2012 Michael, Marcia, and Christa Parseghian
Scientific Conference for
Niemann-Pick Type C Research
June 7-9th, 2012
THURSDAY, JUNE 7
11:00 a.m. –noon
Registration
Jordan Hall Galleria
Noon-1:15 p.m.
LUNCH
Jordan Hall Galleria
Jordan Hall of Science, Room 105
1:15 – 1:25 p.m.
Opening Remarks
Richard E. Taylor, Associate Dean for Research, College of Science
1:25 – 1:30 p.m.
Deidre Davis, Senior Vice President, Notre Dame Federal Credit Union
1:30 – 2:15 p.m.
Keynote Lecture. Unfinished journey: Niemann-Pick disease, type C in its seventh
decade
Marc Patterson
Mayo Clinic Children’s Center
[Abstract # 1, p. 8]
SESSION I: Molecular and Cellular Biology
Jordan Hall of Science, Room 105
Chair: Holly Goodson, Department of Chemistry and Biochemistry, University of Notre Dame
2:15 – 2:45 p.m.
Cholesterol export from lysosomes by NPC1 and NPC2 proteins
Maika Deffieu and Suzanne R. Pfeffer
Stanford University School of Medicine
[Abstract # 2, p. 9]
2:45 – 3:15 p.m.
Identification of novel regulators of endosomal cholesterol trafficking
Ximing Du, Abdulla Kazim, Andrew J. Brown, and Hongyuan Yang
School of Biotechnology and Biomolecular Sciences, University of New South Wales
[Abstract # 3, p. 10]
3:15 – 3:45 p.m.
COFFEE BREAK
Jordan Hall Galleria
3:45 – 3:50 p.m.
Brief Greeting from Gregory Crawford, Dean, College of Science
3:50 – 4:20 p.m.
Ryanodine receptor antagonists adapt NPC1 proteostasis to ameliorate lipid storage in
Niemann-Pick type C disease fibroblasts
Ting Yu, Chan Chung, Dongbiao Shen, Haoxing Xu, and Andrew P. Lieberman
University of Michigan Medical School
[Abstract # 4, p. 11]
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4:20 – 4:50 p.m.
Use of induced pluripotent stem cells to model selective neuronal failure in NiemannPick type C1
M. Paulina Ordonez and Lawrence S.B. Goldstein
University of California San Diego
[Abstract # 5, p. 12]
4:50 – 5:20 p.m.
In vitro modeling of inherited neurodegenerative cholesterol storage disorder using
patient-specific induced pluripotent stem cells (hiPSCs)
Dorothea Maetzel1, Haoyi Wang1, Lina Abi Mosleh2, Qing Gao1, Maisam Mitalipova1,
Rudolf Jaenisch1
1Whitehead Institute for Biomedical Research, Cambridge, MA
2UT Southwestern Medical Center
[Abstract # 6, p. 13]
5:20 – 6:30 p.m.
POSTER SESSION and COCKTAIL HOUR (cash bar)
Jordan Hall Galleria
6:30 – 7:45 p.m.
DINNER
Jordan Hall Galleria
8:00 p.m.
Informal Discussions: Researchers
Leahy’s at the Morris Inn
Informal Discussions: Parents and Patient Advocates (cash bar)
Jordan Hall Reading Room
FRIDAY, JUNE 8
SESSION II: Developing Diagnostics
Jordan Hall of Science, Room 105
Chair: Basar Bilgiçer, Department of Chemical and Biomolecular Engineering, University of Notre Dame
8:00 – 8:30 a.m.
NPC-509: Establishment of a novel biomarker for the primary diagnosis and monitoring
of Niemann-Pick Type C disease
Anne-Katrin Giese1, Ulrike Grittner2, Hermann Mascher3, Arndt Rolfs1
1Albrecht-Kossel-Institute for Neuroregeneration, University of
Rostock, Germany
2Institute for Biostatistics and Clinical Epidemiology, Charité-University Medicine, Germany
3pharm--analyt Labor GmbH, Baden, Austria
[Abstract # 7, p. 14]
8:30 – 9:00 a.m.
