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Measurement of Beta Cell Death in Diabetes

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R42DK095639-02
Agency Tracking Number: R42DK095639
Amount: $1,348,103.00
Phase: Phase II
Program: STTR
Solicitation Topic Code: 200
Solicitation Number: PA13-235
Solicitation Year: 2014
Award Year: 2014
Award Start Date (Proposal Award Date): 2014-09-01
Award End Date (Contract End Date): 2016-08-30
Small Business Information
BOX 8175
New Haven, CT 06530-0175
United States
DUNS: 142406110
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (203) 785-6507
Business Contact
Phone: (203) 393-9439
Research Institution
NEW HAVEN, CT 06520-8327
United States

 Nonprofit College or University

DESCRIPTION provided by applicant All forms of diabetes are characterized by the death of insulin producing cells In Type diabetes T D this leads to the reliance on exogenous insulin for survival Death of cells is silent it cannot be detected in vivo until it has progressed to such an extent that metabolic function is impaired The loss of cells has only been assessed by functional studies that can be affected by environmental factors New therapies have been developed that can modulate the course of T D but the effective application of these therapies requires a clearer understanding of the pathologic processes including the timing and precipitants of cell death To directly measure cell death in vivo in
our Phase I STTR we developed an assay using a novel droplet digital PCR ddPCR that detects INS DNA derived from cells The release of INS DNA with epigenetic modifications unmethylated CpGs identifies the cellular source of the DNA The assay can detect unmethylated DNA between a range of approximately copies l to copies l with a linear regression for the log transformed copy number of In our studies we showed that the assay could distinguish individuals with T D from healthy control subjects and normoglycemic individuals who are at risk for T D and who progress to disease from healthy control subjects We conclude that ddPCR is a useful method to detect cell death and is more sensitive and feasible than other methods such as nested PCR In Phase II we will address critical issues in assay development such as its ability to predict metabolic failure and remission The goal of the Phase II is analyze the diagnostic potential and improve the prognostic accuracy of our assay in diverse clinical settings We plan to study individuals at risk for development of T D patients with new onset T D who enter clinical remissions and exacerbations patients with cystic fibrosis related diabetes and recipients of islet autotransplants in which cell destruction is thought to occur We will combine the results from this assay with other data and perform statistical analyses using a logistic regression approach to identify variables that predict beta cell death and modifiers of the measurement The goal of this Phase II STTR is to obtain the data needed to commercialize this method as a diagnostic assay for monitoring at risk patients and those with established T D who may be treated with immune modulators or islet transplants and patients with other forms of diabetes Our goal is to perform studies that will support the utility of this approach as a biomarker of cell death in patients with and at risk fo diabetes Future studies will involve expanded study groups such as Type diabetes PUBLIC HEALTH RELEVANCE All forms of diabetes involve death of cells We have developed a droplet digital PCR assay to measure cell death in vivo We propose to apply this new assay to various clinical setting in order to determine the diagnostic value of our assay

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

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