LDN WORLD Symposium 2008

WORLD Symposium 2008 Preliminary Program
Subject to change

TUESDAY
February 12, 2008

Satellite Meeting

Hunter Outcome Survey (HOS) - Shire Genetic Therapies, Inc. (by invitation only, contact: Carol Cannon, ccannon@shire.com)
Shire HGT HOS meeting: 8:00 a.m. - 4:30 p.m.
Shire HGT HOS dinner: 5:15 p.m.

Satellite Meeting

Summit Meeting for Lysosomal Disease Patient Groups - organized by the Hide & Seek Foundation (by invitation only, contact: Stephanie Lyn, stephanie@hideandseek.org) 2:30 p.m. - 7:00 p.m.

WEDNESDAY
February 13, 2008

BASIC AND BENCH RESEARCH

Session 1
Wednesday Morning

Pathophysiology of
Lysosomal Diseases

Steven Walkley,
Don Mahuran,
Co-Chairs

8:30

Chester Whitley
University of Minnesota, Minneapolis, MN

Welcome

8:45

Edwin Kolodny
New York University School of Medicine, New York, NY

Keynote Address:
"Reflections On The Current State of Diagnosis For LSDs"

9:00

Susan Slaugenhaupt
Massachusetts General Hospital/Harvard Medical School, Boston, MA

A murine model for mucolipidosis type IV

9:15

Tyler Mark Pierson
Neurogenetics Branch, NINDS/NIH, Bethesda MD

Novel mutations in juvenile Sandhoff disease presenting as motor neuron disease

9:30

David Priestman
Department of Pharmacology, University of Oxford, Oxford UK

Glycosphingolipid profiling of tissues from mouse models of human lysosomal storage disorders.

9:45

Discussion

10:00

Break

10:15

Tim Edmunds
Genzyme Corporation, Framingham, MA

Biochemical characterization of the N370S glucocerebrosidase mutant: Implications for chaperone therapy

10:30

Kathleen Hruska
MGB, NHGRI, NIH, Bethesda, MD

Functional evaluation of predicted regulatory sequences at the GBA locus

10:45

Richard Steet
University of Georgia, Athens, GA

Altered chondrocyte differentiation in mucolipidosis II zebrafish

11:00

Margaret McGovern
Stony Brook University, Stony Brook, NY

Skeletal manifestations in Niemann-Pick disease due to acid sphingomyelinase deficiency

11:15

Edward Schuchman
Mount Sinai School of Medicine, New York, NY

Mouse models for types A and B Niemann-Pick disease: Insights into pathogenesis and treatment

11:30

David Pearce
University of Rochester, Rochester, NY

Moving toward therapies for JCNL

11:45

Discussion

12:00

Lunch on your own

Session 2
Wednesday Afternoon

Future Therapeutic
Approaches

David Pearce,
Edward Schuchman,
Co-Chairs

1:00

Dwight Koeberl
Duke University Medical Center, Durham, NC

Muscle-targeted gene therapy in glycogen storage disease type II with adeno-associated virus serotypes 7,8, and 9

1:15

Perry Hackett
University of Minnesota, Minneapolis, MN

Comparison of gene expression in vivo from Sleeping Beauty transposons after hydrodynamic delivery or condensation by polyethylenimine and cationic lipids

1:30

Don Mahuran
Hospital For Sick Children, Toronto, ON, Canada

Identification of Ambroxol as a potential enzyme enhancement-agent for Gaucher disease

1:45

Ozlem Goker Alpan
MGB, NHGRI, NIH, Bethesda, MD

The contribution of lysosomal pathways to the pathogenesis of common neurodegenerative disorders: Glucocerebrosidase and the synucleinopathies

2:00

Mia Horowitz
Tel Aviv University, Ramat Aviv, Israel

The possible implication of lowering cholesterol level in Gaucher disease patients

2:15

Catherine Kielar
Institute of Psychiatry, King's College London, UK

Reactive and synaptic changes precede neuronal loss in mouse models of NCL

2:30

Jonathan Cooper
Institute of Psychiatry, King's College London, UK

Immunosuppression as a novel therapeutic target in Batten disease

2:45

Discussion

3:00

Break

3:15

Walter Low
University of Minnesota, Minneapolis, MN

Targeting neural stem cells in the mammalian brain with intraventricular injections of lenti, AAV5, or Sleeping Beauty vectors