Oxysterol biomarkers for Niemann-Pick C1 disease
Xuntian Jiang1, Rohini Sidhu1, Martin Fan1, Hideji Fujiwara1, Jessie Zhang1, Hui
Jiang1, David E. Scherrer1, Nicole M. Yanjanin2, Forbes D. Porter2, Cristin Davidson3,
Steven U. Walkley3, Charles Vite4, Jean E. Schaffer1, and Daniel S. Ory1
1Washington University School of Medicine, St. Louis
2PDGEN, NICHD, NIH, DHHS;
3Albert Einstein College of Medicine
4University of Pennsylvania
[Abstract # 8, p. 15]
2
9:00 – 9:30 a.m.
Correlates of innate immunity and disease therapies in a murine model of Niemann-Pick
Type C Disease
Md. Suhail Alam1, Michelle Getz1, Mary Cloutier1, Sue Yi1, Jenny Shin1, Martha
McGraw1, Dan Grace1, Michael Kress1, Stephanie Maciuba1, Annie Oesterling1, Sun
Hee Park1, Michelle Yanik1, Peter Velazquez1,2 and Kasturi Haldar1
1Center for Rare and Neglected Diseases, University of Notre Dame
2Indiana University School of Medicine – South Bend
[Abstract # 9, p. 16]
9:30 – 10:00 a.m.
COFFEE BREAK
Jordan Hall Galleria
SESSION III: Approaching New Treatments in Patients
Jordan Hall of Science, Room 105
Chair: Matthew Scott, Stanford School of Medicine
10:00 – 10:30 a.m.
Patient Perspectives: Michael and Sabine Fornfeist
10:30 – 11:00 a.m.
Development of a hydroxypropyl-β-cyclodextrin therapeutic trial for Niemann-Pick
disease, type C1
Forbes D. Porter1 and the TRND Team2
1Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS
2Team coordinated by Therapeutics for Rare and Neglected Diseases Program, NCATS, NIH,
DHHS
[Abstract # 10, p. 17]
11:00 – 11:30 a.m.
Use of cyclodextrin in two Brazilian girls with Niemann-Pick Type C – intrathecal report
Camilo Vieira and Rita Lucena
Child Neurology Department, Federal University of Bahia
[Abstract # 11, p. 18]
11:30 – 12:00 p.m.
The repurposing of vorinostat for the treatment of Niemann-Pick Type C
Norbert Wiech
Lysomics, LLC
[Abstract # 12, p. 19]
12:00 – 12:30 p.m.
Psychology and psychiatry: needs and fears of individuals with Niemann-Pick Type C
(NP-C)
Hans-H. Kluenemann and Lisa Peintinger
Clinic and Policlinic for Psychiatry and Psychotherapy, Regensburg, Germany
[Abstract # 13, p. 20]
12:30 – 1:30 p.m.
LUNCH
Jordan Hall of Science Galleria
SESSION IV: From Molecules to Drugs
Jordan Hall of Science, Room 105
Chair: Joyce Repa, UT Southwestern Medical Center
3
1:30 – 2:00 p.m.
Global impact of proteostasis regulation on Niemann-Pick C1 (NPC1) disease
Kanagaraj Subramanian and William E. Balch
The Scripps Research Institute, Department of Cell Biology, Chemical Physiology, The Skaggs
Institute of Chemical Biology, and The Institute of Childhood and Neglected Diseases
[Abstract # 14, p. 21]
2:00 – 2:30 p.m.
Testing the effect of drugs on arrays of NPC1 mutations
Shu Mao1, Nina Pipalia1, Kanagaraj Subramanian2, William Balch2 and Fred
Maxfield1
1Department of Biochemistry, Weill Cornell Medical College, Cornell University
2Department of Cell Biology, Chemical Physiology, The Scripps Research Institute
[Abstract # 15, p. 22]
2:30 – 3:00 p.m.
