News & Research

    Washington University in St. Louis, St. Louis, Missouri

Identifying biomarkers for an endoplasmic reticulum (ER) stress related diabetes

General Research Subject: Type 2 Diabetes

Focus: Clinical Therapeutics/New Technology\Pharmacologic Treatment of Diabetes or its Complications

Type of Grant: Clinical Translational Research

Project Start Date: January 1, 2012

Project End Date: December 31, 2014

Diabetes Type: Type 2 diabetes

Research Description

Identifying disease mechanisms in type 2 diabetes (T2D) is complicated by contributions of multiple genes and environmental factors. The current study proposes a novel strategy that will assess patients with Wolfram syndrome (WS), a disease caused by a single mechanism that causes stress in the cells endoplasmic reticulum (ER). WS is a rare, progressively fatal form of diabetes for which there is no treatment. A major barrier to developing new therapies has been lack of careful documentation of the natural history. Aim 1 will clinically assess patients who will undergo endocrine, neuroimaging, neuropsychological, motor, psychiatric, visual and auditory evaluations.

The hypothesis is that these measures will lead to the discovery of potential biomarkers to monitor disease progression.

A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Aim 2 will determine structural and functional biomarkers that change reliably with time and disease progression. Change in variables identified in Aim 1 will be re-assessed annually and correlated with change in disease severity.

The hypothesis is that selected measures will show detectable yearly change, and that these changes will serve as biomarkers for embarking on clinical trials with agents designed to moderate ER stress. In this clinical study, documenting the natural history of WS will facilitate embarking on clinical trials of agents that will ultimately be useful for the treatment of ER stress that is a sIdentifying disease mechanisms in type 2 diabetes (T2D) is complicated by contributions of multiple genes and environmental factors.

The current study proposes a novel strategy that will assess patients with Wolfram syndrome (WS), a disease caused by a single mechanism that causes stress in the cells endoplasmic reticulum (ER). WS is a rare, progressively fatal form of diabetes for which there is no treatment. A major barrier to developing new therapies has been lack of careful documentation of the natural history.

Aim 1 will clinically assess patients who will undergo endocrine, neuroimaging, neuropsychological, motor, psychiatric, visual and auditory evaluations. The hypothesis is that these measures will lead to the discovery of potential biomarkers to monitor disease progression. A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.

Aim 2 will determine structural and functional biomarkers that change reliably with time and disease progression. Change in variables identified in Aim 1 will be re-assessed annually and correlated with change in disease severity.

The hypothesis is that selected measures will show detectable yearly change, and that these changes will serve as biomarkers for embarking on clinical trials with agents designed to moderate ER stress. In this clinical study, documenting the natural history of WS will facilitate embarking on clinical trials of agents that will ultimately be useful for the treatment of ER stress that is a significant part of T2D and other diseases significant part of T2D and other diseases.

Research Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

Determining the etiology of ER stress mediated diabetes.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

Knowledge of the etiology of diabetes with possible new therapeutic agents to treat.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?

I have been involved in diabetes research for 40 years.

In what direction do you see the future of diabetes research going?

Forward to a cure.