Cambridge Healthtech Institute’s 5th Annual

Blood-Brain Barrier
( 血液脳関門 )

脳治療領域での可能性、新たな標的、モデル、ツール、治療薬のデリバリー

2019年6月19日~20日

Antibodies and new drugs that are promising for treating brain diseases and disorders are often limited by poor brain exposure. Research is focused on examining new ways to deliver drugs to the brain, including gene therapy and treatment of the BBB’s microvessels. CHI’s 5th Annual Blood-Brain Barrier conference strives to bring you the hottest topics and biggest opportunities in discovery and development of highly efficacious therapeutic agents against CNS disorders and innovative strategies for delivering therapies across the blood brain barrier (BBB). It will focus on the key areas of understanding BBB transport and dysfunction in disease through a series of case studies and cutting-edge research presentations. This conference will address questions surrounding BBB permeability, blood flow, translational research, and biomarkers of BBB breakdown. Special attention will be paid to in vivo models and tools that are available to investigate BBB transport and pathology in disease. The conference will also provide updates from the industry on antibody delivery and transport across the BBB.

Final Agenda

Arrive early to attend Tuesday, June 18 - Wednesday, June 19

CNS Targets and Translational Strategies

 

6月19日(水)

12:00 pm Registration Open

12:00 Bridging Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:30 Transition to Plenary


12:50 PLENARY KEYNOTE SESSION

2:20 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing

疾病や負傷による病変部位発生時の血液脳関門

3:05 Chairperson’s Remarks

Nathalie Y.R. Agar, PhD, Associate Professor, Neurosurgery, Brigham and Women’s Hospital

3:10 Molecular Mechanisms Governing the Formation and Regulation of the Blood Brain Barrier

Gu_ChenguaChenghua Gu, DVM & PhD, Professor of Neurobiology, Harvard Medical School

Transcytosis is actively inhibited in the CNS endothelial cells for BBB integrity. We identify that Mfsd2a acts at the BBB to regulate a specific vesicular trafficking pathway, caveolae-mediated transcytosis, in CNS endothelial cells by suppressing caveolae pit formation and cargo uptake at the plasma membrane. The lipids transported by Mfsd2a establish a unique lipid environment that inhibits caveolae vesicle formation in CNS endothelial cells to suppress transcytosis and ensure BBB integrity.

3:40 Integrated Mapping of Pharmacokinetics and Pharmacodynamics in Brain Tumors

Agar_NathalieNathalie Y.R. Agar, PhD, Associate Professor, Neurosurgery, Brigham and Women’s Hospital

We discuss time-dependent processing artifacts, underscoring the importance of immediate analysis. ivLESA-MS represents a rapid in vitro metabolomic method, which precludes the need for quenching, cell harvesting, sample preparation, and chromatography, significantly shortening preparation and analysis time while minimizing processing artifacts.

4:10 Molecular Insight into Assessment of Unbound Drug Concentration in Brain Regions of Patients with Alzheimer’s Disease

Loryan_IrenaIrena Loryan, PhD, Researcher, Department of Pharmaceutical Biosciences, Translational PKPD, Uppsala University

For preclinical and clinical assessment of therapeutically relevant unbound brain concentrations, the pharmacokinetic parameter fraction of unbound drug in the brain is commonly used to compensate total concentration for nonspecific brain tissue binding (BTB). The talk will be focused on studies providing evidence, with potential molecular mechanisms, of regional differences in drug BTB in rats and humans, opposing currently established assumptions on similar BTB between species, regions, and Alzheimer’s disease.

4:40 Sponsored Presentation (Opportunity Available)

5:10 Networking Reception in the Exhibit Hall with Poster Viewing

6:05 Close of Day


5:45 Dinner Short Course Registration

6:15 Dinner Short Course*

*Separate registration required .

6月20日(木)

7:15 am Registration Open

7:15 Breakout Discussion Groups with Continental Breakfast

ドラッグデリバリーと分子輸送:前臨床研究と臨床研究の最新動向

8:10 Chairperson’s Remarks

Danica Stanimirovic, MD, PhD, Director, Translational Bioscience Department, Human Health Therapeutics Portfolio, National Research Council of Canada

8:15 Utilizing Block Copolymers as Therapeutic Agents to Mitigate BBB Disruption

Samira M. Azarin, PhD, Assistant Professor, Department of Chemical Engineering and Materials Science, University of Minnesota

8:45 Platform Technology for Treatment of Brain Disorders with Blood-Brain Barrier Penetrating Igg-Fusion Proteins: Preclinical and Clinical Update

boado_rubenRuben Boado, PhD, Vice President, Research & Development/Co-Founder, ArmaGen, Inc.

Protein therapeutics can be re-engineered as brain penetrating IgG-bifunctional fusion proteins for the treatment of CNS disorders. The IgG domain targets a specific endogenous receptor-mediated transporter system within the BBB, i.e. human insulin receptor (HIR). The therapeutic domain of the fusion protein exerts the pharmacological effect in the brain once across the BBB. Pre-clinical and first in human proof of concept phase II clinical trial in Hurler disease will be discussed.

9:15 KEYNOTE PRESENTATION: Blood-Brain Barrier-Crossing Single-Domain Antibodies Targeting IGF1R: Mechanism of Action and Preclinical Assessment

Stanimirovic_DanicaDanica Stanimirovic, MD, PhD, Director, Translational Bioscience Department, Human Health Therapeutics Portfolio, National Research Council of Canada

Insulin growth factor 1 (IGF1) is transported across the blood-brain barrier (BBB) via a receptor-mediated transcytosis. To exploit IGF1 transcytosis route for therapeutic delivery across the BBB, single-domain antibodies (sdAb) selective for IGF1 receptor (IGF1R) were raised and optimized for binding affinity, biophysical properties, receptor binding epitopes, and species cross-reactivity. Enhanced cargo delivery across the BBB (including peptides, antibodies, enzymes and nanocarriers) was demonstrated in vitro and in animal models.