Testing histone deacetylase inhibitors as NPC therapeutics
Frederick R. Maxfield
Weill Cornell Medical College, Cornell University
[Abstract # 16, p. 23]
3:00 – 3:30 p.m.
Translation of disease modifiers from yeast to mouse models of Niemann-Pick type C
disease
Andrew Munkacsi1, Remy T. Schneider1, Lauren S. Csaki2, Xuntian Jiang3, Rohini
Sidhu3, Karen Reue2, Daniel S. Ory3, Robert A. Maue4 and Stephen L. Sturley5
1Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University
Medical Center
2Department of Human Genetics, David Geffen School of Medicine, University of California
3Diabetic Cardiovascular Disease Center, Washington University School of Medicine
4Department of Physiology & Neurobiology, Dartmouth Medical School
5Department of Pediatrics and Institute of Human Nutrition, Columbia University Medical
Center
[Abstract # 17, p. 24]
3:30 – 4:00 p.m.
COFFEE BREAK
Jordan Hall Galleria
4:00 – 4:15 p.m.
Regulation of cholesterol homeostasis with spliceosome inhibitor herboxidiene, a
potentially novel lead for Niemann-Pick Type C disease
Zachary Wehrmann, Jarred Pickering, D. Cole Stevens, Holly Goodson and Richard
Taylor
Department of Chemistry and Biochemistry, University of Notre Dame
[Abstract # 18, p. 25]
4:15 – 4:30 p.m.
Quantitative analysis of the effects of various drugs on cholesterol levels in NPC
fibroblasts
Zachary Wehrmann, Tyler Hulett, Kara Huegel, Kevin Vaughan, Olaf Wiest, Paul
Helquist and Holly Goodson
Department of Chemistry and Biochemistry, University of Notre Dame
[Abstract # 19, p. 26]
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SESSION V: Cyclodextrin – Drug Development and Molecular Basis, Part I.
Chair: Forbes D. Porter, National Institutes of Health
4:30 – 5:00 p.m.
Molecular mechanism of β-cyclodextrin mediated cholesterol extraction from
biomembranes: the key to understanding its palliative effect in Niemann-Pick type C
disease
Cesar Lopez, Alex H. de Vries, Siewert-Jan Marrink
Groningen Biomolecular Sciences and Biotechnology Institute & Zernike Institute for Advanced
Materials, University of Groningen, The Netherlands
[Abstract # 20, p. 27]
5:00 – 5:30 p.m.
Efficacy of different cyclodextrins in the treatment of Niemann-Pick type C disease
Cristin D. Davidson1, Nafeeza F. Ali1, Marie T. Vanier2, Kostantin Dobrenis1 and
Steven U. Walkley1
1Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center, Albert Einstein
College of Medicine
2Institut National de la Sante et de la Recherche Medicale, Laennec Medical School and Lyon-1
University, France
[Abstract # 21, p. 28]
5:30 – 6:00 p.m.
Cholesterol transport by NPC2 and the therapeutic use of cyclodextrin polymers in NPC
cells
Leslie McCauliff and Judith Storch
Department of Nutritional Sciences and Rutgers Center for Lipid Research, Rutgers University
[Abstract # 22, p. 29]
6:00 – 7:00 p.m.
POSTER SESSION and COCKTAIL HOUR (cash bar)
Pressbox, ND Stadium
7:00 – 9:00 p.m.
DINNER
Pressbox, ND Stadium
SATURDAY, JUNE 9
SESSION V: Cyclodextrin, Part II
Jordan Hall of Science, Room 105
Chair: Judith Storch, Rutgers University
8:00 – 8:30 a.m.
