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Friday, 7 November 2014

Could a common blood pressure drug completely reverse diabetes?

Diabetes is the seventh leading cause of death in the US, raising risks for heart attack, blindness, kidney disease and limb amputation. But researchers who have shown that a common blood pressure drug totally reverses diabetes in mice are about to begin a new clinical trial to see if it can do the same for humans.

Pancreas showing diabetes

The beta cells that produce insulin are attacked by the body's immune system in type 1 diabetes.

If the trial is successful, it could herald the first "cure" for an incurable disease that affects 12.3% of Americans over the age of 20 and costs the nation $245 billion each year.

The key to the groundbreaking approach that has been proven effective in mice are beta cells, which the researchers explain are "critical" in type 1 and type 2 diabetes. These cells are progressively lost in the wake of the disease due to programmed cell death, though the precise triggers for the deaths were previously unknown.

The researchers, from the University of Alabama at Birmingham (UAB) and led by Dr. Anath Shalev, have been working on this research for over a decade in UAB's Comprehensive Diabetes Center.

They explain that their previous research has shown that high blood sugar causes an overproduction of a protein called TXNIP - which is increased within beta cells in response to diabetes. Too much TXNIP in pancreatic beta cells leads to their deaths, stopping the body's efforts to produce insulin and further promoting diabetes.

However, in animal models, the team has found that verapamil - used to treat high blood pressure, irregular heartbeat and migraine headaches - lowers TXNIP levels in beta cells.

In fact, in mice with established diabetes and blood sugars over 300 mg/dL, verapamil "eradicated" the disease.

The video below describes how verapamil works in the wake of diabetes: 

Trial will not include immunosuppressive medications

Now, the UAB researchers have received a 3-year, $2.1 million grant from JDRF - the largest charitable supporter of type 1 diabetes research - to conduct a clinical trial in 2015 in humans.

Commenting on the upcoming trial, Dr. Shalev says:

"That is a proof-of-concept that, by lowering TXNIP, even in the context of the worst diabetes, we have beneficial effects. And all of this addresses the main underlying cause of the disease - beta cell loss.

Our current approach attempts to target this loss by promoting the patient's own beta cell mass and insulin production. There is currently no treatment available that targets diabetes in this way."

The trial, which will begin recruitment processes early next year, will include 52 people aged 19-45 within 3 months of receiving a type 1 diabetes diagnosis. They will then be randomized to receive either verapamil or a placebo for 1 year while continuing insulin pump therapy.

The participants will also be equipped with a continuous glucose monitoring system so they can measure their blood sugar continuously throughout the day.

A unique feature of this trial is that it will not include the use of any immunosuppressive or immune modulatory medications, which carry severe side effects and are used in most type 1 diabetes trials.

"This trial is based on a well-known blood pressure medication that has been used for more than 30 years and is unlikely to have any severe side effects," adds Dr. Shalev, who also notes that their study is backed by a wealth of data in different mouse models and human islets.

More information here.


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