DETECTION & DIAGNOSIS

DIABETES

ISLT-BDX ISLET BETA-CELL ASSAY

Current diagnostic tools for diabetes mellitus are only effective in patients who have already suffered the destruction of a large fraction of insulin-producing cells in the pancreas, called beta cells. These tests measure impairment in functional responses to food stimuli, as exemplified by a glucose tolerance test. As a result, these diagnostics are limited in that they can only identify cell destruction when these pancreatic pancreatic beta cells are already largely eradicated, leaving clinicians with only few opportunities for intervention.

ISLT-Bdx employs a novel droplet digital PCR (ddPCR) technology, on which Islet Sciences recently published a paper, that demonstrates superior efficacy in improved detection of beta-cell loss, a key biomarker of diabetes progression.

Current diagnostic tools for diabetes mellitus are only effective in patients who have already suffered the destruction of a large fraction of insulin-producing cells. These tests measure impairment in functional responses to food stimuli, as exemplified by a glucose tolerance test. As a result, these diagnostics have the significant weakness that they can only identify cell destruction when the pancreatic islets of Langerhans are already largely eradicated, leaving clinicians with few opportunities for intervention.

Yale scientists, under the direction of Professor Kevan Herold, have identified a biomarker for ongoing cell death, and developed a non-invasive diagnostic test that can detect cell loss in vivo earlier than current functional tests.

DNA sequences from the INS gene were discovered to be specifically hypomethylated in human cells, as were sequences from the Ins1 gene in murine cells. As these cells are lost during the development of diabetes, some of their genomic DNA is released into the serum. The Herold group new assay measures the level of circulating cell-specific genomic DNA by making use of methylation-sensitive quantitative PCR specific for the hypomethylated insulin gene sequences. This level of circulating hypomethylated DNA is significantly increased in human patients with new-onset diabetes, and rises above background before the presentation of functional diabetes.

This assay can potentially be used to determine the progression of disease and guide its treatment in diabetic patients, as well as the prognosis of islet or pancreas graft recipients. Importantly, it could also be used to guide prevention therapy in patients who do not yet have overt diabetes.

Yale scientists, under the direction of Professor Kevan Herold, have identified a biomarker for ongoing cell death, and developed a non-invasive diagnostic test that can detect cell loss in vivo earlier than current functional tests.

This invention establishes a novel tool that can diagnose the development of diabetes before the presentation of hyperglycemia and can do so earlier than current methods. The technique relies on a minimally invasive test of patient blood and can be done in a regular laboratory setting in a relatively short time and with low cost.

Yale scientists, under the direction of Professor Kevan Herold, have identified a biomarker for ongoing cell death, and developed a non-invasive diagnostic test that can detect cell loss in vivo earlier than current functional tests.

Akirav et al. Detection of cell death in diabetes using differentially methylated circulating DNA. Proc Natl Acad Sci U S A. 2011 Nov 22;108(47):19018-23.

Usmani-Brown et al. Analysis of beta-cell death in Type 1 diabetes by droplet digital PCR. Endocrinology 2014 Jul 8; ahead of print: http://dx.doi.org/10.1210/en.2014-1150

ISLET SCIENCES
INITIAL TARGET
PATIENTS -SUMMARY

  • Initially targeting end-stage renal disease (ESRD)
    1. Diabetes is leading cause of ESRD
      Causes 44% of new ESRD cases
  • 100,000 new cases of ESRD reported annually
  • 20-40% of Type 1 diabetics develop ESRD by age 50
    1. IN THE ABSENCE OF ADEQUATE TREATMENT BY DIALYSIS OR TRANSPLANTATION, THESE PATIENTS DIE
  • 1,000,000 people living with kidney transplant and diabetes