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Saghatelian, Alan , PhD

    Harvard University, Cambridge, Massachusetts

Proteolysis-resistant peptide hormone analogs as potential anti-diabetic therapeutics

General Research Subject: Type 2 Diabetes

Focus: Clinical Therapeutics/New Technology, Clinical Therapeutics/New Technology\Pharmacologic Treatment of Diabetes or its Complications, Integrated Physiology, Integrated Physiology\GLP-1, GIP, and Other Gut Hormones, Islet Biology, Islet Biology\Hormone Secretion and Exocytosis

Type of Grant: Innovation

Project Start Date: July 1, 2012

Project End Date: June 30, 2014

Research Description

Most drugs that are currently on the market are based on small molecules, which are low molecular weight chemicals typically consisting of a small number of carbon, hydrogen, oxygen and nitrogen atoms. While small-molecules make effective medicines there is a great deal of research that has to be carried out before a compound with the desired functional properties can be found. Alternatively, the human body produces a number of peptide hormones that are already known control important physiological processes. It would seem intuitive then to just use natural hormones as medicines to effect desired physiological responses. To treat type 1 diabetes, for example, which is caused by a loss of insulin, patients simply take insulin. Unfortunately, insulin is the exception and not the rule, and most other peptide hormones cannot be used as drugs because they are degraded too quickly (seconds to minutes) in the body to be effective drugs. In this application, we propose to use an innovative approach that relies on cutting-edge technology to engineer stable, biologically active, versions of natural peptide hormones that can be used as drugs to treat type 2 diabetes.

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?

Our research looks to see if we can develop biologic drugs for the treatment of diabetes by mimicking peptide hormones. There is currently one such drug on the market and it is based on a peptide hormone called GLP-1. By developing compounds based on other peptide hormones, specifically PACAP and PHI-27, we will test whether there are other compounds that may be of therapeutic benefit. We hope that these studies will eventually lead to the development of new therapeutics for the treatment of diabetes.

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

Our research project seeks to identify new peptide-based drugs for the treatment of diabetes. If successful, we will have compounds that can be used on their own or in combination with known drugs that can improve or reverse the symptoms associated with diabetes.

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

Diabetes is a terrible affliction that can negatively impact people’s lives for many years. My goal is to develop novel therapeutics for the treatment of diabetes by taking natural compounds that have beneficial properties (i.e. peptide hormones) and modifying them to be more drug like. This award is absolutely a necessity for being able to get this project off the ground.

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

I think that the recent emergence of biologics (antibodies and peptides) as successful drugs in a variety of fields will open the floodgates for novel therapeutic approaches. One of these approaches, and the one we take here, will be to manipulate the bodies hormonal signaling for therapeutic gain. Since we are starting with compounds that are already active and safe in humans the hope is that we can build better therapeutics.

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