Development of T-cell receptor repertoire profiling as a diagnostic for T1D

Information

  • Research Project
  • 7998971
  • ApplicationId
    7998971
  • Core Project Number
    R43DK089783
  • Full Project Number
    1R43DK089783-01
  • Serial Number
    89783
  • FOA Number
    PA-08-114
  • Sub Project Id
  • Project Start Date
    8/1/2010 - 14 years ago
  • Project End Date
    7/31/2012 - 12 years ago
  • Program Officer Name
    ARREAZA-RUBIN, GUILLERMO
  • Budget Start Date
    8/1/2010 - 14 years ago
  • Budget End Date
    7/31/2011 - 13 years ago
  • Fiscal Year
    2010
  • Support Year
    1
  • Suffix
  • Award Notice Date
    7/27/2010 - 14 years ago

Development of T-cell receptor repertoire profiling as a diagnostic for T1D

DESCRIPTION (provided by applicant): The goal of this Phase I project is the identification of a molecular signature in the T-cell receptor repertoire of early-stage Type 1 Diabetes (T1D) patients that distinguishes these patients from controls. At present, immunomodulatory therapies have not proven useful for treatment of T1D, largely because of adverse side effects and also because pancreatic function has already been compromised by the time symptoms present. A diagnostic product that could detect the very earliest events in breaking tolerance, such as the development of a signature pattern in the repertoire of T-cell receptor (TCR) sequences, would allow for early intervention in high-risk individuals, potentially providing an opportunity for preservation of islet cell function and natural insulin production. Herein, we propose to commercialize our high-throughput TCR( sequencing assay to identify signals in the TCR( sequence repertoire that are indicative of loss of islet cell function. The ability to simultaneously sequence millions of individual T-cell receptor genes in single individuals provides, for the first time, the potential to directly observe disease-associated changes in the immune repertoire, the very set of receptors that evolves as T1D moves from initiation to progressive beta cell destruction. The utility of this signature as a diagnostic tool could expand treatment options for T1D by identifying individuals in the very earliest stages of disease, when therapy and treatment could be most effective. PUBLIC HEALTH RELEVANCE: Type 1 Diabetes (T1D) is usually diagnosed when symptoms present, a stage of disease in which autoimmunity has caused the loss of islet cell function. We propose to identify a signature pattern in the repertoire of T-cell receptor (TCR) sequences that could serve as a diagnostic product to detect the very earliest stage of disease. A diagnosis at earlier stages would allow for early intervention in high-risk individuals, potentially providing an opportunity for preservation of islet cell function and natural insulin production.

IC Name
NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • Activity
    R43
  • Administering IC
    DK
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    332770
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    847
  • Ed Inst. Type
  • Funding ICs
    NIDDK:332770\
  • Funding Mechanism
    SBIR-STTR
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    ADAPTIVE BIOTECHNOLOGIES CORPORATION
  • Organization Department
  • Organization DUNS
    832591544
  • Organization City
    SEATTLE
  • Organization State
    WA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    981027402
  • Organization District
    UNITED STATES