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Prevention of t1d

Prevention of t1d. Jessica Dunne, PhD, Director, Discovery Research. Protecting Future Generations From T1D. Prevention is as Important as a Cure. D ramatic rise especially among young children

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Prevention of t1d

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  1. Prevention of t1d Jessica Dunne, PhD, Director, Discovery Research

  2. Protecting Future Generations From T1D Prevention is as Important as a Cure • Dramatic rise especially among young children • Children born to a family with a close relative who has T1D have a greater risk of developing the disease • Only prevention can alter this trend and protect future generations from T1D 2

  3. Cases/100,000/yr in Children 0–14 yr Incidence and Prevalence of T1D Increasing and Occurring at Earlier Age 3

  4. Projected Number of Youth < 20 Years With T1D: Increased Incidence Scenario • Number of US youth with T1D projected to increase 3.3-fold by 2050 • Highest among NHW youth (7.04/1000 in 2050) • Largest relative increase among Hispanic youth (6.6-fold increase) • US health care systems need to be prepared All NHW Hispanic AA Imperatore, et al. Diabetes Care, 35(12), 2515, 2012

  5. T1D Natural History: A Framework for Prevention • Risk of developing T1D can be identified • T1D develops with a relatively predictable course with variable rate of progression • Interventions can be developed to arrest progression Adapted from Eisenbarth GeneticRisk Environmental Etiologies Beta Cell Autoimmunity Beta Cell Loss 100% Glucose Intolerance Clinical Symptoms Functional Beta Cell Mass RecentOnset At Risk Pre-Symptomatic Established Diabetes 0% Time 5

  6. Risk of T1D in relatives of individuals with T1D • Identical Twin: 30-70% • Multiple Affected First Degree Relatives: 20-50% • Sibling: 8% (but if HLA risk genes identical:30-70%) • Offspring • Father: 5% • Mother: 3% • If no Family Hx- General Population: 0.4% (but if HLA risk genes: 4%) (Only 10-15% of newly diagnosed cases of T1D have a relative with T1D) 6

  7. ? Enteroviruses • The most common viruses in man; frequent infection in early childhood • Cause both mild and severe infections, such as • meningitis, encephalitis, paralysis (poliomyelitis) • myocarditis, chronic cardiomyopathies • pancreatitis, hand foot and mouth disease • More than 100 different types • Vaccine has been developed against one enterovirus group (polioviruses) 7

  8. Enteroviruses and Type 1 Diabetes • Islet cell damage in fatal enterovirus infections • Enterovirus detection in new onset T1D pancreas (nPOD-V, DiViD) • T1D Genetics: IFIH1 gene affects response to enterovirus • Viral infection (type 1 interferon) signature pattern detected prior to onset of T1D autoimmunity • Viral antibodies first detected around time of T1D autoimmunity 8

  9. The Hygiene Hypothesis • Lack of early childhood exposure to infectious agents, symbiotic microorganisms (e.g., gut flora), and parasites increases susceptibility to T1D by suppressing natural development of the immune system. 9

  10. The Gut Microbiome in T1D • Metabolism • Synthesis of vitamins • Digestion of harmful compounds • Energy production • Fermentation of non-digestibile substances • Protection • Stimulation of immune system • Antimicrobial effect • Physical barrier against pathogenic bacteria 10

  11. JDRF Gut Microbiome Program Key Messages • JDRF is supporting several promising vaccine projects, including vaccines to induce normal micro-organisms in the GI tract • The JDRF Microbiome Consortium was created in 2011 to engage the community, create collaborations and drive the field forward • Important JDRF Microbiome Consortium findings: • The gut microbiome is fairly stable after the age of 3 • The gut microbiome differs in children who go on to develop T1D from those that don’t • There is some evidence that this change precedes the onset of autoimmunity • The gut microbiome has small ecosystems or networks and the interactions between these networks is important in determining function • The gut microbiome changes with age, diet, vitamins, antibiotic use, etc., and laying down an early foundation may be important 11

  12. THANK YOU

  13. Encapsulated cell replacement therapy Albert Hwa, PhD, Director, Discovery Science

  14. Pancreas and Islet Transplant Can “Cure” T1D • “Cures” Type 1 Diabetes • Limited by supply of healthy donor islets, pancreases • Long term use of powerful immunosuppressive drugs

  15. Encapsulated Cell Replacement Therapy • Beta Cell Source • Replenishable • Appropriately functional • Scalable, consistent production • Encapsulation System • Prevents immune rejection • Supports long term cell survival and function • Allows appropriate insulin kinetics

  16. JDRF Encapsulation Program Goals • Purpose To support the development of implantable encapsulated beta cell products to safely provide normal glucose control to individuals living with T1D • Ultimate Goal Implantable, replenishable beta cell products with encapsulation technology and no immunosuppression, capable of delivering insulin independence

  17. JDRF Encapsulation Consortium Novel Biomaterials JDRF Macro Device Designs Local Immunosuppression Late-stage Studies • MIT/Univ. Mass./Harvard/Joslin • Kings College (UK) • Northwestern Univ. • Georgia Tech Univ. • U. Alberta (CA) • Emory Univ. • Data & protocol sharing • Cross-team comparisons • Standardization • Core facilities • Univ. Miami/DRI • Brighams & Womens Hosp. • Univ. Albeta (CA) • Univ. Twente (NL) • Univ. Cal. San Francisco • Univ. British Columbia (CA) • Beta-O2 • Mass General Hospital • Univ. Minnesota • Emory Univ. • Univ. Alberta (CA) • Univ. Illinois Chicago • Mass. General Hospital • Northwestern Univ. • Georgia Tech Univ. • Univ. British Columbia (CA) • Univ. Louisville • U. Miami/DRI Standardization Tools • Univ. California Irvine • Vrije Univ. (BE)

  18. Beta O2 - ßAir device • Pilot trial showed long-term cell function and survival; decrease in HbA1c • Follow up trial with 8 patients

  19. Living Cell Technologies – encapsulated pig islets • High health status pigs • No xeno-relevant viruses, bacteria and parasites. • Herd now bred in documented bio-isolation. • Three year health records and regular monitoring. • Alginate-based microcapsules • JDRF sponsored part of New Zealand clinical trial, as approved by the NZ regulatory authority Auckland Islands, New Zealand. Living Cell Technologies, Ltd.

  20. Comments and Questions

  21. THANK YOU

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