Vall d'Hebron Research Institute leads European project for early treatment of blindness due to diabetes

BY BIOCAT

The Diabetes and Metabolism group at the Vall d’Hebron Research Institute (VHIR), headed by Dr. Rafael Simó, will coordinate a European consortium to investigate early treatment of diabetic retinopathy, the most common pathology suffered by diabetics (it affects roughly 80% of all patients that have been suffering from diabetes for more than 15 years). The project, called Eurocondor, will develop a controlled phase II and III clinical trial that will set out to test the effectiveness of somatostatin (a neuroprotective drug) in the early stages of the disease in order to prevent or delay its progression.

The European consortium is composed of 18 partners from eight countries and will begin work at the end of 2011. The VHIR research group has been chosen to lead the project as it was the first to publish the keys of neurodegeneration in the eyes of diabetic patients and to demonstrate the existence of a somatostatin deficit in these patients.

This multicentric research project, with a total cost of €6 millions, will have a direct impact on patients, as it is a significant step forward in preventing the disease and will open up a new benchmarking process. According to researchers, it will also be an important step forward in reducing economic costs derived from resulting medical visits and work leave. Finally, the findings could drive innovation leading to new developments in the pharmaceutical industry.

The unsuspected effects of fenofibrate

As part of the same line of research, the VHIR has discovered the molecular bases that make fenofibrate effective in treating diabetic macular edema (DME). Although the efficacy of this drug in preventing diabetic retinopathy and in slowing its progress in the early stages has already been proven, no one had explained why. This discovery allows specialists to recommend this drug, which is the only one that has been proven effective in treating this pathology when taken orally, with more confidence.

Macular edema, one of the alterations included in diabetic retinopathy, is the main cause of lack of visual acuity in patients with type 2 diabetes.

The group led by Dr. Rafael Simó based their research on the fact that DME is produced by an inflammatory process with elevated glucose levels. Their findings, recently published in the journal Diabetología, show that the main cause of this disorder is inflammation developed because proteins (interleukin 1B) activate an energy sensor in the cells (AMPK). This activation causes retina cells to lose their ability to act as a barrier, allowing the passage of fluids. This leads to a build-up of fluids and, thus, macular edema. Scientists at Vall d'Hebron have shown that fenofibrate is able to block AMPK and, therefore, to control inflammation and stop the edema.

Fenofibrate has been used for many years as a lipopenic drug, which reduces blood fat levels. A study that sought to establish the relationship between the reduction of these fat levels through use of fenofibrate in diabetics and the progression of diabetic retinopathy discovered that fenofibrate is effective in stopping the progress of this disease. “In fact”, explains Dr. Simó, “it reduces the need for laser photocoagulation treatment, commonly used in the more advanced stages of the disease, by 30%.” Curiously, however, the effects have no connection to the reduced fat levels. This fact has led current studies to look into the mechanisms through which fenofibrate works.

Fenofibric acid prevents retinal pigment epithelium disruption induced by interleukin-1? by suppressing AMP-activated protein kinase (AMPK) activation. Authors: M. Villarroel, M. Garcia-Ramírez, L. Corraliza, C. Hernández and R. Simó (Diabetologia 2011; 54:1543-53).

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