Presentation on theme: "CCFA RESEARCH PROGRAMS, PRIORITIES and IBD Exchange"— Presentation transcript:
1CCFA RESEARCH PROGRAMS, PRIORITIES and IBD Exchange Balfour Sartor, MDChief Medical AdvisorMarjorie MerrickVice President, Research and Scientific Programs
2CCFA’s Mission and Vision Statements Mission: To cure Crohn's disease and ulcerative colitis, and to improve the quality of life of children and adults affected by these diseases.Vision: A future free from Crohn’s disease and ulcerative colitis.
3Very little research was conducted in the field of IBD. CCFA Has Invested $200 Million In Research Since How Have Things Changed?1967:Very little research was conducted in the field of IBD.Few therapies were available (primarily prednisone and sulfasalazine, segmental resection CD, ileostomy after total proctocolectomy UC).No genes had been identifiedFor many IBD patients, a stay in the hospital might run into weeks or even months.Self-explanatory
4How Have Things Changed? CCFA, NIH, medical centers and pharmaceutical companies around the world are actively conducting basic, clinical and translational research in IBD.CCFA has supported over 1400 research grants and currently funds approximately 200 ongoing and new grants annually.There are multiple drugs now available, including the biologics, and many experimental therapies in the pipeline.Over 163 genes have been associated with IBD.The average hospital stay for people with Crohn’s or colitis has been reduced to approximately 9 days.Self-explanatory
5Unmet Clinical Needs in IBD (Sartor perspective, not CCFA) Accurate prediction of disease course and response to treatment in an individual patientInduction and maintenance of remission in patients unresponsive to or intolerant of anti- TNF mAbInduction of remission of mild to moderate ileal Crohn’s disease without steroids or biologic therapies
6Unmet Clinical Needs in IBD (II) Sustained clinical remission in majority of patients that require steroids or anti-TNFs for inductionOptimal prevention of relapse in postoperative CD and pouchitis in UCIdentify clinically relevant subsets of patients with predictable clinical responses- individualized therapy. Mechanistic approachCure of CD and UC and prevention of onset of IBD in susceptible individuals
7CCFA ResearchApproximately 200 active grants per year (ongoing and new awards).Average of $16 million per year over past 4 yrs$21 million in 2014CCFA offers 2 levels of investigator-driven grants. Applications are accepted in January and July of each year and go through the rigorous peer-review process described in the previous slide.
8CCFA Research Programs Investigator- Initiated Research GrantsSenior AwardsCareer Development AwardsResearch FellowshipsResearch InitiativesMicrobiome InitiativeGenetics InitiativeRISK Stratification studyOSCCARCCFA Partners IBD ExchangeResearch ResourcesPROKIIDS networkClinical Research AllianceCCFA DNA BankCCFA Microbiome BioinformaticsCCFA Data Management CenterResearch PilotsBiomarkersPerioperative infectionsMucosal healing UCPROKIIDSQI
9CCFA Research Strategies Fund the best peer-reviewed research available.Train the next generation of IBD investigatorsHelp perpetuate the rapid progress in basic and clinical IBD research of the last decade by providing seed money to enable investigators to generate data to become competitive at NIHFacilitate early introduction of novel technology that has the potential to lead to paradigm shifting breakthroughs into IBD researchCCFA uses these strategies to accomplish the goals of “predict” and “cure”.We fund the best peer-reviewed research we can find, no matter where it is happening. Senior Research Awards have been funded in 15 countries around the globe. (Canada, England, Ireland, Switzerland, France, Germany, Sweden, Italy, Netherlands, Belgium, South Africa, Israel, Japan, Australia, New Zealand)Our training award programs (Career Development and Research Fellowship Awards) support outstanding young investigators interested in pursuing a career in IBD research.We provide seed money to enable investigators to generate data to become competitive for NIH grants.We identify and support emerging areas of research and novel technology that has the potential to lead to new breakthroughs.
10CCFA Research Strategies (II) 5. Identify host and microbial pathways that provide novel therapeutic approaches, then partner with pharmaceutical companies to develop new drugs6. Frequently update and prioritize research goals (Challenges in IBD), then widely publicize these research prioritiesCCFA uses these strategies to accomplish the goals of “predict” and “cure”.We fund the best peer-reviewed research we can find, no matter where it is happening. Senior Research Awards have been funded in 15 countries around the globe. (Canada, England, Ireland, Switzerland, France, Germany, Sweden, Italy, Netherlands, Belgium, South Africa, Israel, Japan, Australia, New Zealand)Our training award programs (Career Development and Research Fellowship Awards) support outstanding young investigators interested in pursuing a career in IBD research.We provide seed money to enable investigators to generate data to become competitive for NIH grants.We identify and support emerging areas of research and novel technology that has the potential to lead to new breakthroughs.
