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Juvenile Diabetes Research Juvenile Diabetes Research Foundation InternationalFoundation International
Research Update
Dayton Coles
JDRF Central Pennsylvania ChapterJDRF Central Pennsylvania Chapter
May 16, 2007May 16, 2007
What we’ll talk aboutWhat we’ll talk about
JDRF Research FundingJDRF Research Funding Cure GoalsCure Goals RegenerationRegeneration Artificial PancreasArtificial Pancreas JDRF’s Research Focus: JDRF’s Research Focus:
TherapeuticsTherapeutics
My Connection to Type 1My Connection to Type 1
How Research Has Made a How Research Has Made a DifferenceDifference
People with type 1 are living longer People with type 1 are living longer than ever beforethan ever before
The risk of complications is The risk of complications is declining for type 1declining for type 1
Tight control of blood glucose is Tight control of blood glucose is more achievable than evermore achievable than ever
JDRF Research FundingJDRF Research Funding
FY2005FY2005 $98 Million$98 Million
FY2006FY2006 $122 Million $122 Million
FY2007FY2007 $140 Million (estimate)$140 Million (estimate)
JDRF Funded ResearchJDRF Funded Research(FY06)(FY06)
JDRF Funded ResearchJDRF Funded Research(FY06)(FY06)
AutoimmunityAutoimmunity $41 million$41 million ComplicationsComplications $26 million$26 million Islet ReplacementIslet Replacement
TransplantTransplant $21 million$21 million Cell SourcesCell Sources $20 million$20 million
RegenerationRegeneration $8 million$8 million Metabolic Metabolic
ControlControl $6 million$6 million
TOTAL:TOTAL: $122 million$122 million
AutoimmunityAutoimmunity $41 million$41 million ComplicationsComplications $26 million$26 million Islet ReplacementIslet Replacement
TransplantTransplant $21 million$21 million Cell SourcesCell Sources $20 million$20 million
RegenerationRegeneration $8 million$8 million Metabolic Metabolic
ControlControl $6 million$6 million
TOTAL:TOTAL: $122 million$122 million
JDRF’s Cure Goal PathwaysJDRF’s Cure Goal Pathways
Islet Cell ReplacementIslet Cell Replacement (Transplantation & Source)(Transplantation & Source)
Regeneration of Native Beta CellsRegeneration of Native Beta Cells Restoring Immune ToleranceRestoring Immune Tolerance ComplicationsComplications (Preventing & Treating)(Preventing & Treating) Metabolic ControlMetabolic Control (Continuous Glucose (Continuous Glucose
Monitoring, Artificial Pancreas)Monitoring, Artificial Pancreas)
Therapeutic StrategiesTherapeutic StrategiesDefeat
Autoimmunity
Regenerate
Beta cells
Replace
Restore Metabolic Control
Restore Beta Cell Function
Replacing Beta CellsReplacing Beta Cells
Precursors
Beta cells
Beta cells
Neogenesis Replication
Islets• Cadaver (ex-vivo expanded) • Stem cell-derived• Reprogrammed (liver, K cell)• Xeno (pig, fish)• Encapsulation
• Pancreas-derived• Reprogrammed
Defeat Autoimmunity
Restore Metabolic Control
Restore Beta Cell Function
Regeneration of Regeneration of Native Beta CellsNative Beta Cells
Can beta cell regeneration occur in Can beta cell regeneration occur in patients with long standing patients with long standing
diabetes?diabetes? Many long-standing diabetes patients
have detectable C-peptide Research shows islets can expand under
different circumstances, like pregnancy and significant weight gain
Animal experiments indicate life-long cell generation
Post-mortem exams have shown insulin-positive cells in islets in long-standing diabetes patients
Can beta cell regeneration occur Can beta cell regeneration occur in patients with long standing in patients with long standing
diabetes? diabetes? Beta cell regenerative capacity may remain
clinically masked by Poor glycemia control and/or other metabolic
factors Residual anti-beta cell specific autoimmunity
Increase by directing careful attention to: Glycemia and lipid control Efforts to control anti-beta cell autoimmunity Delivering factors thought to promote beta
cell proliferation or survival in vivo
NeogenesisNeogenesis
ReplicationReplication
Cell DeathCell Death
Beta Cell MassBeta Cell Mass
(New Beta Cell Generation from Precursors)
(Cell Division)
Exocrine Exocrine DuctDuct
Therapeutics: Metabolic Control Immune Tolerance
Regeneration
Artificial Pancreas ProgramArtificial Pancreas Program
A1Cs Are High Even for Children A1Cs Are High Even for Children with Highly Involved Parentswith Highly Involved Parents
A1C results for 563 respondents in CWD A1C results for 563 respondents in CWD surveysurvey
<6.5
6.6-7.0
7.1-8.0
8.1-9.0
>9.0
13%13%
15%15%
40%40%
24%24%
8%8%73% are above the ADA recommended goal and 90% are above the recommended AACE goal - and these are among the most committed patients and families in the world.
Tremendous PotentialTremendous PotentialArtificial pancreas technologies have the potential to revolutionize diabetes care
Prevent highs that lead to heart attacks, amputations, blindness
Prevent life threatening lows Improve quality of life Facilitate other cure goals (e.g.,
regeneration)
1717
Continuous Glucose MonitorContinuous Glucose MonitorLook at the Difference in 9 DaysLook at the Difference in 9 Days
With CGM Use, 26% More Time in Normal Glucose With CGM Use, 26% More Time in Normal Glucose RangeRange
Diabetes Care 29:44-50.