3:30

Charles Pontikis
King's College London, UK

In situ perfusion in a mouse model of Sanfilippo syndrome

3:45

Mark Haskins
University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA

Intrathecal enzyme therapy in mucopolysaccharidosis I cats reduces storage throughout the brain

4:00

R. Scott McIvor
University of Minnesota, Minneapolis, MN

Gene therapy of mucopolysaccharidosis type I: Intraventricular administration of adeno-associated virus vector transducing the human alpha-L-iduronidase gene in a murine model of the disease

4:15

Edward Ginns
University of Massachusetts Medical School, Shrewsbury, MA

Development of a novel ingestible macrophage-targeted gene therapy for Gaucher disease

4:30

Poster Session

6:00

Poster Session Adjourns

Satellite Meeting
6:00 - 7:00PM
Venetian Hotel

Patient Advocate Group (PAG) Meeting - Lysosomal Disease Network (open - please RSVP to David Erickson at info@lysosomaldiseasenetwork.org)

THURSDAY
February 14, 2008

LYSOSOMAL DISEASE NETWORK

Session 3
Thursday Morning

Research Projects

Chester Whitley, Chair

8:30

Introduction and Overview

9:10

LDN Research Projects

9:30

LDN Research Cores

10:00

Break

Measurement of Disease
Progression Panel

Edward Giannini,
Elsa Shapiro,
Co - Chairs

10:45

Edward Giannini
Cincinnati Childrens Hospital, Cincinnati, OH

Development of a disease severity scoring system for Anderson-Fabry disease

10:55

Nicole Yanjanin
NICHD, NIH, DHHS, Bethesda, MD

Disease progression in Niemann-Pick disease, type C: Longitudinal

11:05

Edward Giannini
Cincinnati Childrens Hospital, Cincinnati, OH

Development of a disease severity scoring system for patients with Pompe disease

11:15

Jennifer Kwon
University of Rochester Medical Center, Rochester, NY

Quantifying the rate of neurologic decline in Batten disease in clinical trials

11:25

Ari Zimran
Shaare Zedek Medical Center, Jerusalem, Israel

Development of a disease severity scoring system for type I Gaucher disease

11:35

Discussion

11:50

Lunch Break

Session 4
Thursday Afternoon

Newborn Screening Panel

Rodney Howell,
John Barranger,
Co - Chairs

1:00

Rodney Howell
Special Assistant to the Director, NICHD, NIH

Introduction

1:10

Michele Caggana
NYSDOH/Wadsworth Center, Albany, NY

Newborn screening for Krabbe disease in New York state: Experience from the first year

1:20

Joan Keutzer
Genzyme Corporation, Framingham, MA

An update on newborn screening for Pompe disease

1:30

Olaf Bodamer
University Children's Hospital, Vienna, Austria

Newborn Screening in Austria

1:40

Christiane Auray-Blais
Universiti de Sherbrooke, Sherbrooke, Quebec, Canada

Mass urinary screening for Fabry disease: Is it feasible?

1:50

Victor De Jesus
Centers for Disease Control and Prevention

Recent developments on lysosomal storage disorder activities at the centers for disease control and prevention

2:00

Discussion

2:15

Break

Clinical Outcomes

William Wilcox,
Ellen Sidransky,
Co-Chairs

2:30

Elsa Shapiro
University of Minnesota, Minneapolis, MN

Neuropsychological function and neuroimaging in severe and attenuated mucopolysaccharidosis

2:45

Patricia Dickson
LA Biomed at Harbor-UCLA, Torrance, CA

Initial experience with intrathecal recombinant human alpha-L-iduronidase for spinal cord compression in two mucopolysaccharidosis I patients

3:00

Break

3:15

Jeanine Utz
University of Minnesota, Minneapolis, MN

Delayed infusion reactions associated with enzyme replacement therapies for lysosomal storage disorders.