Combining cyclodextrin and LXR agonist therapies as treatment for
Niemann-Pick Type C disease
Anna M. Taylor, Yelenis Mari, and Joyce J. Repa
UT Southwestern Medical Center
[Abstract # 23, p. 30]
8:30 – 9:00 a.m.
Comparing the molecular mechanisms of novel therapies for NP-C disease
Anna Taylor1, Yelenis Mari1, Olaf Wiest2, Paul Helquist2, and Joyce J. Repa1
1UT Southwestern Medical Center
2Department of Chemistry and Biochemistry, University of Notre Dame
[Abstract # 24, p. 31]
5
9:00 – 9:30 a.m.
Synthesis and characterization of non-covalent β-cyclodextrin polymer derivatives for
evaluation as potential NPC therapeutics
Christopher J. Collins, Yawo Mondijou and David H. Thompson
Department of Chemistry, Purdue University
[Abstract # 25, p. 32]
9:30 – 10:00 a.m.
Normalization of cholesterol homeostasis by 2-hydroxypropyl- β -cyclodextrin in
neurons and glia from Niemann-Pick C1-deficient mice
Kyle B. Peake and Jean E. Vance
Group on Molecular and Cell Biology of Lipids and Department of Medicine
University of Alberta
[Abstract # 26, p. 33]
10:00 – 10:30 a.m.
COFFEE BREAK
SESSION VI: Pathological Models of NP-C
Jordan Hall of Science, Room 105
Chair: Daniel Ory, Washington University in St. Louis, School of Medicine
10:30 – 11:00 a.m.
Intrathecal cyclodextrin ameliorates neurological dysfunction and improves Purkinje
cell survival in presymptomatic and postsymptomatic cats with Niemann-Pick Disease
Type C
Charles H. Vite1, Veronika M. Stein1,2, Elizabeth Mauldin1, Jessica Bagel1, Maria
Prociuk1, Patricia O’Donnell1,Tracey Sikora1, Therese Ruane1, Alexandra Crooks1,
Sarah Ward1, Mark Kao3, John deGroot4, Daniel Ory5, Marie T. Vanier6, Steven U.
Walkley7
1School of Veterinary Medicine, University of Pennsylvania
2Stiftung Tieraerztliche Hochschule Hannover, Germany
3Johnson & Johnson Pharmaceutical Research & Development, LLC
4University Medical Center Utrecht
5Washington University, St. Louis
6Institut National de la Santé et de la Recherche Médicale (INSERM), Lyon, France
7Albert Einstein College of Medicine
[Abstract # 27, p. 34]
11:00 – 11:30 a.m.
Chronic administration of 2-hydroxypropyl beta cyclodextrin directly into the CNS of
NP-C mice greatly delays neurodegeneration
Benny Liu, Stephen D. Turley, Dennis K. Burns, John M. Dietschy
UT Southwestern Medical Center
[Abstract # 28, p. 35]
11:30 – 12:00 a.m.
Altered energy metabolism in Niemann-Pick Type C1-deficient murine brain
Barry E. Kennedy1, Tiffany Mailman1, Debra Fice1, Ian Burton2, Tobias Karakach2,
Barbara Karten1
1Department of Biochemistry and Molecular Biology, Dalhousie University
2Institute of Marine Biosciences, National Research Council, Halifax, Canada
[Abstract # 29, p. 36]
6
12:00 – 12:30 p.m.
Cell-specific pathologic changes in retinae of NP-C deficient mice
Nicole Ungerer1, Valérie Demais2, Martine Perraut1, Sophie Reibel3,
Frank Pfrieger1
1Institute of Cellular and Integrative Neurosciences, University of Strasbourg
2Plateforme Imagerie in Vitro, Strasbourg, France.
3Chronobiotron, CNRS University of Strasbourg
[Abstract # 30, p. 37]
12:30 p.m.
Closing comments
Cindy Parseghian
Ara Parseghian Medical Research Foundation
12:45 – 1:45 p.m.
LUNCH
Jordan Hall Galleria
7