Continuous Glucose Sensor
Insulin Pump
Control - Algorithm
What is an Artificial What is an Artificial Pancreas?Pancreas?
APP Project Goals
Accelerate the availability of a first generation artificial pancreas
Ensure the artificial pancreas and its components are available to the majority of people with type 1
Ensure devices from multiple companies are approved and reimbursed, encouraging investment in next generation technologies
APP/CGM Trials StatusAPP/CGM Trials StatusTwo tracks currently funded: Two tracks currently funded: Track One: continuous glucose sensors Track Two: artificial pancreas
Will Examine:Will Examine: Patient outcomes, e.g. HbA1c,
hypoglycemia Economic benefits, e.g. fewer
hospitalizations Quality of Life Various subpopulations Possible health plan partners
JDRF ApproachJDRF Approach Patient focused, independent from industry Commission independent, empirical research
Assess patient outcomes from use of artificial pancreas technologies
Answer regulator and payer questions Engage with key decision makers
FDA – Critical Path Opportunity List Center for Medicare and Medicaid Services Congress Private insurers Physicians
Product Developmen
t
Studies and
Trials
Coverageand
Reimbursement
Health Care System
Acceptance
Patient Acceptance and Use
Steps to Widespread AvailabilitySteps to Widespread Availability
JDRF’s Research FocusJDRF’s Research Focus
“Proactively accelerate the discovery, development, and delivery of disease-modifying
therapeutics to better treat and cure type 1 diabetes and its
complications.”
JDRF StrategyJDRF Strategy
From Discovery to TherapiesFrom Discovery to Therapies
Exploratory Research
Discovery Research
Preclinical Research
Clinical Research Clinical Trials Regulatory
Launch/AccessClinical DevelopmentTranslational ResearchBasic Research
Outcome Studies
3rd Party Coverage
• Screening/ rational Screening/ rational drug designdrug design
• Lead optimizationLead optimization• Proof-of-concept Proof-of-concept
in animal modelsin animal models• Safety studiesSafety studies
• Target Target identification/videntification/validationalidation
• Pathway Pathway evaluationevaluation
• Insights to Insights to disease disease processprocess
• Human Human proof-of-proof-of-concept concept testingtesting
• Safety and efficacy studiesSafety and efficacy studies• Phases I, II, IIIPhases I, II, III
• AcademiaAcademia • AcademiaAcademia
• Industry Industry (limited)(limited)
• Academia Academia (evolving)(evolving)
• IndustryIndustry • IndustryIndustry
• Academia Academia (evolving)(evolving)
• IndustryIndustry
Recent DevelopmentsRecent Developments Islet Cell ReplacementIslet Cell Replacement
Industry partner differentiates Embryonic Stem Cells into insulin-producing cells
Harvard scientists find that Natural Killer (NK) cells, knocked-out under current immunosuppressive protocols, may actually reduce the chance that transplanted tissue will be rejected
JDRF-funded researchers in San Diego have discovered that non-secreting tissue in the pancreas can be transformed into insulin-producing cells.
Xenotransplantation: Trials launched and FDA discussions have been initiated
Cadaver Islet Transplantation: Grant activated
Recent DevelopmentsRecent Developments
Regeneration of Native Beta CellsRegeneration of Native Beta Cells
JDRF-funded researchers at the University of Massachusetts have identified a protein in beta cells that regulates the production of insulin.
New RFA launched on physiologic beta cell regeneration
Academic R&D grants under development with Broad, Harvard, Stanford, etc
GLP-1/Gastrin preclinical studies completed and trial has launched
Insulin-Making Protein identified in Beta Cells
Recent DevelopmentsRecent Developments Restoring Immune ToleranceRestoring Immune Tolerance
Discovery that single protein can switch a key component of the immune system on or off depending on which molecule it teams with, sheds light on what is involved in keeping the immune system in check, paving the way for researchers to develop therapies for type 1 diabetes and other autoimmune afflictions such as arthritis and allergies
Using natural compounds derived from a shrub and the venom of a sea anemone, JDRF-funded researchers at the University of California-Irvine thwarted the autoimmune attack causing type 1 diabetes in experiments with human cells and animals.
Rituxan trial launched, ATG trial to launch, IL1RA and AAT trials in development
Innate Immunity Program launched Resource creation: Network for Pancreatic Organ donors with Diabetes to
launch
Recent DevelopmentsRecent Developments ComplicationsComplications
JDRF-funded researchers have identified a potential mechanism that may shed light on why some people with diabetes lose the ability to recognize and correct hypoglycemia
A JDRF-funded research project at Columbia University Medical Center that goes back 16 years has taken a major step toward translation into therapies to treat diabetic complications.
Dr. Lloyd Aiello of the Joslin Diabetes Center has shown that the compound ruboxistaurin slowed the progress of retinopathy by inhibiting an enzyme in the body called protein kinase C beta (PKC beta), which is believed to contribute to the blood vessel damage that leads to the disease. This is the first time a drug has been shown to protect against the complication in a human clinical trial.
Recent DevelopmentsRecent Developments Metabolic ControlMetabolic Control
JDRF CGM Clinical Trial launched with enrollment initiated January
Funded six site Artificial Pancreas Project Consortium JDRF-FDA dialogue:
Resulted in removal of Investigational Device Exemption – saving considerable time and resources
“Critical Path” Initiative February meeting began to define pathway and approval metrics
What You Can DoWhat You Can Do
Pay attentionPay attention Time and TreasureTime and Treasure Advocate – NIH funding and APPAdvocate – NIH funding and APP Clinical TrialsClinical Trials OtherOther
QuestionsQuestions