PPMD Connect Conference 2012

Florida

Jodi Wolff, MSSW

Muscular Dystrophy Association

Director of Clinical Services

Overview • MDA Clinical Program • MDA Research Program • MDA Clinical Research Network

– Goals – Research

200 MDA Clinics Nationwide

MDA Clinic MDA ALS Clinic

200 MDA Clinics Nationwide

•  Inherent infrastructure & network •  Grant funding

– What is “covered” in clinic? •  MDA Health Care Service

Coordinators

MDA Services •  Clinic & research •  Education •  Support groups •  Educational advocacy, IEP meetings •  Equipment repairs & loan •  Transitional services

Canada

United States

Australia

Japan Spain

France

United Kingdom

Ireland

Israel

Singapore

Sweden Belgium

Netherlands

Greece

Germany

Italy

Switzerland

MDA’s Global Research Program MDA supports research aimed at developing treatments for the muscular

dystrophies and related neuromuscular diseases.

MDA’s Research Portfolio Investment in research and researchers

Basic Research Target Identification Drug Screening

“Proof-of-Principle” Testing in Animals

Translational Research “Preclinical Drug

Development” Clinical Research Including Trials

Research Grant Portfolio

•  Research grants

•  Training grants

•  Clinical trials / studies

•  Translational research grants (MVP)

•  Misc (infrastructure, special grants)

MDA Research Program •  288 active grants (88 DMD) •  33 additional up for approval •  Rigorous review process – MAC/SAC •  $35 million/year new funds •  75-100 new awards/year •  ~$350K over 3 years

Role of MDA in DMD •  In 2012, 88 active grants •  $32 million in DMD research funding •  February 2012 – 14 grants = $4.1m •  >$110m since 1997 •  >$60m for DMD therapies

MDA’s Training Mission

•  Development Grants v Training future NMD researchers

•  Clinical Research Training Grants v Training future NMD clinicians

•  Mentored fellowships; $180K (2-3 yrs) •  Currently 40 trainees (>$7M; ~15% clinicians) •  Outreach efforts – e.g. AAN •  NMD leaders

Preclinical Human Trials Phase I Phase II Phase III

Discovery

MDA contribution

Technology Company

DMD alpha7 Integrin

Antioxidant

Exon skipping

Glutamine/creatine

Mitochondrial pore

Myostatin inhib

NF-kB inhibition

NO stimulation

Utrophin upregulation

Pentoxifylline

Membrane sealant

Glucocorticoids

Gene Therapy: AAV Nonsense Suppression

Antifibrotic

Losartan

Cell Transplant

Laminin-111

Muscle Growth

Stem Cells Utrophin gene therapy

PGC-1alpha

Santhera

Prosensa/GSK, AVI Biopharma, etc AMT, Genzyme, Asklepios, etc.

Debiopharm, Scynexis

Acceleron, Orico, PTC, Pfizer etc.

PTC Therapeutics, UCLA etc.

Children’s Research Institute

Children’s Research Institute

Prothelia

Phrixus, TRIM-edicine

Fate therapeutics

Avicena, NGM, Cortene Summit, Domain, PTC

PTC, Combinatorx, Prothelia etc.

Catabasis, Validus, Combinatorx etc.

University Hospital Milan, NicOx

Biglycan Tyversan

Cleveland Clinic Foundation, Genzyme

McGill University

University of Basel

University of Ottawa PPARdelta

Proteasome inhibition Thomas Jefferson University

Nationwide Children’s Hospital UDP-GalNac

Promimetic, Fondazione San Raffaele

Johns Hopkins University

Orig: Schering-Plough, Shire etc.

Calpain inhib. Ipsen, CepTor, Rose Pharmaceuticals

prednisone idebenone glutamine/ creatine

ACE-031 ataluren

biostrophin GSK-051, eteplirsen

P-188

pentoxifylline

mesangioblasts SMT-C1100

Laminin-111

isosorbide dinitrate biglycan

losartan

Myodur

Albuterol UCLA albuterol

Mast Cell Stabilization CNRG oxatamide

PTC IGF-1 upregulation

Androgen antagonists Galapagos GLPG0492

DMD-02

Increased Blood Flow Cedars Sinai Medical Center sildenafil / tadalafil

200 MDA Clinics Nationwide 5 networked DMD clinical research centers

MDA Clinic MDA ALS Clinic Duchenne research network

MDA’s DMD Clinical Research Network Centers: Boston Children’s – Dr. Basil Darras Nationwide Children’s – Dr. Jerry Mendell Washington University – Dr. Anne Connolly University of Minnesota – Dr. John Day UC – Davis – Dr. Craig McDonald

MDA Clinical Research Network Goals

1.  Support development of evidence-based standards of care

2.  Outcome measures 3.  Testing new treatments 4.  Regional collaboration

MDA Clinical Research Network Cardiomyopathy

q Assessment & treatment of dystrophin-

deficient cardiomyopathy q Establish echocardiography standards q Natural history q Clinical trial of losartan vs lisinopril q Genotype-phenotype correlation

MDA Clinical Research Network Outcome Measures

q Development of outcome measures for

DMD < 5 years of age q Outcome measures for non-ambulatory

individuals

q Regional outreach meetings - annually

The Changing Face of DMD