Boston Professional Events List


Blood Brain Barrier


Date
Jun 12, 2017 - 07:00 AM - Jun 16, 04:15 PM
Organizer
CHI Conferences
Venue
Westin Copley Place
Location
10, Huntington Ave

Boston,
MA,
USA,
ZIP: 02116
Phone:

Antibodies and new drugs hold promise for treating brain diseases and disorders; however, their utility is often limited by poor penetration across the Blood Brain Barrier (BBB). CHI’s Blood Brain conference strives to bring you the hottest topics in BBB from leaders in the pharmaceutical, biotech and academic fields. We showcase the biggest opportunities for large and small molecules through cutting-edge research, case studies, panel discussions, poster presentations and breakout discussions. The third annual Blood-Brain Barrier conference will brainstorm ideas and share new research on topics such as the BBB at sites of pathology, preclinical models, imaging, tools for prediction of brain penetration, and updates from the industry on topics such as antibody delivery and vector-mediated transport across BBB.



Agenda


TUESDAY, JUNE 13

7:00 am Registration Open and Morning Coffee

UNDERSTANDING AND PREDICTION OF BRAIN PENETRATION AND TRANSPORT ACROSS THE BBB

8:25 Chairperson’s Opening Remarks

Torben Moos, Ph.D., The Faculty of Medicine, Department of Health Science and Technology, Laboratory of Neurobiology, Aalborg University

8:35 KEYNOTE PRESENTATION: Targeted Uptake and Transport of Nanocarriers at the Blood-Brain Barrier

Torben_MoosTorben Moos, Ph.D., The Faculty of Medicine, Department of Health Science and Technology, Laboratory of Neurobiology, Aalborg University

Targeted delivery of immunoliposomes containing oxaliplatin to brain capillary endothelial cells (BCECs) was studied in vitro and in vivo in the rat with the aim of quantifying nanocarrier and cargo uptake in BCECs and the remainder portion of the CNS. The study provides evidence for a preferential uptake and processing of the targeted liposomes within the BCECs. Studies are undergoing to track down the fate of the liposomes and their cargo.

9:05 Blood-Brain Barrier Targeting and Transport

Robert D. Bell, Ph.D., Senior Principal Scientist, Neurovascular Biology Lab Head, Pfizer, Inc.

9:35 But HOW Did It Affect the Brain?

Lois_LampsonLois A. Lampson, Ph.D., Associate Professor of Neurosurgery, Brigham & Women’s Hospital/Harvard Medical School

Full-sized antibodies, delivered to the blood, can affect the brain. Antibody-mediated reduction of amyloid in animal models of Alzheimer’s disease is one example, among others. Even where the effect is well-documented, its basis can be controversial: is the antibody actually working from within the brain? If so, how did it get there? If not, how was its effect on the brain achieved? Specific examples and alternatives will be compared.

10:05 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

NEW IMAGING TECHNIQUES & TOOLS

10:50 Antibody-Based PET Imaging in Mouse Models of Alzheimer’s Disease

Dag_SehlinDag Sehlin, Ph.D., Researcher, Department of Public Health/Geriatrics, Uppsala University

Due to their high specificity, antibodies are attractive in PET ligand development, but the BBB is an obstacle to antibody-based PET imaging within the CNS. By engineering antibodies in various formats to target the transferrin receptor for active brain delivery, we have enabled specific PET imaging of amyloid-beta pathology in mouse models of Alzheimer’s disease. This technique may allow imaging of CNS targets where conventional PET ligands are currently lacking.

11:20 Predicting and Optimizing the Territory of Blood-Brain Barrier Opening by Superselective Intra-Arterial Cerebral Infusion under Dynamic Susceptibility Contrast MRI Guidance

Miroslaw_JanowskiMiroslaw Janowski, M.D., Ph.D., Associate Professor, Radiology, Johns Hopkins University

Interventional neuroradiology techniques are minimally invasive and allow for superselective drug delivery to specific brain regions. The passage of most agents, however, is impaired by the blood-brain barrier (BBB). Despite its discovery over 40 years ago, hyperosmotic BBB opening (BBBO) remains highly variable, preventing its widespread implementation. Here, we report on a technique that enables the prediction and optimization of the BBBO territory using real-time MRI guidance.

