Seventh Annual Parkinson's Disease Therapeutics Conference

Seventh Annual Parkinson's Disease Therapeutics Conference

Thursday, October 24, 2013

The New York Academy of Sciences

Presented By

Presented by The Michael J. Fox Foundation for Parkinson's Research and the New York Academy of Sciences

 

This event is sold out. Registration is closed. Onsite registration is not available for this conference.

The seventh annual Parkinson's Disease Therapeutics conference, chaired by C. Warren Olanow, MD, FRCPC, Mount Sinai School of Medicine, will highlight novel advances in basic and translational research that impact our understanding of Parkinson's Disease and its treatment. Select Michael J. Fox Foundation–funded investigators will present research on a variety of topics, including novel therapeutic targets, biomarkers for early detection and assessment of disease progression, and strategies to alleviate symptoms and/or to slow disease progression. In addition, a small poster session on innovative Parkinson's disease therapeutic targets and critical research tools will take place.

*Reception to follow.

Presented by

  • The Michael J. Fox Foundation for Parkinson's Research
  • The New York Academy of Sciences

Agenda

* Presentation titles and times are subject to change.


October 24, 2013

8:30 AM

Registration and Continental Breakfast

9:00 AM

Welcome
Kerstin Hofmeyer, PhD, The New York Academy of Sciences
Todd Sherer, PhD, The Michael J. Fox Foundation for Parkinson's Research
C. Warren Olanow, MD, FRCPC, Mount Sinai School of Medicine

9:20 AM

Disease Modifying Therapies

Results from a Sham-Surgery Controlled Phase 2b Trial Testing AAV2-Neurturin (CERE-120) in Moderately-Advanced Parkinson Disease: What Have We Learned and Where Do We Go from Here?
Raymond Bartus, PhD, RTBioconsultants, Inc.

Nonclinical Safety Studies of Selective LRRK2 Kinase Inhibitors
Reina Fuji, VMD, PhD, Genentech Inc.

Inosine for Parkinson's Disease: Safety and Trial Design Optimization
Michael A. Schwarzschild, MD, PhD, Massachusetts General Hospital

NPT001 Reduces Alpha-Synuclein Deposits and Improves Motor Performance in Alpha-Synuclein Overexpressing Mice
Kimberley S. Gannon, PhD, NeuroPhage Pharmaceuticals, Inc.

11:00 AM

Networking Break / Poster Viewing

11:30 AM

Symptomatic Therapies

Enhanced Activity in Rodent Models of Parkinsonism and L-DOPA-induced Dyskinesias by Preferential Targeting of Subpopulations of 5-HT1A Receptors
Adrian Newman-Tancredi, PhD, Neurolixis, Inc.

Development of a New Treatment for L-DOPA-induced Dyskinesias Targeting Opioid Receptors
Mary Maral Mouradian, MD, Rutgers - Robert Wood Johnson Medical School

DopaFuse: Development of a Continuously Infused, Subcutaneously Delivered Levodopa Prodrug for the Management of Parkinson's Disease
Ephraim Heller, SynAgile Corporation

12:45 PM

Lunch / Poster Viewing

1:45 PM

Research Tools and Resources

Salivary Gland Biopsies as a Diagnostic Test for Parkinson's Disease
Charles H. Adler, MD, PhD, Mayo Clinic Arizona / Arizona Parkinson's Disease Consortium

Validation of Biomarkers for Parkinson's Disease: the Critical Need for Robust Assays
Peggy Taylor, ScD, Covance Inc.

The Parkinson's Progression Markers Initiative — Developing Tools to Test Parkinson's Disease Therapeutics
Kenneth Marek, MD, Institute for Neurodegenerative Disorders

3:30 PM

Networking Break / Poster Viewing

4:00 PM

Hot Topics in Parkinson's Disease Research

Accelerating the Development of New Medicines to Patients through Drug Repositioning
Donald E. Frail, PhD, AstraZeneca PLC

What Have We Learned from Alzheimer's Disease Trials?
Eric Siemers, MD, Eli Lilly and Company

5:00 PM

Closing Remarks

5:15 PM

Cocktail Reception / Poster Viewing

7:00 PM

Conference Adjourns

Poster Presentations

LRRK2 Knockout Rat Characterization: Histopathology and Clinical Chemistry
Marco Baptista, PhD, The Michael J. Fox Foundation for Parkinson's Research