11Challenges 2013 CCFA’s Strategic Plan for Research Chairs: Ted Denson, Dermot McGovernGenetics: Dermot McGovern, Subra KugathasanMicrobiome: Balfour Sartor, Gary Wu, Vince YoungAdaptive Immunity: Theresa Pizarro, Ed deZoetenInnate Immunity: Thad Stappenbeck, Scott Plevy, Clara AbrahamEpithelial Cell Biology: Asma Nusrat, Declan McCole, Christian Jobin, Charles ParkosIBD Diagnosis: Ted Denson, Corey Siegel, Peter HigginsOptimizing Therapy: Hans Herfarth, Jeffrey HyamsEpidemiology/Environmental Factors: Ed Loftus, Mike Kappelman, Millie LongSince 1989, CCFA has brought together top IBD thought leaders to identify the most pressing unmet needs and unanswered questions in a variety of scientific areas. The resulting consensus paper, CHALLENGES IN IBD RESEARCH, outlines CCFA’s scientific strategic plan. The document is updated every 3-5 years, the most recent update was published in May 2013 in the IBD journal and posted CCFA’s website. Every project CCFA supports must address one or more of the priorities outlined in the document. The topics and workgroup chairs are listed on this slide.
12Challenges 2013Define clinically relevant subsets of patients with IBD using genetic, immunologic, microbial, tissue expression, and clinical profiles (to include drug levels) that will predict aggressiveness of disease, complications and response to treatment.Understand how environmental factors enhance risk of IBD through effects on microbial, epigenetic, immunologic, mucosal barrier influences – with an early focus on diet.The priorities listed in CHALLENGES 2013 are listed on this slide.
13Challenges 2013 (continued) Further understand reciprocal interactions (cross-talk) between genes, microbiota, epithelial cells, innate and adaptive immune responses that determine pathways mediating mucosal homeostasis versus inflammation.Determine which environmental triggers initiate, perpetuate, and/or reactivate disease.Determine optimal treatment strategies through comparative effectiveness studies.Continued from previous slide.
14Resources Identified as Essential Centralized and distributable infrastructure for biobanking, data warehouse, and tissue/cell/microbial repositories for integrated human investigation.Prospective cohort studies of pediatric and adult IBD patients with serial biospecimens collected throughout the course of their diseases.Infrastructure to recruit and follow patients from childhood to adult life.Access to data and biospecimens collected prior to and following treatment with established and novel therapeutics.Essential resources are listed on this slide.Infrastructure includes necessary technology, equipment, personnel (both scientific and administrative).Ability to collect, analyze and distribute data and specimens is key component.
15Resources Identified as Essential Improved tools for measuring disease activity in IBD.More specific in vivo tools including humanized mice and lineage specific models for mechanistic research.Availability of new methodology for improved cell lines and freshly isolated and viable mucosal cells.Implementation of a series of workshops to improve IBD research methodology and promote integrative multidisciplinary approaches and resources.Essential resources continued.
16Research InitiativesDesigned to fill important unmet needs in IBD research based on priorities described in Challenges in IBD Research:PROKIIDS IBD Research Network- RISK, PROTECTCCFA PartnersClinical Research AllianceGenetics InitiativeMicrobiome InitiativeIBD ExchangePRO-KIIDS IBD RESEARCH NETWORKFrancisco Sylvester and Mel Heyman – Co-chairsTwo ongoing studies:RISK (Subra Kugathasan – PI) – CCFA funded study in newly diagnosed Crohn’s patients; 5 abstracts accepted to DDW; 4 manuscripts in progress; 17 ancillary studies approvedPROTECT (Ted Denson – PI ) NIH funded study in UCCCFA Partners – Internet based registry of patient reported outcomes started in 2011Bob Sandler – PIOver 12,000 patients enrolled17 abstracts, 4 publications, 4 abstracts at DDWClinical Research AllianceHans Herfarth and Peter Higgins – Co-chairsOngoing studies:MERIT-UC (Hans Herfarth – PI)PIANO (Uma Mahadevan – PI)PUCCINI (Bruce Sands – PI)Mucosal Healing in UC Pilot grant (Mark Osterman – PI)GeneticsRamnik Xavier and Skip Virgin – Consortium Co-chairs (in planning phase)MicrobiomePhase 1-3: Jeff Gordon, PI – more than 50 publications to dateJon Braun – Phase 4 Consortium chair33 peer-reviewed publications, 15 submitted manuscripts, 9+ abstractsOSCCAR (Ocean State Crohn’s and Colitis Area Registry)Bruce Sands – PI430 newly diagnosed patients enrolled3 publications, 3 manuscripts submitted, 2 in progress; 14 abstracts, 2 oral presentations
17Pediatric Risk Stratification Project 26 centers have enrolled ~1100 newly diagnosed pediatric patients with Crohn’s disease (1754 overall pts: 70% Crohn’s disease, 15% UC, 5% indeterminant colitis, 10% controlsGoal: identify serum biomarkers, fecal bacteria, genes, immunologic and clinical patterns that predict at the time of diagnosis which child will develop severe, complicated vs. mild Crohn’s disease and which individual will respond to each medicationResources: Ileal and rectal biopsies on majority of pts (Illumina deep sequencing 16srRNA), fecal samples, tissue mRNA profiling (RNA seq), all pts genotyped (Immunochip), serology, prospective serial clinical phenotyping and therapeutic responsesBuilding a multi-center research consortium is especially important if we are to help the approximately 140,000 children and adolescents under 18 to overcome Crohn’s and colitis. We already know that treating these youngsters is hampered by a significant lack of scientific data on the use of the various therapies in young people because drug trials are not consistently performed in adolescents, and rarely with children under the age of 14.Like the Clinical Alliance, a multi-center consortia of leading pediatric researchers is urgently needed to enable researchers to address critical scientific knowledge gaps. CCFA’s Pediatric Research Network is starting with 7 centers in Hartford, Cincinnati, Atlanta, Philadelphia, Los Angeles, Milwaukee and Long Island, who have agreed to share data through a common database. These centers are collecting DNA, stool and serum samples from newly diagnosed patients under the age of 18 and will track these patients over time. For the initial study, the researchers hope to identify biomarkers that will help doctors to predict at the time of diagnosis which child will develop severe Crohn’s disease so that these children can be treated aggressively very early in the course of their disease. Early and aggressive treatment for children at high risk of developing severe disease may minimize symptoms and prevent future complications, as well as spare those who are likely to develop only mild to moderate disease to avoid the more powerful treatments that they really don’t need.