Synvivo11:50 A Realistic and Dynamic 3D Tissue Model for Investigation of Blood Brain Barrier Functionality

Prabhakar_PandianPrabhakar Pandian, Ph.D., Chief Technology Officer, SynVivo, Inc.

Physiologically relevant 3D blood brain barrier (BBB) model recreates a histological slice of brain tissue in communication with endothelial cells across the BBB. Consistent with in vivo phenotype, cells cultured under dynamic flow conditions exhibit tight junction formation and functional responses. Patented architecture allows real time visualization of cellular and barrier functionality. Studies highlighting permeability of small molecules, transporters, inflammation and therapeutic screening including in vivo validation will be presented.

Neurotar  

12:05 pm Longitudinal Studies of BBB, Cells and Organelles Using a Unique in vivo Microscopy Platform

Leonard_KhirougLeonard Khiroug, Ph.D., CSO, Neurotar Ltd.

CNS cells and subcellular organelles, such as neuronal dendritic spines or glial fine processes, are best studied in their natural environment, i.e. in the intact brain of a live animal. We shall discuss several preclinical studies performed using our in vivo multiphoton imaging platform in combination with Neurotar’s proprietary device, Mobile HomeCage, which enables microscopic analysis of (sub)cellular structure and function in the brain of awake, behaving mice.

12:20 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:50 Session Break

NEW IMAGING TECHNIQUES & TOOLS (CONT.)

1:40 Chairperson’s Remarks

Robyn S. Klein, M.D., Ph.D., Director, Center for Neuroimmunology & Neuroinfectious Diseases, Department of Internal Medicine, Neurobiology, Pathology & Immunology, Washington University School of Medicine

1:50 Role of Blood-Brain Barrier Function in Alzheimer’s Disease Pathogenesis Investigated by Using a 3D Microfluidic Platform

Yoojin Shin, Ph.D., Postdoctoral Fellow, Mechanical Engineering, MIT

We have developed a physiologically relevant three-dimensional (3D) human neural cell culture model of Alzheimer’s disease (AD) with a neurovascular unit (blood brain barrier, BBB) in a microfluidic system (3D AD-BBB model). Using this model, we proposed to investigate the impact of the BBB on AD pathogenesis and to explore whether Aβ and/or toxic molecules generated from 3D cultures expressing multiple AD genes disrupt normal BBB function. In this study, we found Aβ disrupts BBB function involving permeability increase. We also found that the presence of the BBB increases cell viability in the 3D cultures, and that Interleukin-8 (IL-8) and IL-6, which are secreted from the BBB, are responsible for increased cell viability in our 3D AD models.

2:20 Development of Highly Efficient BBB Transport of Antibodies to the CNS Using in vivo Phage Display with Single Domain VNAR to the Transferrin Receptor

Frank S. Walsh, Ph.D., CEO, Ossianix

Partially enriched phage libraries to TfR1 were injected in vivo and isolated from brain parenchyma through 3 enrichment cycles. A number of hits were formatted on a Fc backbone and found to give over one log greater exposure in brain parenchyma than previous hits and produced brain/plasma ratios of over 5% at 18 hours after a single IV injection of 2 mg/kg. These VNARs, which bind with equal affinity to mouse and human TfR1, have now been formatted as bispecific agents with a variety of antibodies and give highly efficient BBB transfer at low therapeutic doses. The VNAR TfR1 panel promises to be a highly efficient method for transfer of therapeutic levels of antibody or other biologics to the CNS.

2:50 Poster Highlight Presentation: Delivery of Therapeutic Peptides Across Cellular Barriers for Type II Diabetes by Fusion to Gangliosides with Varied Acyl Chains

Daniel Chinnapen, Ph.D ., Assistant Professor of Pediatrics, Boston Children’s Hospital / Harvard Medical School

Delivery of biologics across highly selective mucosal barriers has been challenging due to their inability to internalize and cross host cells. Based on an understanding of intracellular lipid sorting, we are developing ganglioside(lipid)-fusions for the delivery of therapeutic peptides across intestinal mucosa for oral based treatment of Type II Diabetes. In vitro monolayer and in vivo mouse studies show that only peptides fused to gangliosides are absorbed and are efficacious.

