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  文章来源:自动化研究所 发布时间:2014-11-14 【字号: 小  中  大   

  题  目: Challenges and opportunities in drug discovery for neurodegenerative diseases 

  讲座人: 清华大学医学院 鲁白教授

  时  间: 2014年11月19日14:30-15:30

  地  点: 中国科学院自动化研究所智能化大厦三层第二会议室


  Despite huge progresses in neuroscience research, the number of approved drugs remains unchanged. Neurodegeneration (ND) is one of the most challenging areas in drug discovery. This is not only because brain is the most complex organ in the body, but also there is significant shortage of knowledge on disease biology. For example, the etiology of Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) is far from understood. Central Nervous System (CNS) drugs are known to have high attrition rate. Compared with other medicines, CNS drugs need to pass blood-brain barriers, a daunting task for drug development. Moreover, there is no good animal model that could be used to monitor disease progression or drug efficacy. In addition, lack of genuine biomarker and good clinical readout for AD or PD makes it extremely challenging for prove of concept (PoC) studies in human.

  To meet the challenges in ND drug discovery, many different approaches have been attempted in the academia and biopharmaceutical industry. Increasing evidence suggests that synapse and circuit dysfunctions underlying the pathophysiology of major brain illnesses. Studies of BDNF, the best known “synaptogenic” molecule proven in human, may pave the way for a paradigm shift in treating psychiatric disorders. Emerging evidence on BDNF regulation of memory and emotion, the impact of BDNF genotype on psychiatric endophenotypes, and the progress in tools to measure synaptic dysfunction in humans all suggest that time is ripe to target synaptic repair by the BDNF pathway in the clinic. In this talk, I will highlight evidence for BDNF regulation of synaptic plasticity and synaptogenesis, its role in cognitive functions such as memory and extinction. I will then discuss our recent work on translating BDNF biology into clinic. Specifically, I will talk about 1) efforts in developing measures of synaptic changes in human brain in vivo; 2) possibilities in using BDNF val/met polymorphism for patient stratification in clinical trials. Through experimental medicine in humans, we hope that a paradigm-shifting “synaptic repair” strategy will bring innovative medicines for the treatment of psychiatric diseases.


  Bai Lu received his undergraduate training at East China Normal Univ. in Shanghai, and did his Ph.D. work at Cornell Univ. Medical College in New York. After postdoctoral training with the Nobel laureate Paul Greengard at Rockefeller Univ., he became an Assistant Professor at Roche Institute of Molecular Biology/Columbia Univ. He joined National Institutes of Health (NIH) in 1996, and became the Chief of the Neural Development and Plasticity Section in 2001 (tenured). In 2004, he was named the Associate Director of Gene, Cognition and Psychosis Program (GCAP), the largest translational medicine program at NIH at that time. Dr. Lu was recruited to the GlaxoSmithKlein (GSK) R&D Center in China in July, 2009. At GSK R&D China, Dr. Lu was responsible for overall biology vision and strategy, neurodegeneration drug discovery, innovative clinical research using experimental medicine, internal discovery engine for exploratory research, external collaborations with academic institutions, non-profit foundations, and other business entities. In Oct., 2013, Dr. Lu becomes the Executive vice Dean, in charge of Tsinghua Univ. Medical School.

  Dr. Bai Lu pioneered research in the role of neurotrophins in synapse development and plasticity, and is credited for several major discoveries: 1) discovery of BDNF regulation of LTP, a cellular model for memory; 2) identification of a SNP that impacts BDNF secretion and short-term memory in human; 3) elucidation extracellular cleavage of proBDNF to mature BDNF and its role in long-term synaptic plasticity; 4) demonstration of the opposing roles of proBDNF and mature BDNF in synaptic plasticity, leading to a “Yin-Yang” hypothesis of neurotrophin actions; 5) revealing the functional role of activity-dependent BDNF transcription. Dr. Lu’s current research focuses on neural circuits underlying cognitive functions and neurodegenerative and psychiatric diseases, translational medicine, molecular pathways underlying synaptic function and neural repairs, and drug discovery based on neurotrophin pathways. He received a number of distinguished awards, including the Mathilde Solowey Award in 2003, and he was named by Thomson Reuters in 2014 as one of World’s Highly Cited Researchers, the only one in the neuroscience category named in China. 

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