Scientific highlights

18.01.2018

miRNAs as target molecules to combat metabolic diseases

Over the next two years, Germany’s Federal Ministry of Education and Research (BMBF) will provide one million euros in funding for the ComboMiR project. The aim of the research is to target microRNAs to develop new therapeutic approaches to metabolic diseases. The project will be coordinated at the Helmholtz Zentrum München, where about 500,000 euros of the funding will remain.

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Diabetes is one of the most common diseases in Germany – an estimated one in ten people have the disease. Although blood glucose levels can be controlled by medication, many patients suffer from neural and vascular damage in the later stages of the disease. Up to now this has been virtually unpreventable and no satisfactory treatment has been available. “Affected patients are often subjected to complex drug regimens to control both their blood sugar and blood lipid levels and to treat the symptoms of late complications”, says Professor Stephan Herzig, Director of the Institute for Diabetes and Cancer, Helmholtz Zentrum München, who is coordinating the project. 

The scientists have now identified a group of so-called microRNAs (miRs) which play a key role in metabolic regulation. MicroRNAs are a class of molecules consisting of short sequences of RNA building blocks. Unlike in protein synthesis, however, RNA is not required in order to build molecules. On the contrary, many miRs are able to inhibit the formation of certain proteins by destroying the corresponding RNA blueprint. 

In previous experiments, individual miRs were eliminated by so-called Tough Decoys (TDs)*, resulting in a reduction in blood sugar and blood lipid levels. The TDs can be specifically designed to target several miRs simultaneously with one TD molecule. To this end, the researchers will pack the TDs in biologically degradable transport vehicles, thus enabling miRs to target specific organs. 

The University Hospitals in Leipzig and Heidelberg will also be involved in the project. The idea is that through the close proximity to applied medicine, clinical relevance based on a well-characterized patient collective will be demonstrated directly during the project. 

“In this way, several metabolic values could in future be controlled with one single biological preparation that is individually tailored to patients,” Professor Herzig says, explaining the objective of the project. “That would make it possible to substantially improve both the treatment and prevention of diabetes and its long-term complications.” 

Further Information

* Tough Decoys (TDs) are novel RNA oligonucleotides that can neutralize microRNAs with the aid of specific binding sequences. Their special spatial configuration makes it possible to combine antisense sequences for numerous miRs in one TD molecule and thus to bind several of these regulatory RNAs.  Since TDs are insensitive to nuclease degradation, they can be used to permanently inhibit specific miRs. Reference: Haraguchi et al 2009  
 

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. 

The Institute for Diabetes and Cancer (IDC) is a member of the Helmholtz Diabetes Center (HDC) at the Helmholtz Zentrum München and a partner in the joint Heidelberg-IDC Translational Diabetes Program. The Institute for Diabetes and Cancer is tightly integrated into the German Center for Diabetes Research (DZD) and into the special research area "Reactive Metabolites and Diabetic Complications" at the Heidelberg University Medical School. The IDC conducts research on the molecular basis of severe metabolic disorders, including metabolic syndrome and type 2 diabetes, as well as their roles in tumor initiation and progression.