Progress Report: Wellstone Centers

Progress Report: The Wellstone Centers and Other NIH Supported Muscular Dystrophy Research Grants!

PPMD 2010 Connect Conference!

June 25, 2010!

Glen Nuckolls, PhD! Program Director for Muscle Diseases!

National Institute of Arthritis and Musculoskeletal and Skin Diseases!

National Institutes of Health!

US Dept. of Health and Human Services! nuckollg@mail.nih.gov!

The National Institutes of Health •

27 different Institutes and Centers

•

$31.2 billion annual budget

•

80% of NIH’s funding goes to competitive research grants

Main institutes supporting muscular dystrophy research: •

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

•

National Institute of Neurological Disorders and Stroke (NINDS)

•

Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)

•

National Heart, Lung and Blood Institute (NHLBI)

NIH Investments in Muscular Dystrophy Research $66M

70 60

$58M

$56M

50 other MD FSHD DM DBMD

$ Millions

40 30 20 10

$23M

$22M

$29M

FY07

FY08

FY09na

0

American Recovery and Reinvestment Act (ARRA) $10.4 billion provided to NIH to: • stimulate the economy • create and preserve jobs • advance biomedical research Support for new, short-term projects: • Challenge Grants • Grand Opportunity Grants • Additional standard grants Support to expand or supplement existing grants Support for new faculty positions and summer research training experiences

NIH Investments in Muscular Dystrophy Research 90

$83M

80 70

$ Millions

60

$58M

$56M

50

other MD FSHD DM DBMD

40 30 20 10

$23M

$22M

$33M

FY07

FY08

FY09tot

0

FY09 NIH Grants for the Muscular Dystrophies Training/career dev $2.2M

Wellstone Centers $8.7M

ARRA short-term grants $8.0M

Multi-project grants $6.3M

Translational grants $8.5M

Small business $1.0M Investigator initiated single project grants $42.2M

Other $5.9M

$83M total

http://report.nih.gov

Paul D. Wellstone Muscular Dystrophy Community Assistance, Research and Education Amendments (MD-CARE Act)!

Public Law 107-84 of 2001 and Public Law 110-361 of 2008 • Muscular Dystrophy Coordinating Committee (MDCC) • MD Surveillance Tracking and Research Network (MD STARnet) • Comprehensive DMD Care Considerations • Wellstone Muscular Dystrophy Research Centers Paul D. Wellstone 1944-2002 Senator from MN 1991-2002

Features of the Wellstone Centers Program Components of each Center • One or more projects related to a common translational or clinical research theme for the muscular dystrophies • A core to enhance the training of junior researchers and to educate and involve patients and families • Core facilities to support the projects and provide resources for the National MD research community Steering Committee • Directors and Co-Directors of each Center and NIH Program Directors • Regular teleconference meetings • Annual meeting at a Wellstone Center

Wellstone Centers Awards Pittsburgh Rochester Seattle Penn/Hopkins Iowa Children’s National (DC) North Carolina Rochester Boston NIH expects to make these awards in 2010 2003

2005

2007 NIAMS

2009 NINDS

Penn Iowa Nationwide Children’s (OH) 2011 NICHD

2013 NHLBI

2015

Wellstone Center at the University of North Carolina Jude Samulski, Bill Powers, Xiao Xiao, Joe Kornegay, Jeffrey Beecham Focus: Gene therapy for DMD and other dystrophies Progress on Research Projects: • Advances in viral vector mediated gene therapy in dystrophic mice and dogs • Conducting a clinical study in BMD and LGMD patients to learn how to safely push fluids from the blood vessels into the muscles of the leg and arm.

Wellstone Center at Children’s National Medical Center Eric Hoffman; Bob Leshner, Yi-Wen Chen, Kanneboyina Nagaraju, Terence Partridge Focus: Understanding the pathophysiology of DMD Progress on Research Projects: • Led the effort to publish standard operating procedures for muscular dystrophy animal testing • Morpholino antisense oligonucleotide exon-skipping in a dog model of DMD (Yokota et al., 2009, Ann Neurol)

Wellstone Center at the University of Pennsylvania Lee Sweeney, Elizabeth McNally, Melissa Spencer, Glenn Walter, Krista Vandenborne, Beth Barton, Michael Ostap Focus: Skeletal muscle and heart fibrosis in muscular dystrophies Previous progress: • Tested strategies to block muscle degeneration and promote muscle growth in mice • Piloted magnetic resonance imaging (MRI) and spectroscopy as outcome measures for DMD

Wellstone Center at the University of Iowa Kevin Campbell, Steven Moore, Katherine Mathews, Carsten Bonnemann Focus: Dystroglycan-related muscular dystrophies Previous progress: Sildenafil reduces exercise induced fatigue and muscle edema in a dystrophic mouse model (Kobayashi et el., 2008 Nature)

Wellstone Center at the Research Institute at Nationwide Children’s Hospital, Columbus OH Jerry Mendell, Chris Walker, Zarife Sahenk, Paul Martin Focus: Immune Response to Gene Therapy Previous Studies: • Gene therapy trial for Limb-Girdle muscular dystrophy type 2D (Mendell et al., 2009 Ann Neurol) • Gene therapy trial for Duchenne muscular dystrophy

www.wellstonemdcenters.nih.gov

Summary  NIH supports basic, translational and clinical

research on Duchenne/Becker and other muscular dystrophies.  The Wellstone Centers are focused on translational

and clinical studies in the dystrophies, and provide support for training, outreach and shared research resources.  Support for muscular dystrophy research is

enhanced by collaborative interactions among several NIH institutes, PPMD and other voluntary health organizations.

Acknowledgements  NIAMS Amanda Boyce NINDS John Porter Amelie Gubitz NICHD Jim Hanson Ljubisa Vitkovic NHLBI Jon Kaltman

Muscular dystrophy researchers Research participants and their families