3:20 Refreshment Break in the Exhibit Hall with Poster Viewing

THE BLOOD-BRAIN BARRIER AT SITES OF PATHOLOGY

4:05 Viral Sensing at the Blood-Brain Barrier

Robyn_KleinRobyn S. Klein, M.D., Ph.D., Director, Center for Neuroimmunology & Neuroinfectious Diseases, Department of Internal Medicine, Neurobiology, Pathology & Immunology, Washington University School of Medicine

Arboviruses that infect the CNS include members of the Flaviviridae (e.g., West Nile virus), and Togaviridae (Alphaviruses) families. Mechanisms exist to protect the CNS from infection with neurotropic viruses, including innate immune responses and the BBB. Our research has highlighted various mechanisms by which viruses modulate BBB function. Here we will present new data focused on mechanisms of BBB entry and dysfunction during alphavirus encephalitis.

4:35 Discovery and Validation of Novel Biomarkers for Immunotherapy Trials in AD and CAA

Fabrizio Piazza, Ph.D., Principal Investigator, iCAβ International Network Coordinator, School of Medicine, University of Milano-Bicocca

DRUG DELIVERY &TRANSPORT ACROSS BBB: UPDATES FROM THE INDUSTRY

5:05 Engineered Protein Capsules for Targeted Delivery of Drugs to the Brain

Axel H. Meyer, Ph.D., Head of Brain Delivery, Neuroscience Discovery, AbbVie GmbH & Co. KG

Engineered Protein Capsules are genome-free components of the native JC virus. Such particles have been studied as therapeutic or diagnostic tools as they can be loaded with various drugs. Here we present results on EPCs based on the JC virus as tools for brain delivery. This work is a collaborative effort between Neuway Pharma and AbbVie which is co-funded by the German Ministry for Education and Research (BMBF).

5:35 Welcome Reception in the Exhibit Hall with Poster Viewing

6:45 Close of Day

Day 1 | Day 2 | Download Brochure

WEDNESDAY, JUNE 14

7:00 am Registration Open

7:30 Interactive Breakout Discussion Groups with Continental Breakfast

This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas and active networking. Continental breakfast is available for all participants.

Are Nanoparticles Feasible for CNS Therapeutic Targeting?

Moderator: Danica Stanimirovic, M.D., Ph.D., Director, Translational Bioscience Department, Human Health Therapeutics Portfolio, National Research Council of Canada

  • What are the size limitations for nanoparticles (for BBB crossing; for distribution in the ECS)?
  • To target (with Trojan molecules) or not?
  • Type of nanoparticles (synthetic or ‘natural’ – e.g., exosomes)?
  • PK, stability vs. release? Which type of therapeutic (e.g., nucleic acid molecules, biologics, synthetic molecules)?

Is Repetitive Opening of BBB Safe?

Moderator: Miroslaw Janowski, M.D., Ph.D., Assistant Professor, Radiology, Johns Hopkins University

  • Can high-dose intra-arterial chemotherapy through open BBB be useful as much as for treatment of retinoblastoma, where it became a treatment of choice?
  • Is there a compelling need for imaging of drug concentration inside the brain tumor, including intra-arterial therapies through open BBB
  • Is repetitive opening of BBB safe?

 

DRUG DELIVERY &TRANSPORT ACROSS BBB: UPDATES FROM THE INDUSTRY(CONT.)