3:30

Maria Escolar
University of North Carolina, Chapel Hill, NC

Long-term developmental follow-up of babies treated for infantile Krabbe disease with unrelated cord blood transplantation

3:45

Lynda Polgreen
University of Minnesota, Minneapolis, MN

Growth hormone therapy improves growth in Hurler syndrome with minimal effect on scoliosis, kyphosis, or genu valgum.

4:00

Christine Eng
Department of Molecular and Human Genetics, Houston, TX

Characterization of symptom onset and clinical events in patients with Fabry disease: findings from the Fabry Registry

4:15

Discussion

4:30

Poster Session

5:00

LDN Steering Committee meeting

6:00

Poster Session closed

6:30

Banquet

7:30

Banquet and Program conclude

FRIDAY
February 15, 2008

CLINICAL TRIALS

Session 5
Friday Morning

Spectrum of Clinical Outcomes

Robert Steiner,
Danilo Tagle, Co-Chairs

8:30

Presentation of 2007 LDN Award

8:45

Roscoe Brady
Scientist Emeritus, NINDS, NIH, Bethesda, MD

Keynote Address, 2008 LDN Awardee for Innovation and Accomplishment

9:15

Hans Andersson
Tulane University Medical School, New Orleans, LA

Clinical outcome following 8-year enzyme replacement therapy in 884 children with type I Gaucher disease (GD1)

9:30

David Lockhart
Amicus Therapeutics, Cranbury, NJ

Pharmacological chaperone treatment for lysosomal storage disorders

9:45

Jakub Tolar
University of Minnesota, Minneapolis, MN

Antioxidant neuroprotection with hematopoietic cell transplantation in cerebral adrenoleukodystrophy

10:00

Discussion

10:15

Break

10:30

William Wilcox
Cedars-Sinai Medical Center, Los Angeles, CA

Natural history of Fabry disease: Progression of the nephropathy in a large series of affected males and heterozygous females

10:45

Beth Thurberg
Genzyme Corporation, Framingham, MA

Pathology of Fabry nephropathy: Renal fibrosis may begin in adolescence

11:00

Elizabeth Jacklin
Royal Manchester Childrens Hopital,UK

The natural history of Niemann-Pick disease type C

11:15

Neal Weinreb
University Research Foundation for Lysosomal Storage Diseases, Coral Springs, FL

Effect of enzyme replacement therapy with imiglucerase (Cerezyme.) every 4 weeks in patients with type I Gaucher disease

11:30

Discussion

11:45

Lunch on your own

Session 6
Friday Afternoon

Gaucher Disease: Focus for Innovation

Joseph Muenzer,
Gregory Grabowski,
Co-chairs

1:00

Gregory Grabowski
University of Cincinnati College of Medicine, Cincinnati, OH

Dose-response relationships for enzyme replacement therapy with imiglucerase / alglucerase in patients with Gaucher disease type I

1:15

Ellen Sidransky
MGB, NGHRI, NIH, Bethesda, MD

The association between mutant glucocerebrosidase and Parkinsonism

1:30

Gregory Pastores
NYU School of Medicine, New York, NY

Clinical trials with miglustat in patients with type 1 Gaucher disease (GD1)

1:45

Einat Almon
Protalix Biotheraputics, Carmiel, Israel

Novel enzyme replacement therapy for Gaucher disease: On-going phase III clinical trial with recombinant human glucocerebrosidase expressed in plant cells

2:00

Ari Zimran
Shaare Zedek Medical Center, Jerusalem, Israel

36 months on treatment: Open-label phase I/II long-term study of enzyme replacement therapy (ERT) with “gene-activated" human glucocerebrosidase (GA-GCB) in patients with type I Gaucher disease

2:15

Brandon Wustman
Amicus Therapeutics, Cranbury, NJ

Pharmacological chaperone therapy for Gaucher disease: Mechanism of action, a survey of responsive mutations and phase I clinical trial results

2:30

Judith Peterschmitt
Genzyme Corporation, Cambridge, MA

Preliminary results of a phase II clinical trial of Genz-112638 in patients with type I Gaucher disease

2:45

Discussion

3:00

Break

Longitudinal Studies and Outcomes

Christine Eng,
Ed Wraith, Co-Chairs

3:15

Olaf Bodamer
University Children's Hospital, Vienna, Austria

Natural history and treatment of MPS I: The MPS I Registry

3:30

Maurizio Scarpa
University of Padova, Padova, Italy

Neurological manifestations of Hunter syndrome: Insights from HOS, The Hunter Outcome Survey

3:45

Michelle Wood
Great Ormand Street Hospital, London, UK

Changes in gait pattern as assessed by the GaitRite walkway system in MPS II patients undergoing enzyme replacement therapy.