Non-Invasive Striatal Delivery of Glial Derived Neurotrophic Factor (GDNF) via a Novel Heterotopic Mucosal Grafting Technique
Benjamin S. Bleier, MD, Harvard Medical School / Massachusetts Eye and Ear Infirmary

A Feasibility Study to Evaluate Safety and Initial Effectiveness of MR Guided Focused Ultrasound for Unilateral Pallidotomy in the Treatment of Dyskinesia of Parkinson's Disease
Neal F. Kassell, MD, Focused Ultrasound Foundation / University of Virginia

Coordinated Reset (CR) Stimulation of the Subthalamic Nucleus in the MPTP Non-Human Primate Model: Target Validation for Translating into a Clinical Trial in Parkinson's Disease Patients
Wassilios Meissner, MD, PhD, CHU Bordeaux / Institut des Maladies Neurodégénératives, Université Bordeaux Ségalen

Accordion Pill Carbidopa — Levodopa (AP CD/LD) for Improved Treatment of Parkinson's Disease - 180 Days Oral Toxicity Study in Mini-Pigs, Towards Phase III Study
Nadav Navon, PhD, MBA, Intec Pharma Ltd.

Pharmacological Testing of Nurr1 Agonists in Animal Models of Parkinson's Disease
Thomas A. Rooney, PhD, Sanofi

mGluR3 PAM: a Novel Neuroprotective Strategy for Parkinson's Disease
Stephan Schann, PhD, Domain Therapeutics

Peripheral Administration of XPro1595, a Selective Inhibitor of Soluble TNF, in the Pre-clinical 6-OHDA Model of Parkinson's Disease
Malú G. Tansey, PhD, Emory University School of Medicine

MicroRNAs as Biomarkers for Parkinson's Disease; a Comparison of Cerebrospinal Fluid and Blood
Kendall Van Keuren-Jensen, PhD, Translational Genomics Research Institute

Role of LRRK2 in Alpha-Synuclein-Induced Neurodegeneration
Andrew West, PhD, University of Alabama at Birmingham

Speakers

Conference Chair

C. Warren Olanow, MD, FRCPC

Mount Sinai School of Medicine

C. Warren Olanow, MD, FRCPC is the Henry P. and Georgette Goldschmidt Professor and Chairman Emeritus of the Department of Neurology, and Professor in the Department of Neuroscience at the Mount Sinai School of Medicine in New York City. He is also Visiting Professor in the Department of Neurology at the University of California, San Francisco.

He received his medical degree from the University of Toronto, performed his neurology training at the New York Neurological Institute at Columbia Presbyterian Medical Center at Columbia University, and did post-graduate studies in neuroanatomy at Columbia University. He served on the faculties of McGill University, Duke University, and the University of South Florida prior to joining Mount Sinai.

He is past President of the Movement Disorder Society, past President of the International Society of Motor Disturbances, and past Treasurer of the American Neurological Association. He has been named an honorary Professor at the University of London (Royal Free Hospital), an honorary member of the French Neurological Society, an honorary Fellow of the Royal College of Physicians of the United Kingdom, the recipient of the Presidential Award from the Movement Disorder Society, and the 2013 recipient of the Movement Disorder Research Award from the American Academy of Neurology. He serves on the board of directors of the National Space Biomedical Research Institute, is a member of the executive committee of the Michael J. Fox Foundation Scientific Advisory Board, is the past Chairman of the scientific advisory board of the Bachmann-Strauss Foundation and has served on numerous additional medical and scientific advisory boards. He has served on several editorial boards, and is presently Co-Editor-in-Chief of the journal Movement Disorders.

His clinical and basic science research efforts are directed toward defining more effective therapies for Parkinson's disease and other neurodegenerative disorders. Dr. Olanow has authored more than 350 publications, and was ranked #1 in the United States in research citations for Parkinson's disease during the past quarter century. He has lectured on movement disorders at universities and conferences throughout the world.

