Diabetic Complications
Research investigating the use of Triethylenetetramine (TETA) for complications of diabetes
Outline
Diabetes affects approximately 280 million people worldwide and this number is expected to double over the next 20 years. It is a condition where there is too much sugar in the blood due to the pancreas, which controls the amount of blood sugar by secreting insulin, not working properly. In the long term the high sugar levels cause progressive damage to many parts of the body including the heart, blood vessels, kidneys, eyes and nerves.
Our researchers are developing drugs that prevent the damage to the pancreas that initiates the commoner form of diabetes, called type 2 diabetes. We are also working on ways to replace the damaged cells in the pancreas. In addition, we are testing a drug called triethylenetetramine (TETA) which does not alter the blood sugar levels, but we think can treat the long-term damaging consequences of diabetes.
Problem
The longer a patient suffers from diabetes the more likely they are to develop problems with the heart and circulation, eyesight, nerves and kidneys. These problems are partly due to the accumulation of copper(II) in these tissues. The excess of copper(II) initiates a series of damaging chemical reactions that ultimately destroy cells in the body.What we have achieved to date
Our work to date has shown that in diabetes the accumulation of extracellular copper(II) drives the production of hydroxyl radicals, and this in turn results in tissue damage. Our researchers have shown that it is possible, using triethylenetetramine (TETA), to remove the excess of copper(II) from the body in diabetes patients, which can prevent and even reverse the tissue damage.
TETA is a highly selective chelator of copper (II) that can remove copper(II) from tissues, which is then secreted in the urine, without leading to copper deficiency (as most of the copper in the body is copper(I)). Preclinical experiments have shown that oral TETA treatment can prevent and even reverse diabetic heart failure, nephropathy and retinopathy. Furthermore, Phase 1 and Phase 2 trials for diabetic heart failure have shown positive results with TETA treatment.
What we aim to achieve
Our aim is to undertake clinical trials to see whether TETA has beneficial effects in preventing or reversing the complications of diabetes in a number of tissues. Phase 1 and Phase 2 trials for diabetic heart failure have shown positive results with TETA treatment. We now plan to build on these studies on the heart and test the effects of TETA in further Phase 2 trials, investigating its effects on vascular stiffness, diabetic nephropathy, retinopathy and neuropathy. We then aim to progress the TETA treatment to a definitive Phase 3 trial.
A promising sign for this study is that TETA is already used as a treatment for a rare genetic disease, called Wilson’s disease. This means it will be much easier to develop into a treatment for diabetes rather than a new drug with no previous patient use.
