Science 1st - Neuroscience: Challenging the Status Quo on Apolipoprotein E Drug Discovery for Alzheimer’s Disease

Oct 19 2015

JLABS EVENT On Monday, during the Society for Neuroscience Conference in Chicago IL, join Johnson & Johnson Innovation as we explore the challenges hindering development of therapeutic drugs targeting Apolipoprotein E (ApoE), the major genetic risk factor for non-familial Alzheimer's disease (AD).

Problem statement:
The e4 allele in Apolipoprotein E is the major genetic risk factor for sporadic or late-onset Alzheimer's disease. Despite intense research in the field since its discovery over two decades ago (Strittmatter et al., Proc Natl Acad Sci U S A. 90(5):1977-81, 1993) no agents that target the biology of ApoE4 have been successfully developed as therapeutic treatments for AD. Why? In part this may be due to the complex and different roles of Apolipoprotein E in the brain and body. Emerging evidence also indicates that ApoE4 may play a role not just by increasing the risk of Alzheimer's disease but may play a role in the rate of functional decline.

The goal of this event will be to explore those features in detail and to challenge the dogma that has hindered the development of therapeutic agents in this area. Invited speakers and panelists will discuss:

  • The role the e4 allele plays in the genetics of neurodegenerative disease,
  • The latest findings on the functional biochemical consequences of ApoE4,
  • The diversity & prioritization of novel ApoE4 drug discovery targets,
  • And the potential challenges in translation of ApoE4 based therapeutics to the clinical setting.

4:00pm | Registration Opens
4:30pm | Presentations
                 1. Setting the stage on the role of ApoE4 in Alzheimer's disease
                 2. Functional & biochemical consequences of e4 mutation
                 3. Diversity & prioritization of novel e4 related drug discovery targets
                 4. Targeting ApoE4-containing lipoproteins in the CNS:
                     Repurposing drugs form the cardiovascular field
6:10pm | Panel discussion
7:00pm | Networking Reception
8:30pm | Close

Kelly Bales | Head of Neurodegeneration & Neurological Disease, Pfizer read bio»
Guojun Bu | Professor and Associate Director, Mayo Clinic ADRC, Dept. of Neuroscience, Mayo Clinic read bio»
David Holtzman | Professor and Chairman, Dept. of Neurology, Washington University School of Medicine read bio»
Mary Jo LaDu | Professor, Dept. of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago read bio»
Steven Paul | President & CEO, Voyager Therapeutics read bio»
Cheryl Wellington | Dept. of Pathology and Laboratory Medicine, University of British Columbia read bio»
[moderator] Guy Seabrook | Vice President, Neuroscience Innovation, Johnson & Johnson Innovation read bio»

Who Should Attend:
Neuroscience leaders, including founders, CEOs, and other executives of start-ups and private companies.

Free event.

Alzheimer's Association Partners:
This event is presented in partnership with the Alzheimer's Association.

MATTER 222 Merchandise Mart Plaza
Suite 1230
Chicago, IL 60654

About the Science First series:
The purpose of the Science First series, sponsored by Johnson & Johnson Innovation, JLABS, is to bring together top experts to explore a pressing topic in their scientific field. It is a chance for local scientists, researchers, and entrepreneurs to present and dialogue on new discoveries, advancing techniques, and other cutting-edge science themes.

Participants' Biographies:
Kelly Bales Kelly R. Bales, Ph.D. | Vice President, Neuroscience & Pain Research Unit, Head of Degeneration, Inflammation & Vascular Biology, and Pfizer Neuroscience Investigator, Pfizer, Inc.
Kelly Bales is Vice President, Head of the Degeneration, Inflammation & Vascular Biology group and a Pfizer Neuroscience Investigator within the Neuroscience & Pain Research Unit that is located in Cambridge, MA. Since joining Pfizer, Kelly has built a group focused mechanisms and targets implicated in the pathophysiology of neurodegenerative diseases. She has lead several projects from mechanism identification to "first in human studies" and has more than 20 years' experience in the pharmaceutical industry. Additionally, Kelly and her laboratory have made seminal contributions investigating the interaction between apolipoprotein E and -amyloid. Kelly is recognized internationally as an expert in the area of pre-clinical animal models of Alzheimer's disease, has co-authored more than 90 peer-reviewed publications, numerous review articles and invited book chapters. She is also co-inventor on numerous patents related to novel therapies for AD.

Guojun Bu Guojun Bu, Ph.D. | Professor and Associate Director, Mayo Clinic ADRC, Dept. of Neuroscience, Mayo Clinic
Dr. Bu is a Professor of Neuroscience at the Mayo Clinic Jacksonville. His primary research interest is to understand why ApoE4 is a strong risk factor for Alzheimer's disease and how this pathway can be targeted for therapy. He is a leader in the field of research related to the low-density lipoprotein receptor family with LRP1 serving as a major receptor for both APOE and Abeta in the brain. His scientific contributions have garnered numerous awards, including the Zenith Fellows Award from the Alzheimer's Association and the Established Investigator Award from the American Heart Association. Dr. Bu serves as the Editor-in-Chief for Molecular Neurodegeneration and is also an Associate Director of the Alzheimer's Disease Research Center at the Mayo Clinic.