4:00

Ed Wraith
Royal Manchester Children's Hospital, Manchester, UK

Miglustat in Niemann-Pick disease type C (NPC)

4:15

Barry Byrne
University of Florida, Gainesville, FL

The Pompe Registry: Centralized data collection to track the natural course of Pompe disease

4:30

Alison Skrinar
Genzyme Corporation, Cambridge, MA

Response to enzyme replacement therapy in 18 juvenile and adult patients with advanced Pompe disease

4:45

Discussion

5:00

Meeting Adjourns

Wednesday &
Thursday
4:30 - 6:00PM

POSTER SESSIONS

Heather Adams - Genotype-phenotype associations in juvenile neuronal ceroid lipofuscinosis (JNCL; CLN3) University of Rochester Medical Center, Rochester, NY, USA

Amelia Ahern-Rindell - Characterization of Ovine GM1 Gangliosidosis Using Immunofluoresence University of Portland, Portland, OR, United States

Hans Andersson - Clinical outcome following 8-year enzyme replacement therapy in 884 children with type 1 Gaucher disease (GD1) Hayward Genetics Center, Tulane University Medical School, New Orleans, LA, USA

Elena Aronovich - Sleeping Beauty transposon-mediated long-term alpha-L-iduronidase expression and correction of lysosomal pathology in NOD/SCID mice with MPS I University of Minnesota, Minneapolis, MN, USA

Lalitha Belur - Gene delivery and biodistribution in the brain and spinal cord following intrathecal administration of adeno-associated virus serotype 5 vector University of Minnesota, Minneapolis, MN, USA

Lee Bera - Adeno-associated virus gene therapy for Tay-Sachs disease University of Minnesota, Minneapolis, MN, USA

Alessandra Biffi - Hematopoietic stem cell based gene therapy for the treatment of metachromatic leukodystrophy: Towards clinical testing , Milan, , Italy

Brian Bigger - Developing a lentiviral gene delivery system in stem cells for the treatment of Sanfilippo syndrome (MPS IIIA) University of Manchester, Manchester, Manchester, UK

Kendra Bjoraker - A natural history study of hexosaminidase deficiency University of Minnesota, Minneapolis, MN, USA

Maud Bouvier - A novel approach for a specific delivery of glucocerebrosidase in bone marrow Gaucher cells ERYtech Pharma, Lyon, Rhone-Alpes, FRANCE

Lawrence Charnas - Serum biomarkers and clinical effect of off-label use of Miglustat in GM1 Gangliosidosis University of Minnesota, Minneapolis, MN, USA

Kathy Corley - Enzyme replacement therapy: Transitioning care into community or home Children's Hospital of Western Ontario/ London Health Sciences Centre, London, Ontario, Canada

Kristina Cusmano-Ozog - An unusual case of Pompe disease presenting as muscular dystrophy Stanford University, Stanford, CA, USA

Hung Do - Pharmacological Chaperone Treatment for Pompe Disease Amicus Therapeutics, Inc., Cranbury, NJ, USA

Colleen Doyen - Data collection tools for compiling accurate health histories University of Minnesota, Minneapolis, MN, United States

Serap Emre - Molecular analysis of Turkish Gaucher disease patients Department of Medical Biology, University of Hacettepe, Ankara, , Turkey

Christine Eng - Nephropathy in Fabry disease: Baseline characteristics of 1,262 patients in the Fabry Registry Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, Houston, TX, USA

Christine Eng - Characterization of symptom onset and clinical events in patients with Fabry disease: findings from the Fabry Registry Department of Molecular and Human Genetics, Houston, TX, USA

David Erickson - Application of information technology in multi-site collaborative endeavors University of Minnesota, Minneapolis, MN, United States

Niamh Finnegan - Girls just want to have fun! Great Ormond Street Hospital for Children NHS Trust, London, England, UK