Speakers

Charles H. Adler, MD, PhD

Mayo Clinic Arizona / Arizona Parkinson's Disease Consortium

Charles Adler received his bachelor's degree at Temple University (BA, Biology) and earned a master's degree and PhD in pharmacology, as well as his medical degree, from the New York University School of Medicine. He served his medical internship at New York University/Manhattan VA in New York and a neurology residency at the Hospital of the University of Pennsylvania and is board certified. Dr. Adler then completed a fellowship in movement disorders in the Department of Neurology at Graduate Hospital in Philadelphia. He joined the staff at Mayo Clinic in Scottsdale, Arizona where he is also a Consultant in the Department of Neurology.

Dr. Adler has received numerous grants to investigate experimental treatments for Parkinson's disease, essential tremor, dystonia, and restless legs syndrome from the National Institutes of Health, National Parkinson's Foundation, pharmaceutical companies, and Mayo Foundation for Medical Research. He currently is the Vice-Chair of the American Academy of Neurology Section of Movement Disorders, serves on the scientific advisory board of the Bachmann-Strauss Dystonia and Parkinson Foundation, is Co-Chair of the Parkinson Study Group Biomarkers Committee, and is the Co-Chair of the Movement Disorders Society Education Committee. Dr. Adler is a Fellow of the American Academy of Neurology and the American Neurological Association. He has previously served as the Vice-Chair of Research (Head of Human Subjects Research) at Mayo Clinic Scottsdale, has served on the editorial board of the journal Movement Disorders, executive committee of the American Academy of Neurology Section of Movement Disorders, multiple committees of the Parkinson Study Group, and was a member of the medical advisory board of the Restless Legs Syndrome Foundation.

He has a commitment to education: he is training residents, fellows (13), and graduate students; has given many invited lectures; and has developed multiple educational programs for the American Academy of Neurology, Movement Disorders Society, Mayo Clinic, and independent CME organizations.

Dr. Adler's main research interests are investigating which clinical tests may allow for an early diagnosis of Parkinson's disease and Parkinson's disease with dementia and identification of new treatments for Parkinson's disease and Parkinson's disease with dementia. He has published over 300 research papers and reviews, and edited a book entitled Parkinson's Disease and Movement Disorders: Diagnosis and Treatment Guidelines for the Practicing Physician. In addition to the studies of biomarkers in Parkinson's disease and dementia in Parkinson's disease, Dr. Adler has been funded to study movement abnormalities in patients with Parkinson's disease, treatment trials for both Parkinson's disease, dystonia, and restless legs syndrome, and he is investigating the yips: a possible focal task-specific dystonia of golfers.

Raymond Bartus, PhD

RTBioconsultants, Inc.

Dr. Bartus received a PhD in Neurosciences at North Carolina State University and has since focused his career on translational research and development (R&D) in industry, while also maintaining strong academic and scientific ties. He has participated in R&D of more than a dozen treatments that progressed into human clinical trials, involving a range of Central Nervous System (CNS) and non-CNS indications; nearly half have received US Food and Drug Administration (FDA) marketing approval. He has also published ~250 scientific papers and is listed by the Institute of Scientific Information (ISI) as a "Highly Cited Researcher," placing him in the top 0.5% of all scientists. He was the inaugural Editor-in-Chief for Neurobiology of Aging (for a decade) and has served on numerous elite panels, including for the FDA, United States Congress, the National Institutes of Health, and the United States Secretary of Health and Human Services.

Dr. Bartus' translational research and development experience extends 30+ years, gained during tenures at major multi-national pharmaceutical companies as well as smaller development-stage biotech companies. He has been at Ceregene since 2002, where he has strategic and overall operational responsibility for non-clinical, clinical, and regulatory activities involving all their neurotrophic/gene therapy programs for neurodegenerative diseases, including their multi-center, randomized Phase 2 clinical trials for Parkinson's (AAV2-neurturin or CERE-120) and Alzheimer's (AAV2-NGF or CERE-110) disease.

For the ten years prior to joining Ceregene, Dr. Bartus was Senior Vice President for Preclinical R&D at Alkermes, Inc. During this time the company grew from ~50 employees to well over 500 as he contributed to the development and regulatory filings of several products. During his tenure at Alkermes, he also conceived, championed, and led the pre-clinical development and initial clinical strategy for Vivitrol®, a once-a-month injectable treatment for alcoholism and opiate abuse (FDA approval was achieved in 2006), and the concept and early nonclinical development of pulmonary L-dopa (now the lead program at Alkermes-spin-off, Civitas Therapeutics, Inc). He is also recognized as one of the originators of the "Cholinergic Hypothesis," providing major aspects of the nonclinical translational R&D which led to the first four drugs approved by the FDA for Alzheimer's disease.