David Holtzman David Holtzman | Professor and Chairman, Dept. of Neurology, Washington University School of Medicine
David M. Holtzman received his BS and MD from Northwestern University followed by medical internship and Neurology residency training at UCSF. His did his post-doctoral training at UCSF in the lab of William Mobley. He moved to Washington University in 1994 where he is currently the Andrew B. and Gretchen C. Jones Professor and Chairman of Neurology since 2003. He also is the scientific director of the Hope Center for Neurological Disorders and Associate Director of the Knight ADRC. His laboratory has focused its studies on the role of ApoE, Aβ, and tau metabolism in the pathogenesis and potential treatment of Alzheimer's disease. He has received several awards and honors for his work including the MetLife Award, the Potamkin prize, and being elected to that National Academy of Medicine.

Mary Jo LaDu Mary Jo LaDu, Ph.D. | Professor, Dept. of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago
My lab focuses on the role of apoE-containing lipoproteins in the CNS, specifically their role in Abeta42 (AB42) clearance. Our tale of 2 proteins began with trying to understand the protein:protein interactions between a lipid-associated protein/lipoprotein and a peptide with multiple aggregation states that are difficult to manage, continued through primary cell cultures and is now centered on EFAD transgenic mice, mice that express the human apoE isoforms and over-expresses AB42. In spite of studying 2 of the most mis-behaved proteins, our goal remains identifying a therapeutic target that corrects the relative instability of ApoE4-containing CNS lipoproteins, including increasing its lipidation state, thus reducing soluble, oligomeric AB42.
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Steven Paul Steven Paul, M.D. | President & CEO, Voyager Therapeutics
Steven M. Paul, M.D., is currently the President and CEO at Voyager Therapeutics, Inc. as well as Venture Partner at Third Rock Ventures. He was formerly the Founding Director of the Helen and Robert Appel Alzheimer's Disease Research Institute and the Burton P. and Judith B. Resnick Distinguished Professor in Neurodegenerative Diseases as well as a DeWitt Senior Scholar and Professor of Neuroscience (Brain and Mind Research Institute), Psychiatry and Pharmacology at Weill Cornell Medical College. Dr. Paul was also formerly the Executive Vice President of Science and Technology and President of the Lilly Research Laboratories (LRL) of Eli Lilly and Company, overseeing the development of several of Lilly's largest products including Zyprexa® and Cymbalta®. Prior to assuming his position at Lilly and Weill Cornell Medical College, Dr. Paul served as Scientific Director of the National Institute of Mental Health (NIMH/NIH) in Bethesda, Maryland. Dr. Paul is a member of various professional and honorary societies, including Phi Eta Sigma; Alpha Epsilon Delta; Sigma Xi; Phi Beta Kappa; and the Alpha Omega Alpha Honorary Medical Society. He is the recipient of many honors and scientific recognitions, including: The Distinguished Service Medal of the USPHS and the Chief Scientific Officer of the Year Award. In 1997, Dr. Paul was elected to membership in the National Academy of Medicine of the National Academy of Sciences and in 2004 Dr. Paul was elected a Fellow of the American Association for the Advancement of Science (AAAS). Dr. Paul has authored or co-authored over 500 papers and invited book chapters and was listed as one of the most highly cited scientists in the world (top 50 in Neuroscience) (1980-2000) by the Institute for Scientific Information (I.S.I.), Philadelphia, Pennsylvania. He holds 9 patents on inventions made both at NIH and Lilly. His current work has focused on the role of apoE in the pathogenesis of Alzheimer's disease. He is also an co-inventor of solanezumab, a humanized anti-Aβ monoclonal antibody currently in late-stage clinical testing by Lilly as a potential disease-modifying treatment for Alzheimer's disease. Dr. Paul is on the boards of several publicly traded and private biopharmaceutical companies including Alnylam Pharmaceuticals, SAGE Therapeutics and the Sigma Aldrich Company and is also a founder of Sage Therapeutics, Voyager Therapeutics, and Tal Medical, dedicated to discovering and developing novel therapeutics for neurological and psychiatric disorders.

Cheryl Wellington Cheryl Wellington, Ph.D. | Prfessor, Dept. of Pathology and Laboratory Medicine, University of British Columbia
Dr. Wellington obtained her Ph.D. at the University of British Columbia in 1991 and did postdoctoral training at Harvard Medical School, the University of Calgary, and the University of British Columbia. She joined the Department of Pathology and Laboratory Medicine at the University of British Columbia in 2000. Dr. Wellington's research interests focus on both genetic and environmental risk factors for dementia, including apolipoprotein E (apoE) metabolism, history of traumatic brain injury (TBI), and cerebrovascular dysfunction. Current research projects include drug discovery efforts to increase apolipoprotein function in the brain for application to both Alzheimer's Disease and TBI, understanding the relationships between TBI and dementia, tissue engineering approaches to investigate cerebrovascular function in health and disease.
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Guy Seabrook [moderator] Guy Seabrook, Ph.D. | Vice President, Neuroscience Innovation, Johnson & Johnson Innovation
Guy is Vice President of Neuroscience Scientific Innovation at Johnson & Johnson Innovation, California. Guy has more than 23 years of drug discovery research experience, which includes preclinical research on marketed products and candidates in clinical development. Formerly, Guy was part of Eli Lilly's Global External Research & Development organization where he led the the Lilly Bio-Medicines Business Unit, and also at Merck & Co, Inc where he was the Head of the West Point Department of Alzheimer's Disease Research. Guy graduated with a PhD in Zoology from the University of Nottingham UK, and completed his postdoctoral research at the University of Miami School of Medicine USA.
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