Edward Giannini - Development of a Disease Severity Scoring System for Anderson-Fabry Disease , Cincinnati, OH, USA

Ozlem Goker Alpan - The contribution of lysosomal pathways to the pathogenesis of common neurodegenerative disorders: Glucocerebrosidase and the synucleinopathies MGB/NHGRI/NIH, Bethesda, MD, USA

Gregory A. Grabowski - Guidelines for the assessment and monitoring of bone disease in children with Gaucher disease Cincinnati Children_s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA, Cincinnati, OH, USA

Susan Hale - Quality-of-life changes in MPS II patients receiving enzyme replacement therapy Children's Hospital and Regional Medical Center, Seattle, Washington, Seattle, WA, USA

Nadene Henderson - The transition from childhood to adulthood in patients with lysosomal storage disorders , Pittsburgh, PA , USA

Robert J. Hopkin - Characterization of Fabry Disease in 283 Pediatric Patients in the Fabry Registry Cincinnati Children's Hospital Medical Center, Division of Human genetics, Cincinnati, OH, USA

Zhang Huiwen - One-year experience of enzymatic diagnosis of lysosomal storage diseases in China Shanghai Institute of Pediatric Research,Xihuan Hospital, Shanghai Jiaotong University, Shanghai, Kongjiang Road , P.R.China

Nikhil Iyengar - Myocardial infiltration in Anderson-Fabry disease: _ A case report Department of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Rachel Katz - A home infusion protocol for MPS II patients on enzyme replacement therapy (ERT) Children's Memorial Hospital, Chicago, IL, Chicago, Illinois, USA

Joan Keutzer - An improved dried blood spot screening method for Gaucher disease Therapeutic Protein Research, Genzyme Corporation, Framingham, MA, Cambridge, MA, USA

Richie Khanna - The pharmacological chaperone AT1001 and treatment of Fabry disease Amicus Therapeutics, Cranbury, NJ, USA

Priya Kishnani - Effect of dose of enzyme replacement therapy with imiglucerase on bone crises in adolescents with Gaucher disease Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, NC, USA

Edwin Kolodny - A novel GM2-activator deficiency mutation as a cause of AB variant GM2-Gangliosidosis New York University School of Medicine, New York, New York, USA

Edwin Kolodny - GM1-Gangliosidosis in an American Black Bear New York University School of Medicine, New York, New York, USA

Edwin Kolodny - Clinical and demographic characteristics of 131 patients with neuronopathic Gaucher disease enrolled in the Neurological Outcomes sub-registry of the ICGG Gaucher Registry New York University School of Medicine, New York, NY, USA

Dawn Laney - Reproductive fitness in individuals affected by Fabry disease Emory University, Decatur, GA, USA

Alexander Lewis - Inhibition of the nicotinic acid adenine dinucleotide phosphate receptor induces a novel lysosomal storage disease University of Oxford, OXFORD, Oxon., UK

Adriana Linares - Gaucher Registry: A comparison among Argentina, Brazil and Colombia 2007 country reports Universidad Nacional de Colombia, Bogota, Bogota, D.C., Colombia

Emyr Lloyd-Evans - Smith-Lemli-Opitz syndrome: A closet lysosomal storage disease hiding within an inheritable metabolic disorder of cholesterol biosynthesis University of Oxford, Oxford, Oxon, United Kingdom

Emyr Lloyd-Evans - Abnormal lysosomal calcium homeostasis in mucolipidosis type IV University of Oxford, Oxford, Oxon, United Kingdom

Deborah Marsden - Development of a disease severity scoring system for patients with Pompe disease Genzyme Corporation, Cambridge, MA USA, Cambridge, MA, USA

R. Scott McIvor - Gene therapy for lysosomal storage disorders , Minneapolis, MN, U.S.A.

Klary E Niezen-Koning - Nonmodified siRNA leads to downregulation of alpha-glucosidase: Towards a mouse model for Pompe disease Dept Path Lab Med, Metab Dis, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen (UMCG), University of Groningen, the Netherlands, Groningen, Groningen, The Netherlands

Nina Raben - A new look at pathogenesis of Pompe disease , Bethesda, MD, USA

Sherri Sandberg - Pseudo-deficiency allele of the N-acetylgalactosamine-4-sulfatase gene identified in a family with Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI) University of Minnesota, Minneapolis, MN, USA