Donald E. Frail, PhD

AstraZeneca PLC

Dr. Frail leads the science group in the New Opportunities iMed, which seeks new opportunities complementary to AstraZeneca core areas through drug repositioning and open innovation partnerships. Recently, the team implemented groundbreaking partnerships with the Medical Research Council UK and National Institutes of Health to collaborate with investigators to explore the use of AstraZeneca development compounds in new indications. Dr. Frail recently co-authored the book "Drug Repositioning: Bringing New Life to Shelved Assets and Existing Drugs". Prior to joining AstraZeneca last year, Dr. Frail held several leadership positions, including founder and Chief Scientific Officer of the Indications Discovery Unit at Pfizer, Head of Pfizer's St. Louis Research & Development site, Vice President of Biology for the St. Louis site, and Head of Discovery Neurosciences at Pharmacia.

Reina Fuji, VMD, PhD

Genentech Inc.

Dr. Reina Fuji is a Senior Scientist–Pathologist in the Safety Assessment department at Genentech. She provides pathology support for the nonclinical safety evaluation of drug candidates in Research and Development and guides drug development strategies for a variety of biologic and small molecule neurobiology, immunology, and oncology programs. Dr. Fuji received her Veterinary Medical degree from the University of Pennsylvania, PhD in Pharmacology and Biochemistry from Cornell University, and is a Diplomate of the American College of Veterinary Pathologists.

Kimberley S. Gannon, PhD

NeuroPhage Pharmaceuticals, Inc.

Dr. Gannon received a PhD in neuroscience from The Florida State University in 1994 and conducted her post-doctoral training at Hoffmann-La Roche in the Institute of Molecular Biology and Mount Sinai School of Medicine in the department of physiology and biophysics. Although experienced in all aspects of drug development, her main areas of expertise are preclinical efficacy and translational research. She has worked extensively in the pharmaceutical industry, holding positions at SmithKline Beecham, Eli Lilly, and EPIX Pharmaceuticals. Dr. Gannon joined NeuroPhage in October 2009 and oversees preclinical Research & Development. Her main focus is currently on the development of NPT001 for neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

Ephraim Heller

SynAgile Corporation

Ephraim Heller is the Founding Chief Executive Officer of SynAgile. Mr. Heller was previously Founding Chief Executive Officer of AngioScore Inc., a privately held balloon angioplasty company with 2012 revenues of $50 million. Before that, he was Founding Chief Executive Officer and later Vice President of Marketing and Vice President of Business Development at TheraSense Inc., a maker of blood glucose monitoring systems for people with diabetes. TheraSense Inc. went public in 2001, sales grew to $270 million in 2003, and the company was acquired by Abbott for $1.2 billion in 2004. Mr. Heller holds over 90 issued US patents. He received a BA in Physics from Harvard and an MBA from Yale.

Kenneth Marek, MD

Institute for Neurodegenerative Disorders

Kenneth Marek is President and Senior Scientist at the Institute for Neurodegenerative Disorders. He received his medical degree from Yale University and was trained in internal medicine and neurology at the Johns Hopkins School of Medicine. He has been a faculty member in the Departments of Neurology at Johns Hopkins University and Yale University. Dr. Marek has been the recipient of numerous grants and awards including those from the National Institutes of Health, Department of Defense, Parkinson's Disease Foundation, and National Parkinson's Foundation, and The Michael J. Fox Foundation.

Dr. Marek's major research interests include identification of biomarkers for early detection, assessment of disease progression, and development of new treatments for Parkinson's disease, Alzheimer's disease, and related neurodegenerative disorders. His specific interest has been in in vivo neuroreceptor imaging biomarkers. He has authored numerous neurology and neuroscience publications on these topics. Dr. Marek has been and continues to be the principal investigator of several ongoing multi-center international studies (including the Parkinson's Progression Markers Initiative [PPMI] and the Parkinson's Associated Risk Syndrome [PARS] study) investigating the use of biomarkers to assess the onset, progression, and effect of treatment in Parkinson's disease, Alzheimer's disease, and other neurodegenerative diseases.

