Rewriting Life

DNA-Based Research May Have Unveiled Long-Sought Diabetes Treatment

A synthetic drug that controls blood sugar in obese mice demonstrates the potential of a DNA-dependent method for developing new chemical compounds.

The World Health Organization predicts that diabetes will be the seventh-leading cause of death by 2030.

After decades of searching, researchers may have finally identified a chemical compound that could be used to study and treat diabetes.

Researchers have long known that the body carries an enzyme that breaks down insulin inside cells and helps regulate the body’s response to sugars—a process that goes awry in type 2 diabetes. Genetic studies have shown that people with type 2 diabetes are more likely to have mutations in the gene that encodes a protein called insulin-degrading enzyme, or IDE. But exactly which processes the enzyme controls is not yet clear.

David Liu and his team at Harvard have identified a chemical compound that can inhibit IDE, and they have shown that the compound increases the amount of insulin in the bloodstreams of both normal mice and ones made obese by an unhealthy diet.

Liu and his team developed the new compound using a novel method called DNA-templated synthesis. This involves linking thousands of different chemical structures to thousands of unique DNA strands, and then taking advantage of the interactions between two strands of DNA to bring the chemical building blocks together to create new ones.

Patients with type 2 diabetes either have an insufficient amount of insulin in their blood or do not properly respond to the hormone in order to move the body’s main energy source—glucose—into cells. Researchers have speculated for decades that a drug that could inhibit IDE might help some type 2 diabetes patients.

Small-molecule drugs, which make up the majority of medicines, are compounds far smaller than less common biological medicines like antibodies. They are developed using libraries of thousands or millions of known chemical substances. Each compound is screened to see if it has a desired effect on a biological target, such as an enzyme or other protein known to be involved in a disease. Pharmaceutical companies may use robotics to test many chemical reactions in parallel.

DNA-templated synthesis allows researchers without a lot of expensive equipment to more quickly evaluate all the potential small molecule interactions that could occur from a library of building blocks. “A single student with only minimal equipment and infrastructure can evaluate millions of potential small molecule-protein interactions in one to two weeks,” says Liu.

Furthermore, DNA-templated synthesis can produce structures that are often not found in chemical libraries used by many pharmaceutical companies, which may be why the Harvard team was able to identify an IDE-controlling drug when so many had failed in the past.

The newly identified IDE inhibitor could be the starting point for developing a powerful new drug for type 2 diabetes. Another compound was previously known to inhibit IDE, but it had unwanted side effects, and it survived for only a few minutes in the body. The new inhibitor lasts for hours, says Liu.

Tech Obsessive?
Become an Insider to get the story behind the story — and before anyone else.

Subscribe today

Uh oh–you've read all of your free articles for this month.

Insider Premium
$179.95/yr US PRICE

More from Rewriting Life

Reprogramming our bodies to make us healthier.

Want more award-winning journalism? Subscribe and become an Insider.
  • Insider Premium {! insider.prices.premium !}*

    {! insider.display.menuOptionsLabel !}

    Our award winning magazine, unlimited access to our story archive, special discounts to MIT Technology Review Events, and exclusive content.

    See details+

    What's Included

    Bimonthly home delivery and unlimited 24/7 access to MIT Technology Review’s website.

    The Download. Our daily newsletter of what's important in technology and innovation.

    Access to the Magazine archive. Over 24,000 articles going back to 1899 at your fingertips.

    Special Discounts to select partner offerings

    Discount to MIT Technology Review events

    Ad-free web experience

    First Look. Exclusive early access to stories.

    Insider Conversations. Listen in as our editors talk to innovators from around the world.

  • Insider Plus {! insider.prices.plus !}* Best Value

    {! insider.display.menuOptionsLabel !}

    Everything included in Insider Basic, plus ad-free web experience, select discounts to partner offerings and MIT Technology Review events

    See details+

    What's Included

    Bimonthly home delivery and unlimited 24/7 access to MIT Technology Review’s website.

    The Download. Our daily newsletter of what's important in technology and innovation.

    Access to the Magazine archive. Over 24,000 articles going back to 1899 at your fingertips.

    Special Discounts to select partner offerings

    Discount to MIT Technology Review events

    Ad-free web experience

  • Insider Basic {! insider.prices.basic !}*

    {! insider.display.menuOptionsLabel !}

    Six issues of our award winning magazine and daily delivery of The Download, our newsletter of what’s important in technology and innovation.

    See details+

    What's Included

    Bimonthly home delivery and unlimited 24/7 access to MIT Technology Review’s website.

    The Download. Our daily newsletter of what's important in technology and innovation.

/
You've read all of your free articles this month. This is your last free article this month. You've read of free articles this month. or  for unlimited online access.