Swati Sathe - Homozygosity for a tandem mutation (D409H and H255Q) leads to acute neuronopathic Gaucher disease New York University School of Medicine, New York, New York, NY, US

Maurizio Scarpa - Neurological examinations and clinical manifestations in MPS I Registry patients Center of Rare Disorders, University of Padova, Padova, , ITALY

Maurizio Scarpa - Brains For Brain: A new consortium for the research and the therapy of LSDs Department of Pediatrics, University of Padova, Padova, , ITALY

Maurizio Scarpa - In vivo evaluation of genistein for GAG storage reduction Department of Pediatrics, University of Padova, Padova, , ITALY

Maurizio Scarpa - A zebrafish iduronate 2-sulfatase candidate orthologue is strongly expressed during early embryonic development Department of Pediatrics, University of Padova, Padova, , ITALY

Patricia Schachern - Functional and histopathological age-related changes of the ear in the MPS IIIB mouse University of Minnesota, Minneapolis, MN, USA

Edward Schuchman - Structural & functional properties of four common mutations causing acid sphingomyelinase-deficient Niemann-Pick disease Mount Sinai School of Medicine, New York, NY, United States

Paul Score - Lentiviral vector optimization for IDUA expression in the murine model of Hurler syndrome (mucopolysaccharidosis type I) University of Minnesota, Minneapolis, MN, USA

Calogera Simonaro - Mechanism of glycosaminoglycan-mediated bone and joint disease in the mucopolysaccharidoses Mount Sinai School of Medicine, NY, NY, United States

Fiona Stewart - Treatment of lysosomal storage disorders in Northern Ireland Northern Ireland Regional Genetics Service, Belfast, Northern Ireland, United Kingdom

Jakub Tolar - Long-term outcome of hematopoietic cell transplantation for Wolman disease University of Minnesota, Minneapolis, MN, USA

Jakub Tolar - Niemann-Pick disease: Survival after umbilical cord blood transplantation University of Minnesota, Minneapolis, MN, USA

Michael Tropak - Effects of novel beta-glucocerebrosidase enhancers and pharmacological chaperones on protein stability/dynamics probed by hydrogen-deuterium exchange mass spectrometry Hospital for Sick Children, Toronto, ON, CANADA

Jeanine Utz - Delayed infusion reactions associated with enzyme replacement therapies for lysosomal storage disorders. University of Minnesota, Minneapolis, MN, U.S.A.

Ilaria Visigalli - Development of an effective and safe hematopoietic stem cell gene therapy for Globoid Cell Leukodystrophy: The unexpected issue of GALC toxicity , Milan, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Italy

Neal Weinreb - Increased risk of osteopenic fractures in elderly patients with Gaucher disease University Research Foundation for Lysosomal Storage Diseases, Coral Springs, FL, USA

Daniel Wolf - Syngeneic bone marrow transplantation in a murine model of mucopolysaccharidosis type I Department of Genetics, Cell Biology, and Development. University of Minnesota-Twin Cities, Minneapolis, MN, USA

Durhane Wong-Rieger - Challenges of LSD treatment: The patient experience Canadian Organization for Rare Disorders, Toronto, Ontario, Canada

Michelle Wood - Observed changes in behaviour with assessment and procedures in neurologically affected boys with mucopolysaccharidosis type II undergoing enzyme replacement therapy Great Ormond Street Hospital London, London, , UK

Ed Wraith - Safety monitoring of miglustat in patients with Niemann-Pick disease type C Royal Manchester Children_s Hospital, Biochemical Genetics Unit, Manchester, UK, Manchester, Lancashire, UK

Xiaoyang Wu - Identification of Fabry disease-causing mutations that are responsive to the pharmacological chaperone AT1001 Amicus Therapeutics, Cranbury, NJ, USA

Yotam Blech Hermoni - Analysis of enzyme activities of different lysosomal enzymes in brain samples from subjects with Parkinson disease
MGB,NHGRI,NIH, Bethesda, MD, USA

Richard Ziegler - Neurobehavioral core University of Minnesota, Minneapolis, MN, USA