Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Gene-Specific Models and Therapies for Type 1 Diabetes

1,727 views

Published on

We like to think of type 1 diabetes as a disease that has one all-encompassing cure, but because multiple genetic factors can contribute to disease susceptibility, it is likely to be more involved than just one simple fix. As researchers studying the disease, we have been limited to using a model with one genetic profile - the non-obese diabetic (NOD) mouse. This model doesn’t represent the genetic diversity of children and adults with type 1 diabetes. Development of a suite of mice that express human diabetes-relevant gene variants in various combinations will allow scientists to develop therapies for specific genetics. In this way, we will be better suited to find the necessary cures for different genetic profiles that make up the disease collectively called type 1 diabetes.

Published in: Science
  • Be the first to comment

Gene-Specific Models and Therapies for Type 1 Diabetes

  1. 1. Gene-Specific Models and Therapies for Type 1 Diabetes Jeremy J. Racine
  2. 2. 2 Multiple different genetic profiles can lead to type 1 diabetes in children Most potential therapies are designed in the NOD mouse, which is a single genetic profile. The Problem
  3. 3. 3 Class IClass I The NOD Mouse The First Generation Trait-Specific Model β2m Human Class I No cell surface mouse Class I Model Carries Specific Genetic Variant of HLA Class I found in Diabetic Children Genetic Removal of β2m
  4. 4. 4 Class IClass I The NOD Mouse The First Generation Trait-Specific Model β2m Human Class I No cell surface mouse Class I - Cannot test antibody-based therapies - Difficulty determining autoantibody status prior to treatment for “at-risk” classification.
  5. 5. 5 Class IClass I The NOD Mouse I have recently directly removed both of the mouse versions of the HLA Class I genes and am currently introducing the available human Class I variants linked to diabetes in children into this model to replace the first generation model. Generating a Next Generation “Blank Slate” Model
  6. 6. 6 Class IClass I Class II Generating a Next Generation “Blank Slate” Model The NOD Mouse The NOD Class II gene needs to be removed in order to combine human HLA Class II gene variants linked to diabetes in children to the multiple HLA Class I variants identified.
  7. 7. 7 HLA Class I “presenting” target for immune cells. Generating a Peptide- “Vaccination-Like” Therapy for Genetic Variation HLA-A2.1 Target Immune Cell Insulin producing cell.
  8. 8. 8 Immune Cell Can we use a vaccine to block? STOP Generating a Peptide- “Vaccination-Like” Therapy for Genetic Variation HLA-A2.1
  9. 9. 9 4 targets have been identified using first generation model and confirmed in patients. Attach targets to a “microsphere” made from a material already in-use in the clinic. Generating a Peptide- “Vaccination-Like” Therapy for Genetic Variation HLA-A2.1
  10. 10. 10 Immune Cell “Vaccine” seems to reprogram immune cells. We need to learn how. Generating a Peptide- “Vaccination-Like” Therapy for Genetic Variation HLA-A2.1
  11. 11. 11 Trait Specific Mouse Model Trait Specific Therapy Trait Specific Mouse Model Trait Specific Therapy TraitSpecific Mouse Model TraitSpecific Therapy TraitSpecific Mouse Model TraitSpecific Therapy The Ultimate Goal of My Career
  12. 12. Thank You For Your Support

×