Dr. Marek serves on the scientific advisory board of The Michael J. Fox Foundation. He has served on the executive committee of the Parkinson's Study Group and in leadership roles in the Huntington Study Group. He also was a Co-Founder and continues to lead Molecular NeuroImaging, LLC, a company providing clinical neuroimaging research services.

Mary Maral Mouradian, MD

Rutgers - Robert Wood Johnson Medical School

Dr. Mouradian is the William Dow Lovett Professor of Neurology, and Director, Center for Neurodegenerative and Neuroimmunologic Diseases at the Rutgers - Robert Wood Johnson Medical School. She received her MD with distinction from the American University of Beirut, and obtained neurology residency training at the University of Cincinnati. She then joined the National Institutes of Health (NIH) where she received further training in clinical neuropharmacology at the National Institute of Neurological Disorders and Stroke (NINDS), and in molecular biology under the tutelage of the Nobel Laureate Marshall Nirenberg at the National Heart, Lung, and Blood Institute. Between 1990 and 2003, Dr. Mouradian directed the Genetic Pharmacology Unit of NINDS before assuming her current posts. Her contributions to Parkinson's disease research span the description of key pharmacodynamic alterations indicative of the brain's plasticity in response to pulsatile levodopa therapy, to the identification of molecular pathogenetic mechanisms of neurodegeneration. Dr. Mouradian is an elected member of the Alpha Omega Alpha Honor Medical Society and a Fellow of the American Neurological Association and the American Academy of Neurology. She is an Associate Editor of the journal Pharmacology and Therapeutics, serves on the editorial boards of several other scientific journals, and is a member of the scientific advisory board of the American Parkinson Disease Association (APDA). To date, she has authored over 195 scholarly publications. Her research is funded by the NIH, the Michael J. Fox Foundation for Parkinson's Research, and industry. Among her honors are the Roger Duvoisin Research Scholar Award from the APDA, the Excellence in Research Award from the New Jersey Health Foundation, and the NIH Award of Merit.

Adrian Newman-Tancredi, PhD

Neurolixis, Inc.

Dr. Adrian Newman-Tancredi has over 20 years experience of neuroscience research and drug discovery. Prior to joining Neurolixis, he was Director of Neurobiology and Project Manager at Pierre Fabre Laboratories where he led multi-disciplinary programs that successfully identified and characterized novel antipsychotics, antidepressants, and analgesics. Prior to Pierre Fabre, Dr. Newman-Tancredi led a molecular pharmacology research group at the Servier Research Institute where he was responsible for screening of new chemical entities (NCEs) and investigating signal transduction mechanisms of monoamine receptors. Dr. Newman-Tancredi has extensive experience of project management, integrating medicinal chemistry, pharmacology, early ADMET and pre-clinical development, and building international collaborations with academic researchers. Dr. Newman-Tancredi has published over 130 research reports, co-authored patents on NCEs, and given presentations to a wide variety of audiences. He serves on the editorial board of theInternational Journal of Neuropsychopharmacology and as an independent neuropharmacology and drug discovery consultant. Dr. Newman-Tancredi received his BSc with honors in biochemistry and his PhD in neuropharmacology from the University of Kent at Canterbury, UK.

Michael A. Schwarzschild, MD, PhD

Massachusetts General Hospital

After obtaining his undergraduate training in biochemistry at Princeton University, Dr. Schwarzschild went on to medical and graduate neuroscience training at Harvard Medical School. There he pursued his PhD thesis with Dr. Richard Zigmond on the neurochemistry of tyrosine hydroxylase, the enzyme controlling dopamine biosynthesis. He undertook neurology residency and then Parkinson's disease fellowship training at Massachusetts General Hospital (MGH) under the guidance of Drs. Anne Young and John Growdon. During a postdoctoral research fellowship with Dr. Steve Hyman in the mid-90s, he developed expertise in gene regulation and cell death pathways in the dopamine-rich brain region most affected in Parkinson's disease.

Since 1996, Dr. Schwarzschild has directed the Molecular Neurobiology Laboratory at MGH, focusing on the role of three purines—adenosine, caffeine and urate—in animal models of Parkinson's disease. Together with Dr. Jiang-Fan Chen he discovered the neuroprotective properties of adenosine A2A receptor blockers (including caffeine) in mouse models of the disease. His research team then provided evidence that these drugs may help prevent dyskinesia, a side effect of standard anti-parkinsonian therapy. His leadership of a series of international research conferences on A2A receptors in Parkinson's has helped translate our understanding of this drug target into an exciting new therapy for Parkinson's patients.

