1Type 1 Diabetes:Progress Toward its Prevention,Treatment, and CureJulia GreensteinJDRF VP Cure therapiesjgreenstein@JDRF....
JDRF Mission: Cure, Treat, and Prevent T1DCure T1D by removing thedisease from the lives of ourloved onesCureCureBetter wa...
3Our Goal: Life Changing Therapies…Leading to a World Without T1DClinicalDevelopmentRegulatoryADVOCACYRESEARCHADVOCACYRESE...
JDRF Partners4 Proactively accelerate the discovery, development, anddelivery of drugs and devices to cure, better treat,...
JDRF Mission: Cure, Treat, and Prevent T1DCure T1D by removing thedisease from the lives of ourloved onesCureCureBetter wa...
Cadaver Islet TransplantationLimitations•Islet source•ImmunosuppressionSuccess•50–60% 5-yr insulin independence;•80–90% re...
Human Embryonic Stem Cell-Derived IsletSources: Progenitors Mature to Islets In-Vivo
• Physical barrier to protect islets from immune responses• Barrier should allow islets to survive and function, sensing g...
Diabetes 50:2020 (2010)In this individual, after more than 50 years of type 1 diabetes,•every islet had at least one insul...
Beta Cell Regenerating TherapySurvivalSurvivalReplicationReplicationNeogenesisNeogenesisProgenitorcellDe-differentiatedbet...
JDRF Mission: Cure, Treat, and Prevent T1DCure T1D by removing thedisease from the lives of ourloved onesCureCureBetter wa...
120102030405060701950 1960 1970 1980 1990 2000FinlandSwedenColoradoGermanyCases/100,000/yrin children 0-14 yrsT1D Incidenc...
Relative Percent Increase ofType 1 Diabetes Incidence inFinland 1965-1996 (32 yrs)Type 1 Diabetes is Occurring Earlier in ...
14Rationale for T1D Prevention Risk of developing T1D canbe diagnosed T1D develops with a relativelypredictable course w...
15T1D Prevention InterventionsAdapted from Eisenbarth100%0%FunctionalBetaCellMassAt Risk Pre-DiabetesRecentOnset Establish...
16Approaches to Prevent T1D Primary PreventionViral vaccines: Enteroviral vaccineMicrobiota-induced immunoregulation re...
JDRF Mission: Cure, Treat, and Prevent T1DCure T1D by removing thedisease from the lives of ourloved onesCureCureBetter wa...
MeanHbA1c 2011-2012 data 67 Clinics n = 24,116Poor Glucose Control in T1D in USADespite Care at State-of-the-Art Clinic...
19Closed Loop Artificial Pancreas Systems:Simulate a normal pancreas• Requires:- Improved glucose sensors- Improved Insuli...
2011Very Low GlucoseInsulin Off PumpPump Shuts offwhen user notresponding tolow-glucose alarm22HypoglycemiaMinimizerPredic...
Overnight Closed-Loop Control will be Early Successand Important (55-75% of Severe Hypoglycemia at Night)• Lowers glucose ...
22Thank you!
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  • T1D onset with loss of ~ 70% fx beta cells 70% anatomc loss Insulitisi in 20% of remaining islets with beta cells Can see non inflamed islets lobuar Resiudal explains honeomone oeriod Envirn stimuli—first year of life and second year T1D assoc autoab s—insulin, GAD, IA-2 Znt8--- insulin proisnusl targted in young Single autoab –less than 5% progress—autoimm is not autoimm disesase----progress Only a fraction progress forward With loss of fx betaq cell mass---18 mnths a dx—see decreased beta cell glucsoe sensitivity –ability to recognize and response to a glucose load with insulin secretion; HbA1c rising abn IVGTT OGTT Handling of insulin Heterogeneity Asyx T1D
  • Julia Greenstein, Ph.D.

    1. 1. 1Type 1 Diabetes:Progress Toward its Prevention,Treatment, and CureJulia GreensteinJDRF VP Cure therapiesjgreenstein@JDRF.orgApril 9, 2013
    2. 2. JDRF Mission: Cure, Treat, and Prevent T1DCure T1D by removing thedisease from the lives of ourloved onesCureCureBetter ways to Treat T1D sopeople can live healthierlives more convenientlyTreatTreatPrevent T1D from occurring& stopping it earlyPrevent
    3. 3. 3Our Goal: Life Changing Therapies…Leading to a World Without T1DClinicalDevelopmentRegulatoryADVOCACYRESEARCHADVOCACYRESEARCHADVOCACYRESEARCHDeliveryto PatientsDiscoveryResearch Proactively accelerate the discovery, development, anddelivery of drugs and devices to cure, better treat, andprevent type 1 diabetes and its complications.
    4. 4. JDRF Partners4 Proactively accelerate the discovery, development, anddelivery of drugs and devices to cure, better treat, andprevent type 1 diabetes and its complications.
