Progress Report: The Wellstone Centers and Other NIH Supported Muscular

Dystrophy Research Grants!

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!

PPMD 2010 Connect Conference!June 25, 2010!

The National Institutes of Health

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)

•  27 different Institutes and Centers

•  $31.2 billion annual budget

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

NIH Investments in Muscular Dystrophy Research

0

10

20

30

40

50

60

70

FY07 FY08 FY09na

other MD FSHD DM DBMD

$66M

$ M

illio

ns

$58M $56M

$23M $22M $29M

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

0

10

20

30

40

50

60

70

80

90

FY07 FY08 FY09tot

other MD FSHD DM DBMD $

Mill

ions

$58M $56M

$23M $22M

$83M

$33M

FY09 NIH Grants for the Muscular Dystrophies

$83M total

Wellstone Centers $8.7M

Multi-project grants $6.3M

Translational grants $8.5M

Small business $1.0M

Other $5.9M Investigator initiated single project grants $42.2M

ARRA short-term grants $8.0M

Training/career dev $2.2M

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

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

Features of the Wellstone Centers Program

Steering Committee

•  Directors and Co-Directors of each Center and NIH Program Directors

•  Regular teleconference meetings

•  Annual meeting at a Wellstone Center

Rochester Pittsburgh

Seattle

North Carolina

Boston Rochester

Iowa Penn/Hopkins

Children’s National (DC)

Wellstone Centers Awards

2003 2005 2007 2009 2011 2013

NIAMS NINDS NICHD

2015

NHLBI

Iowa Penn

Nationwide Children’s (OH)

NIH expects to make these awards in 2010

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