Hope in the battle against common diseases

2018/03/22

Hope in the battle against common diseases

Biochemists of TU Darmstadt develop substances fighting obesity

A team led by biochemistry professor Felix Hausch of the TU Darmstadt is working on substances that are to help fighting three widespread diseases: depression, chronic pain and obesity.

Kleine Moleküle ganz groß: Prof. Hausch inspiziert ein Modell für neue Wirkstoffe gegen Schmerz, Fettleibigkeit und Depression. Bild: Katrin Binner
Small molecule, large effect: Prof. Hausch inspecting a model for new substances against pain, obesity and depression. Image: Katrin Binner

In Germany, around four million people suffer from depression. And according to a study by the Deutsche Schmerzgesellschaft, the German Pain Society, as many as eight to 16 million people are affected by chronic pain. Nor is the situation any better when it comes to our weight: around one in six of us here is obese. Biochemically, there is a link between these three common diseases. Our body produces a protein molecule called FKBP51 that plays an important role both in energy metabolism and in depression and chronic pain.

Felix Hausch, since October 2016 Professor for Structure-Based Drug Discovery at the TU Darmstadt, believes this protein is an interesting point of attack for future medicines. “If you block FKBP51, then the tendency towards depression, obesity and chronic pain should decrease.” As the starting point for the development of inhibitors, Professor Hausch's team opted for the already approved pharmaceutical substance Tacrolimus, a substance obtainable from bacteria that is known to bind to FKBP51, but also to similar proteins. The researchers changed this substance chemically so that it inhibits FKBP51 even more efficiently, but also only blocks this protein and not any of its relatives.

Two variants of the substance

Today, the scientists are working with two variants of the active substance. One moves past the blood/brain barrier and is considered a candidate in the battle against depression and chronic pain. The other does not pass to the brain, and could be used to fight obesity. Initial studies in mice were promising and had no side effects. Even mice in which FKBP51 production had been entirely switched off genetically did surprisingly well: they survived for a similar period of time, moved around the same and ate just as much as their non-manipulated littermates. Incidentally, the inhibition of FKBP51 only acted on chronic pain in animal trials, and did not affect the acute perception of pain. “This is very important,” emphasises Hausch, “as otherwise we would, for instance, burn our hands on a hot cooker.”

Current results are highly promising, but the development of the substance is by no means over. “We still need to improve a few molecular properties,” says Hausch. It will probably take some time until the substance is ready for the market, especially as development costs are growing exponentially. For instance, the clinical tests on thousands of volunteers – essential in the approval process for any new drug – are extremely expensive. As a university is not the right setting for these studies, the biochemistry professor is already considering starting a company.

Current publications

Georgia Balsevich et al.: Stress-responsive FKBP51 regulates AKT2-AS160 signaling and metabolic function, Nature Communications, 2017, 8(1):1725, DOI: 10.1038/s41467-017-01783-y

“The Stress Regulator Fkbp51: A Novel and Promising Druggable Target for the Treatment of Persistent Pain States Across Sexes.” PAIN, 2018. DOI: 10.1097/j.pain.0000000000001204

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