    5. 5. JDRF Mission: Cure, Treat, and Prevent T1DCure T1D by removing thedisease from the lives of ourloved onesCureCureBetter ways to Treat T1D sopeople can live healthierlives more convenientlyTreatTreatPrevent T1D from occurring& stopping it earlyPrevent
    6. 6. Cadaver Islet TransplantationLimitations•Islet source•ImmunosuppressionSuccess•50–60% 5-yr insulin independence;•80–90% reversal of hypoglycemiaunawareness
    7. 7. Human Embryonic Stem Cell-Derived IsletSources: Progenitors Mature to Islets In-Vivo
    8. 8. • Physical barrier to protect islets from immune responses• Barrier should allow islets to survive and function, sensing glucoseand releasing insulin physiologicallyDr. Tejal A. Desai UCSFEncapsulation of Islet or Islet Precursor forImmunoisolation
    9. 9. Diabetes 50:2020 (2010)In this individual, after more than 50 years of type 1 diabetes,•every islet had at least one insulin positive beta cell (left)•replicating beta cells cells were also found (right)After 50 years of type 1 diabetes, beta cells canstill be present
    10. 10. Beta Cell Regenerating TherapySurvivalSurvivalReplicationReplicationNeogenesisNeogenesisProgenitorcellDe-differentiatedbeta cellAlpha cellReprogramming-TransdifferentiationRedifferentiationDifferentiation
    11. 11. JDRF Mission: Cure, Treat, and Prevent T1DCure T1D by removing thedisease from the lives of ourloved onesCureCureBetter ways to Treat T1D sopeople can live healthierlives more convenientlyTreatTreatPrevent T1D from occurring& stopping it earlyPrevent
    12. 12. 120102030405060701950 1960 1970 1980 1990 2000FinlandSwedenColoradoGermanyCases/100,000/yrin children 0-14 yrsT1D Incidence (# new cases/yr) is doublingevery 20 yrs (~3-4% annual increase)Burden: Increasing Incidence of T1D
    13. 13. Relative Percent Increase ofType 1 Diabetes Incidence inFinland 1965-1996 (32 yrs)Type 1 Diabetes is Occurring Earlier in LifeProjected Age-Incidence of T1Dfrom 2006-2020 in FinlandLancet: 371:1777, 2008
    14. 14. 14Rationale for T1D Prevention Risk of developing T1D canbe diagnosed T1D develops with a relativelypredictable course withvariable rate of progression Rate of progression to insulindependence can be predictedAdapted from Eisenbarth100%0%FunctionalBetaCellMassAt Risk Pre-DiabetesRecentOnset Established DiabetesDiagnosisTimeGeneticRisk +EnvironmentalEtiologiesBeta CellAutoimmunityBeta CellLossGlucoseIntoleranceInsulinDependence
    15. 15. 15T1D Prevention InterventionsAdapted from Eisenbarth100%0%FunctionalBetaCellMassAt Risk Pre-DiabetesRecentOnset Established DiabetesDiagnosisTimeBeta CellAutoimmunityBeta CellLossGlucoseIntoleranceInsulinInsulinDependencePrimaryPreventionSecondaryPreventionGeneticRisk +EnvironmentalEtiologies
    16. 16. 16Approaches to Prevent T1D Primary PreventionViral vaccines: Enteroviral vaccineMicrobiota-induced immunoregulation related“vaccines”Beta cell autoantigen tolerogenic vaccines Secondary PreventionBeta cell autoantigen tolerogenic vaccinesBeta cell survival agents
    17. 17. JDRF Mission: Cure, Treat, and Prevent T1DCure T1D by removing thedisease from the lives of ourloved onesCureCureBetter ways to Treat T1D sopeople can live healthierlives more convenientlyTreatTreatPrevent T1D from occurring& stopping it earlyPrevent
    18. 18. MeanHbA1c 2011-2012 data 67 Clinics n = 24,116Poor Glucose Control in T1D in USADespite Care at State-of-the-Art Clinics(HbA1c should be <7.0% to avoid complications)Goal: HbA1C <7.5% Goal: HbA1C <7%18
    19. 19. 19Closed Loop Artificial Pancreas Systems:Simulate a normal pancreas• Requires:- Improved glucose sensors- Improved Insulins + otherdrugs (glucagon)- Improved control software- Dual/multi-chamber pumps
    20. 20. 2011Very Low GlucoseInsulin Off PumpPump Shuts offwhen user notresponding tolow-glucose alarm22HypoglycemiaMinimizerPredictivehypoglycemiacauses alarmsfollowed byreduction orcessation ofinsulin deliverybefore someonegets low33Hypoglycemia/HyperglycemiaMinimizerSame as Product#2 but addedfeature allowinginsulin dosingabove highthreshold(e.g., 200mg/dl)44AutomatedBasal/HybridClosed LoopClosed loop atall times withmeal-time manualassist bolusing55Fully AutomatedInsulin ClosedLoopManual meal-time boluseliminated66Fully AutomatedMulti-HormoneClosed LoopFirstGenerationSecondGenerationThirdGenerationProgression to Artificial Pancreas SystemsThere Will Be Multiple Generations: Each Becoming More Automatic
    21. 21. Overnight Closed-Loop Control will be Early Successand Important (55-75% of Severe Hypoglycemia at Night)• Lowers glucose variability• Controls to a tight range (71% vs 43% in range)• Reduces extreme hyperglycemia andhypoglycemia (2.1% vs 4.1% <70mg/dl).
    22. 22. 22Thank you!

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