9:45 Presentation to be Announced

10:15 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 Protein Engineering For Enhanced And Sustained CNS Exposure Of Neuro-Therapeutic Antibodies

Smith_BenjaminBenjamin Smith, PhD, Scientist, Biologics Drug Discovery Biogen

The single domain antibody FC5 engages receptor-mediated transcytosis and is a promising BBB carrier. Here the humanization and stability engineering of FC5 and design of FC5 bispecifics with antibodies against neurodegenerative disease targets will be described. Enhanced BBB penetration of the bispecifics in an in vitro BBB model as well as CNS pharmacokinetics in rats and monkeys dosed at therapeutically relevant doses by systemic injections will be shown.

画像技術、前臨床研究のツール、バイオマーカー

11:30 Image-Guided Opening of the Blood Brain Barrier and Intra-Arterial Drug Delivery

Piotr_WalczakPiotr Walczak, MD, PhD, Associate Professor, Radiology, Johns Hopkins University

Endovascular neurointervention revolutionized the treatment of stroke and its applications are expanding. Intra-arterial drug delivery is a potentially excellent route for selective high concentration targeting of specific brain structures, however, blood-brain barrier (BBB) and variable biodistribution have been significant impediments to this approach. We have developed techniques for image-guided opening of the BBB and intraarterial drug delivery making the procedure precise, predictable and reproducible.

12:00 pm Differentiation of Human Pluripotent Stem Cells into High Resistance Barrier-Endothelial Cells Using Genome Editing, Genomics and Chemogenomic Library Screening Approaches

Roudnicky_FilipFilip Roudnicky, PhD, Senior Scientist, Disease Relevant Cellular Assays, F. Hoffmann-La Roche Ltd.

We will present a method to generate high-resistance barrier endothelial cells from human pluripotent stem cells (hPSCs). We have generated using genome editing a claudin 5 (CLDN5) transcriptional reporter in hPSCs to serve as a surrogate marker for high-resistance endothelial barrier. Finally, using evidence-based chemical-probe library, designed to span many molecular targets, we have screened for chemical-probes that induce CLDN5 expression in differentiated endothelial cells.

12:30 Sponsored Presentation (Opportunity Available)

1:00 Transition to Lunch

1:05 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:35 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing

中枢神経系疾患と血液脳関門の動物と細胞ベースのモデル

2:20 Chairperson’s Remarks

Piotr Walczak, MD, PhD, Associate Professor, Radiology, Johns Hopkins University

2:25 A Perfused Human Blood–Brain Barrier On-A-Chip for High-Throughput Assessment of Barrier Function and Antibody Transport

Wevers_NienkeNienke R. Wevers, MSc, Scientist, Model Development, Mimetas BV

We present a novel model of the human blood-brain barrier (BBB) in a high-throughput microfluidic system that allows parallel culture of 40 models at once. The model comprises brain endothelial cells, astrocytes, and pericytes and shows the formation of a functional barrier. Passage of an antibody targeting the human transferrin receptor was markedly higher than penetration of a control antibody, indicating that this model could support further discovery and engineering of antibody BBB-shuttle technologies.

2:55 In Vitro and in vivo Models to Evaluate P- gp and BCRP Activity in Regulating BBB Penetration

Xiao_GuangqingGuangqing Xiao, PhD, Associate Director, DMPK, Takeda

The presentation will give an overview of expression of Pgp and BCRP in BBB and BCSFB, species difference in expression, how Pgp and BCRP regulate BBB penetration, in vitro models to identify Pgp and BCRP substrates, and preclinical in vivo models to assess brain penetration, and how to use in vitro and in vivo models to identify compounds with good brain penetration.

3:25 Exploring the Utility of iPSC-Derived 3D Cortical Spheroids in the Detection of CNS Toxicity

Choi_ColinColin Choi, PhD, Scientist, Drug Safety Research and Evaluation, Takeda

Central Nervous System (CNS) toxicity is a common safety attrition for project failure during discovery and development phases due to low concordance rates between animal models and human, absence of clear biomarkers, and a lack of predictive assays. To address the challenge, we developed a CNS toxicity-detection strategy using a human iPSC-derived 3D microbrain model. Measuring viability and imaging-based functional endpoints, we conducted validation studies using compounds associated with neurodegeneration and seizure.

3:55 Linking Liver-on-a-Chip and Blood-Brain-Barrier-on-a-Chip for Toxicity Assessment

lelievre_SophieSophie Lelievre, DVM, PhD, LLM, Professor, Cancer Pharmacology, Purdue University College of Veterinary Medicine

One of the challenges to reproduce the function of tissues in vitro is the maintenance of differentiation. Essential aspects necessary for such endeavor involve good mechanical and chemical mimicry of the microenvironment. I will present examples of the management of the cellular microenvironment for liver and blood-brain-barrier tissue chips and discuss how on-a-chip devices may be linked for the integrated study of the toxicity of drugs and other molecules.

4:25 Close of Conference

Arrive early to attend Tuesday, June 18 - Wednesday, June 19

CNS Targets and Translational Strategies

 

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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更新履歴
2019/05/23
アジェンダ・スポンサー更新
2019/05/13
アジェンダ・講演者更新
2019/04/22
講演者更新
2019/04/10
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2019/03/27
講演者・スポンサー更新
2019/02/20
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