Most recently, through a fruitful interdisciplinary collaboration with epidemiologist Dr. Alberto Ascherio of the Harvard School of Public Health, Dr. Schwarzschild and his colleagues have discovered an unprecedented clue to why disease progression is mild in some and aggressive in others. In partnership with the Parkinson Study Group (PSG) they showed that the purine antioxidant urate can serve as a predictor of not only the risk of PD, but also the rate at which it progresses. Their work identifies urate as a molecular biomarker of Parkinson's disease progression rate and as a candidate neuroprotective agent too.

Dr. Schwarzschild has been the recipient of a George C. Cotzias Fellowship from the American Parkinson's Disease Association and a Paul Beeson Physician Faculty Scholar Award for Aging Research. Since 1997, he has been an active clinical investigator in disease progression trials of the PSG. He is currently an Associate Professor of Neurology at Harvard Medical School and a staff physician on the Neurology Service at MGH where he works with Parkinson's patients and their families in his weekly movement disorders clinic.

Eric Siemers, MD

Eli Lilly and Company

Eric Siemers, MD is the Senior Medical Director of the Alzheimer's Disease Team in the Biomedicines Business Unit. He earned his MD with highest distinction from the Indiana University School of Medicine in 1982. After an internship in the Department of Internal Medicine at the Indiana University School of Medicine, he completed his residency in the Department of Neurology in 1986. Prior to joining Lilly, he founded and headed the Indiana University Movement Disorder Clinic; his previous research included investigations of Parkinson's disease and Huntington's disease, and he established one of the first centers for surgical Parkinson's disease treatments in the US. Dr. Siemers currently directs late stage clinical research efforts at Lilly concerning investigational treatments for Alzheimer's disease, and is more broadly involved with other neurological indications such as Parkinson's disease. Major research interests include the use of biomarkers in investigational drug research and the development of trial designs that broadly characterize the effects of investigational drugs on chronic diseases. Dr. Siemers is a founding member of the Alzheimer's Association Research Roundtable and is currently serving as Co-chair. He is a member of the Steering Committee for the Alzheimer's Disease Neuroimaging Initiative (ADNI), which is funded by the National Institute on Aging (NIA) and a consortium of pharmaceutical companies. He served as the chair of the Industry Scientific Advisory Board for ADNI in 2007 and previously served as a member of the Resource Allocation Request Committee. He participated as a member of the NIA working group that proposed criteria for preclinical Alzheimer's disease in 2011. He is a past member of the Board of Directors of the American Society of Experimental Neurotherapeutics.

Peggy Taylor, ScD

Covance Inc.

Dr. Taylor is currently the Director of the Antibody Products group at Covance where she is responsible for scientific and operational leadership of the business. Prior to joining Covance she was Vice President of Production and Development at Signet Laboratories in Dedham, MA. Dr. Taylor previously held the role of Vice President of Research at Sequitur, Inc., where she gained substantial experience in the use of antisense and RNA interference technologies as research tools. Peggy earned a Doctor of Science degree in cell biology from Harvard University and is a member of the New York Academy of Science and the American Association for the Advancement of Science.

Travel & Lodging

Our Location

The New York Academy of Sciences

7 World Trade Center
250 Greenwich Street, 40th floor
New York, NY 10007-2157
212.298.8600

Directions to the Academy

Hotels

A small number of rooms have been blocked for conference participants at the Cosmopolitan Hotel — Tribeca.

All room rates and reservations are subject to availability.

Cosmopolitan Hotel — Tribeca
95 West Broadway
New York, NY 10007

Call 1-888-895-9400 or email reservations@cosmohotel.com or cosmores@triumphny.com. Please identify yourself as being with the Michael J. Fox Foundation for Parkinson’s Research — October Group. You may choose a room for one night (Wednesday, October 23 only) or two (Wednesday and Thursday, October 23 and 24). If desired, ask for a "quiet room."

Availability: 30 rooms for Wednesday, October 23, 2013, and 20 rooms for Thursday, October 24, 2013

Deadline to book: Monday, September 23, 2013