john h. ferguson md, medical consultant, ordr/ncats/nih
TRANSCRIPT
RARE DISEASES RESEARCH AT NIHNCATS, TRND AND ATAXIA RESEARCH
John H. Ferguson MD, Medical Consultant, ORDR/NCATS/NIH
PRESENTER DISCLOSURES
No relationships to disclose or list
AGENDA
Rare Diseases Office of Rare Diseases Research
(ORDR) National Center for Advancing
Translational Sciences – NCATS Therapeutics for Rare and Neglegted
Diseases –TRND Ataxia research with ORDR, NCATS and
TRND
RARE DISEASES
18 - 25million people in the US are affected - Exact Prevalences Unknown
Estimated 6%-8% of Population Prevalence definition: < 200,000 people in the USA > 7000 Genetic and Acquired Rare Diseases Need Collaborative Efforts of the Rare Diseases Community
Academic Researchers Federal Research and Regulatory Programs > 1100 Patient Advocacy Groups/Philanthropic
Foundations Industry
Congressional Rare Diseases Caucus Established
RARE DISEASES CLINICAL RESEARCH NETWORK
19 Consortia supported by ORDR, NINDS, NIAMS, NICHD, NHLBI, NIDDK, NIAID, NIDCR and NCI
Required 3 diseases
longitudinal studies of patients,
Encouraged : Phase I, II and III trials;
Training of Investigators in clinical research of rare diseases;
Pilot studies/demonstration projects
Collaboration with Patient Advocacy Groups Data Management Coordinating Center DMCC > 192 Institutions World-wide, 42 International Sites, > 200
Diseases 9393 patients enrolled in 68 studies
• Collaborative Clinical Research
• Public Resources and Education
• Centralized Data Coordination and
Technology Development
• Training
The Data Management and Coordinating Center
Coalition of PatientAdvocacy Groups
(CPAG)
Chronic Graft Versus Host Disease Consortium
CREATION OF THE NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES (NCATS)
To catalyze the development of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions
Clinic AccessPhase
iv
DEVELOPMENT OF NEW THERAPEUTICS
Phase I
Phase III
Phase II
Stage 1Drug Discovery
Stage 2Pre-clinical
Stage 3Clinical Trials
Stage 4FDA Review
6.5 years 6 years 1.5 years
IND Submitted
NDA Submitted
NCATS RESEARCH PROGRAMS Components of Molecular Libraries Program Therapeutics for Rare and Neglected Diseases Office of Rare Diseases Research Bridging Interventional Development Gaps
(BrIDGs) Clinical and Translational Science Awards
(CTSA) FDA-NIH Regulatory Science Cures Acceleration Network
NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCINECES
NCATS STRUCTURE
Division of Pre-Clinical
InnovationChris Austin
Division of Clinical
Innovation Josie Briggs
(Acting)
Office of the Director
Tom Insel (Acting Director)
Kathy Hudson (Acting Deputy
Director)
Executive Office
Erin Shannon (Acting)
Office of Grants
Management & Review
Jane Steinberg (Acting)
Office of Policy, Communications,
& Strategic Alliances
Kathy Hudson (Acting)
Council CAN Board
Office of Rare Diseases Research
Steve Groft
NCATS UNIFIES THREE PROGRAM AREAS
Clinical and Translational Science Activities CTSAs Clinical Translational Science Awards
Rare Diseases Research and Therapeutics Office of Rare Diseases Research ORDR Therapeutics for Rare and Neglected Diseases
(TRND) Re-engineering Translational Sciences
NIH Chemical Genomics Center/Molecular Libraries program
Bridging Interventional Development Gaps BrIDGs Toxicology in the 21st Century
TRND PARTNERS
Academia Government Biopharmaceuticals
Patient Advocacy Groups
TRND Successful applicants don’t receive grants
Form joint project teams with TRND
Receive in kind support from TRND
scientists, laboratory and contract
resources
Goal is advancing compounds to FDA IND
clinical trials in humans
TRND PILOT PROJECTS, PROOF OF CONCEPT
Niemann- Pick C
Hereditary Inclusion Body Myopathy
Sickle cell anemia - IND received
Chronic Lymphocytic Leukemia IND
received
Shistosomiasis
TRND – 4 DRUG DEVELOPMENT PROJECTS APPROVED
Duchenne Muscular Dystrophy
Fragile X
Cryptococcal Meningitis
Core binding factor leukemia
LATEST TRND PROJECTS APPROVED
An inhibitor compound for Rx of fibrodysplasia ossificans Applicant is academic MD Compound shows efficacy in mouse model
Novel Rx for creatine transporter deficiency Applicant is a pharmaceutical Co. Mouse model show incr. brain metabolism and
cognative function Compount for Rx of neonatal herpes simplex
Applicant is academic pediatrician Compound can penetrate CNS, NIAID studied
LATEST TRND PROJECTS APPROVED
Deuterimum modified compound for shistosomiasis Applicant is pharmaceutical co. Enables lower and less frequent dosing
Drug candidate for Duchenne MD Applicant is pharmaceutical co. Drug is for a specific subgroup mutation
Rx for autoimmune pulmonary alveolar proteinosis Applicant is academic MD Developed as an inhaled Rx
TRND WILL FOLLOW MILESTONES AND TERMINATE PROJECTS – FOR INSTANCE
If no effect in animal models
Too much toxicity in preclinical testing
Poor bioavailability – can’t be absorbed
OTHER NCATS PROGRAMS
Cures Acceleration Network (CAN) Address challenges that impede translational
research Rescuing and Repurposing Drugs e.g.
lithium Designing a Tissue Chip for Drug Screening
With FDA and the Defense Advanced Research Projects Agency (DARPA)
“organ on a chip” Identifying and Validating Drug Targets
NCATS, ORDR AND ATAXIA RESEARCH
Many potential drug targets for new compounds heard at AIM 2012
High throughput screening at NCATS of thousands of molecules already being used by ataxia researchers
Rescuing and repurposing drugs is NCATS program and many examples given at AIM 2012
Programs at ORDR, NeuroNext, NCATS and TRND should offer HUGE opportunities for ataxia research ncats.nih.gov
NIH OFFICE OF RARE DISEASES RESEARCH - STAFF Steve Groft PharmD Ms. Mary Demory Dr. David Eckstein Ms. Marita Eddy (Angel Flight) Dr. John Ferguson Dr. Rashmi Gopal-Srivastava Mr. Christopher Griffin Ms. Henrietta Hyatt-Knorr Dr. Lata Nerurkar Ms. Susan Orr Lowe Ms. Geraldine Pollen Dr. Yaffa Rubinstein Dr. William Gahl (Clinical Director, NHGRI) Dr. P.J . Brooks (NIAAA)