18Microbiome Consortium (2010- 2013) 7 multi-center, multi-disciplinary consortia studying large cohorts of Crohn’s disease, UC, normal and non-IBD subjectsExplore mechanisms by which genetic influences, AIEC, Paneth cells influence intestinal bacterial composition and function, IEC/ microbial interactions, viral triggers of disease onset/ flaresPerform mechanistic studies of CD gene regulation of gut bacteria in genetically engineered gnotobiotic miceRenewal ( ).Prospective cohorts ileal CD & UC serially sampled (bxs, stool metabolomics), functional verification of candidate pathways to identify targets, high throughput screens for candidate drugs
19Microbiome: Anticipated Outcomes Identify key microbial components that initiate and perpetuate diseaseFind biomarkers that can predict disease courseSelect subsets of patients that are likely (or unlikely) to respond to a particular treatmentDevelop novel ways to manipulate the microbiota to both treat and prevent disease (Better antibiotics, probiotics, diets, fecal or microbial transplants)Develop intervention strategies to prevent disease in high risk individuals (perhaps identified by their genetic and/ or microbial profiles)
20IBD Exchange Mission & Philosophy Mission - create an interconnected collection of patient information, biospecimens and knowledge to advance our understanding of the causes and lead to the discovery of a cure for IBD.Philosophy - the community who takes advantage of the resources will also contribute to building the resources by depositing their data, discoveries and newly created resources back into IBD EXCHANGE so that others can benefit from the new knowledge that has been developed.
21IBD Exchange GoalsProvide investigators with access to the resources needed to support their research.Facilitate sharing of knowledge more rapidly than relying on publication in peer-reviewed journals.Promote collaboration among investigators and sharing of clinical data and biospecimens.Serve as an educational venue for investigators and patients with IBD.
22IBD Exchange Strategies Collect detailed clinical information on patients with IBD including treatment, exposures, complications, outcomes from prospectively followed cohorts of adults and children with IBD,Collect patient reported outcomes from prospectively followed cohorts of patients with IBDCreate a biosample repository containing blood, feces, urine, and tissue samples,Create a knowledge environment to include a data warehouse, specialty research cores, analytic tools, educational tools for scientists, and educational tools for patientsPromote novel research through a peer reviewed research grants program.
23Prospective Cohorts Biobanks Specialty Research Cores Data RepositoryAnalytic ToolsSpecialty Research CoresResearch Grants
24SHARE / VEO / Other HT Projects Year 4-5ExchangeStudy “y”Partners 2“PROTECT”SHARE / VEO / Other HT Projects“RISK”Exchange cohort“Microbiome”Substudy “x”Other CCFA studies“GeneticsInitiative”OSCCAR
25Spectrum of Initial IBDEX Cohorts Patient Reported OutcomesClinical Activity IndicesBiosamplesNewly diagnosed pediatric CDPartners 2RISK & VEONewly diagnosed pediatric UCProtect & VEOEstablished adult IBDPartners 2/ PCORIExchange Cohort & SHAREExchange Cohort, SHARE, MicrobiomeNewly diagnosed adult IBDOSCCAR, Partners 2PCORIExchange Cohort, OSCCAR & SHARECommunity based International Referral center based
26Data Warehouse and Learning Environment Ancillary study investigators use data and samplesIBDEX cohorts generate data and samplesIBD EX Knowledge CenterInvestigators funded by CCFA and Helmsley generate data and samplesAncillary study investigators generate new dataAll newly generated data remains linked to the samples that were used to generate the data