8:35 Chairperson’s Remarks

Danica Stanimirovic, M.D., Ph.D., Director, Translational Bioscience Department, Human Health Therapeutics Portfolio, National Research Council of Canada

8:45 Development of the BBB-Crossing, Amyloid-ß Oligomer-Targeting Therapeutic for Alzheimer’s Disease

Balu_ChakravarthyBalu Chakravarthy, Ph.D., Senior Research Officer, National Research Council Canada

An amyloid-ß (Aß) oligomer-binding peptide (ABP) was engineered to cross the blood-brain barrier using a single-domain antibody, FC5. FC5-ABP demonstrated dose- and time-dependent increase in CSF and brain exposure in mice, rats and dogs, compared to ABP alone. In AD-transgenic mice and rats, systemic injection caused an accelerated (within 4 weeks) reduction of Aß levels in CSF and brain parenchyma, illustrating importance of cross-BBB delivery of the Aß–targeting therapeutic.

9:15 Efficient Delivery of Biologics across BBB for Neurological Diseases

Denise Karaoglu HanzatianDenise Karaoglu Hanzatian, Ph.D., Principal Research Scientist, Biologics Discovery, AbbVie Bioresearch Center, AbbVie

 

 

 

 

9:45 Blood-Brain Barrier Carta Project: Novel Targets and BBB-Crossing Single-Domain Antibodies

Danica_StanimirovicDanica Stanimirovic, M.D., Ph.D., Director, Translational Bioscience Department, Human Health Therapeutics Portfolio, National Research Council of Canada

BBB Carta project is a comprehensive molecular ‘map’ of BBB cells, brain vessels and neurovascular unit. BBB Carta was used to select novel BBB-selective targets that undergo a receptor-mediated transcytosis. Single domain antibodies raised against these targets were evaluated as potential novel BBB carriers in models in vitro, and in animal studies. Some of these antibodies showed enhanced brain penetration and ability to induce central pharmacological responses after systemic exposure.

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

11:00 Treatment of Human Lysosomal Storage Disorders with Blood-Brain Barrier Penetrating IgG-Fusion Proteins

Ruben_BoadoRuben Boado, Ph.D., Vice President, Research & Development/Co-Founder, ArmaGen, Inc.

Protein therapeutics can be re-engineered as brain penetrating IgG-fusion proteins for the CNS treatment of rare disorders, like Lysosomal Storage Disorders (LSD). The IgG domain targets a specific endogenous receptor-mediated transporter system within the blood-brain barrier (BBB), such as the human insulin receptor (HIR). The protein therapeutic domain of the fusion protein exerts the pharmacological effect in brain once across the BBB. Several brain penetrating enzyme fusion proteins have been engineered for LSD. First in human Phase I/II clinical trials are in progress.

11:30 FEATURED PRESENTATION: Tackle One of the Toughest Problems in Medicine: Delivery of Biologics Across the Blood-Brain Barrier

Peo_FreskgardPer-Ola Freskgard, Ph.D., Vice Director and Senior Leader, Neuroscience, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd.

This presentation will provide a short overview of the progresses that were made over the last 5 years to identify novel antibody engineering platforms that utilizes receptor-mediated transcytosis to cross the blood-brain barrier (BBB). With focus on understanding BBB cell biology, receptor trafficking and key properties of an efficient transport vector

Genervon Biopharmaceuticals12:00 pm Bridging Luncheon Presentation: Disruptive and Novel Regulatory Therapeutic Strategy for Treatment of Neurodegenerative Diseases by Neuronal Peptide GM6

Winston_KoWinston Ko, CEO, Genervon Biopharmaceuticals, LLC

GM6 showed neuroprotection in neurodegenerative disease rodent models. Using DNA microarrays, Genervon identified 1259 genes altered ≥ 2-fold in SH-5YSY cells, including 89, 48, 46 and 9 genes associated with ALS, AD, PD and MS, respectively, suggesting repression of apoptotic pathway and stimulation of mitotic/proliferation pathways. Phase 1 and 2A trials demonstrated safety of GM6 and observed favorable shifts in biomarkers and improved functional measures. Planning Phase 3 trials.

12:30 Session Break

1:00 Coffee and Dessert in the Exhibit Hall with Poster Viewing

1:30 PLENARY KEYNOTE SESSION (click here for details)

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

4:15 Close of Conference


Event Categories
Keywords: Clinical , conference , Eating, industry , opportunities , opportunities, pharmaceutical , research , show, tools




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