training in National Taiwan University Hospital (NTUH). She received her PhD training from Institute of Molecular Biology, Academia Sinica. She received post-doctoral fellowship training in the Center for University of British Columbia, Canada (Dr. Matthew Farrer’s laboratory).

Dr. Lin is now a professor in Department of Neurology, National Taiwan University Hospital. Her main academic interests include genetic and molecular biology studies of Parkinson’s disease and related neurodegenerative disorders. She investigated the molecular mechanisms of mutations of Parkinson’s disease or dystonia causative genes in neuronal degeneration by using cellular and animal model systems. She was elected to join the leadership program (LEAP) of international Movement Disorder Society (MDS)-AOS section in 2015. She is now the president of Taiwan Movement Disorders Society and is also joining several committees of MDS, including executive committee of the MDS-AOS section, evidence-based medicine (EBM) and basic neuroscience committees of MDS.

Honors and Awards:

2017  Young Investigator Winner Award of Yungshin Lee Tien-Te Biomedical Foundation.  

2019  FUTEX Technology Award of Ministry of Science and Technology (MOST)

2021  Scientific Paper Award, Far Eastern Y.Z. Hsu Science and Technology

           Memorial Foundation

           Distinguished Research Award, National Taiwan University Hospital

           Ministry of Science and Technology (MOST) Outstanding Research Award

Selected Publications:

1.          Chen SJ, et al. Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Parkinson Disease Patients. Neurology. 2022 doi: 10.1212/WNL.0000000000013225.

2.          Lin CH et al. Mild chronic colitis triggers Parkinsonism in LRRK2 mutant mice through activating TNF-α pathway. Movement Disorders 2021, Dec 17. doi: 10.1002/mds.28890.

3.          Chang KH, et al., In vitro genome editing rescues parkinsonism phenotypes in induced pluripotent stem cells-derived dopaminergic neurons carrying LRRK2 p.G2019S mutation. Stem Cell Research & Therapy 2021 Sep 22;12(1):508. doi: 10.1186/s13287-021-02585-2.

4.     Lin CH, et al., Mitochondrial UQCRC1 mutations cause autosomal dominant parkinsonism with polyneuropathy. Brain 2020 Dec 5;143(11):3352-3373.