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Developing a small peptide to control autoimmune inflammation in type diabetes

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI131784-01
Agency Tracking Number: R41AI131784
Amount: $297,387.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA16-303
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-02-15
Award End Date (Contract End Date): 2018-12-19
Small Business Information
3000 E 7TH AVENUE PKWY
Denver, CO 80206-3961
United States
DUNS: 016344134
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 DAVID WAGNER
 (303) 929-7865
 david.wagner@ucdenver.edu
Business Contact
 DAVID WAGNER
Phone: (303) 929-7865
Email: david.wagner@ucdenver.edu
Research Institution
 UNIVERSITY OF COLORADO DENVER/HSC DENVER
 
13001 E 17TH PLACE, ROOM W1126
AURORA, CO 80045-2570
United States

 Nonprofit college or university
Abstract

Abstract Type Diabetes T D affects an ever growing population While this disease
typically has been associated with juveniles the disease in adult populations is rapidly
increasing The defining clinical component is insulin loss which occurs because of sustained
inflammation in the islets At present there is no means to prevent or reverse insulin loss A
major inflammatory pathway in T D that contributes to insulin loss is the CD CD dyad
CD is expressed on a wide array of cells and when engaged by CD creates localized
inflammation This pathway is decisive in T D blocking the interaction prevents diabetes onset
and reverses hyperglycemia in new onset diabetic mice A major impediment to drug
development in diabetes has been the failure of therapeutics to translate from mouse to human
Mindful of this we discovered that CD provides a link between mouse and human during
T D We discovered that NOD mice the industry standard model for T D increase CD
expression including on a sub population of T cells during diabetes development Those cells
termed Th not only expand in number as diabetes develops but Th cells are singularly
capable of transferring T D to scid recipients In a translational approach we discovered that
Th cells become prominent in human T D patients regardless of the age HLA haplotype
auto antibody status or duration of disease Like in the mouse model Th cells start at low
percentages but increase as human subjects progress to T D and remain at high levels even up
to years after diagnosis New onset as well as long term diabetic patients have highly
expanded numbers of Th cells when compared to non autoimmune or type diabetic
controls A portion of TrialNet defined Pre T D subjects also have expanded Th cell numbers
suggesting that these cells become pathogenic over time depending upon CD expression
Controlling CD therefore will be therapeutically advantageous Methods to control CD have
relied upon monoclonal antibodies or randomly generated small organic molecules Both those
options have failed clinically To address this we developed a series of peptides derived from
the CD protein sequence that are designed to target CD binding sites These peptides do
not function like antibodies and unlike the random generated organic molecule approach have
high specificity for CD In preliminary work we determined that some of the peptides prevent
diabetes onset in NOD mice and one of the peptides thus far reversed hyperglycemia in new
onset diabetic mice The goals of this grant are to establish clinical parameters that will allow
further development of a lead candidate for therapeutic development We propose to determine
how candidate peptides impact glucose tolerance testing serum insulin levels and c peptide
levels Methods to control CD CD interaction have failed because heretofore they have depended upon
monoclonal antibody or randomly generated organic molecules We designed CD targeting peptides
that prevent diabetes onset and reverse hyperglycemia in new onset diabetic mice

* Information listed above is at the time of submission. *

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