*EUSTACHE PARAMITHIOTIS

Development of biomarkers for measurement of early stage diabetes disease and for prediction of response to therapy

Competition: FOCUS Program 2009
Funding: $2,360,000 / 3 years 
Beginning: September 2014

(COMPLETED PROJECT)

Relying on Caprion’s CellCarta proteomics technology to develop panels of protein diabetes biomarkers, this project will improve early diagnosis and monitor disease progression, as well as, evaluate therapeutic response.

Overview

A unique panel of clinically validated pancreatic ß-cell biomarkers readily detected in blood were discovered which serve to rapidly identify early pre-diabetic subjects and follow their disease progression. Treating this group early has the best chance to impact subjects with this long-term
debilitating disease.

This ambitious project, conducted by Dr. Paramithiotis, has 2 specific objectives: i) to identify and validate protein biomarker candidates associated with the mass and the functional state of pancreatic beta-cells, which play a critical role in the development of type 2 diabetes, and ii) to identify and complete early stage evaluation of protein biomarker candidates that can be used to monitor type 2 diabetes treatment efficacy. Using Caprion’s CellCarta proteomic platform, the team conducted an extensive analysis of pancreatic proteins secreted normally and under disease conditions from humans and several animal models of diabetes. Using three different experimental models (mouse and rat beta cell lines and human pancreatic islets), the team identified a promising dataset of candidate biomarkers for both beta cell mass and function. The proteins identified were grouped as a network and the main pathways found are derived from i) mechanisms of secretion, ii) lipid metabolism, and iii) carbohydrate metabolism. “The set of biomarkers identified during the discovery phase is impressive. All the assays we are currently developing could become the basis of diagnostic tests to monitor pre-diabetes, enable targeted therapies, and monitor beta-cell status in transplant patients,” declares Dr. Eustache Paramithiotis. The biomarkers are currently being validated in humans as well as diabetes animal models.

Impact on the drug discovery process

  • Allows for rapid identification of pre-diabetic subjects for clinical trials:
    Targets group with best potential for successful treatment of diabetes
    Enables novel therapeutic approaches to diabetes (such as islet transplantation) currently hampered by lack
    of useful and sensitive biomarkers
  • Unique opportunity to directly follow the decline of ß-cell function in subjects leading to the de velopment of novel
    early-stage diabetic therapies.

Key facts

  • Diabetes affects 25.8 million people worldwide.
  • In the US alone, 80 million people (25%) over the age of 20 are pre-diabetic.
  • If diagnosed early at the pre-diabetes stage, disease progression can be arrested or even prevented.
  • Diabetes is a major risk factor for many diseases such heart disease, renal insufficiency, and stroke.

Main accomplishments

  • Panel of 30 ß-cell biomarkers are readily detected in plasma that segregate diabetes into stages of disease with excellent individual discriminatory power and high accuracy (94%).
  • Mass spectrometry-based multiple reaction monitoring assays combined with ELISA assays were set-up to monitor the 30 ß-cell biomarker panel.

For more information

Eustache Paramithiotis

Caprion Protéomique Inc.

Co-Investigators

Marc Prentki and Rémi Rabasa-Lhoret Université de Montréal

Mentors

Daniel Kemp Diabetes Program Team Lead, Merck & Co., New York, NY, USA

Sotorios Karathanasis Vice President Bioscience, AstraZeneca, Mölndal, Sweden