Jena scientists discover TB drug | TLZ

Jena. Scientists from the Jena Hans Knöll Institute are currently waiting Neu-Ulm . In the Bavarian city, researchers from a study center are testing the substance BTZ043. Behind this is a new antibiotic, which will very effectively combat the TB virus in the future. Researchers from Jena discovered the substance that is being tested on humans for the first time.

"The active ingredient binds irreversibly to an enzyme that the mycobacteria – the agents responsible for tuberculosis – must reconstitute the bacterial wall ", explains Florian Kloß Head of the group of transfer of antiinfectives at the Leibniz Institute for the research on natural products and the biology of infections Jena better known as the Hans Knöll Institute. This enzyme can not work through the drug. In the cell walls of mycobacteria appear holes and they leak. "This attack against TB pathogens is so targeted that BTZ043 only fights pathogens, but not the other bacteria that are important to us," Kloß says.

The discovery is in the tradition of the institute. "Tuberculosis has always been one of the research topics," says Michael Ramm of the scientific organization of the Hans Knöll Institute. The Jenaer institution produced the BCG vaccine (Bacillus Calmette-Guerin) for all Eastern Europe in the GDR. Even today, the Cross of Lorraine is installed on a campus for the fight against tuberculosis.

In parallel, the institute conducted research to find new drugs against the infectious agent. The microbiologist Ute Möllmann worked on a promising substance in the early 1990s. She met Russian chemist Vadim Makarov who wanted to use the labs during the summer holidays to Jena . This has resulted in years of cooperation. Finally, it was possible to synthesize the highly active molecule against tuberculosis. The Jenaer has filed the patent for the substance.

Resistance to antibiotics as a driver

But the road to a drug is far away. Since 2014, researchers have collaborated with the Ludwig Maximilian University Hospital in Munich (LMU), among others, the InfectControl 2020 consortium and the German Infection Research Center to further develop the drug. Thuringia has developed badytical methods of detection. They studied in animal experiments how the substance is absorbed, circulated in the bloodstream and taken into account in the metabolism.

The researchers suggest that the problem of antibiotic resistance in the world has dramatically worsened in recent decades. "Today we are faced with the challenge that there are more and more resistant germs, against which only a few antibiotics help," says Kloß . In the case of tuberculosis, the situation is particularly difficult, because several antibiotics must always be given at the same time for their treatment. In addition, TB pathogens are increasingly resistant to these antibiotics. "To develop new forms of therapy, several new active substances are urgently needed, ideally with different mechanisms of action" Kloß .

Axel Brakhage director of the Jena Institute and professor at the Friedrich Schiller University, follows the development of the drug since its discovery: "This requires immense effort financial and organizational when publicly funded institutions in the development of drugs, "says Professor. "The threat of multidrug-resistant pathogens, however, makes it absolutely necessary to counter the industry on this less lucrative path."

As a sponsor, the LMU clinic is responsible for preclinical and clinical development as well as the quality and safety of the drug. The highly effective substance is produced by Hapila in Gera . In addition, the company develops the manufacturing process in accordance with all relevant provisions of the pharmaceutical legislation as well as international regulations.

Now they are testing the substance on humans for the first time. 40 volunteers, healthy participants receive the antibiotic at the study center at Neu-Ulm . "We want to make sure that the drug is well absorbed and tolerated in the body.To this end, a very small dose is administered once, which is then increased step by step in the next subject," says Michael Hoelscher Director of the Tropical Institute of Ludwig-Maximilians-Universität Munich .The purpose of the study is to reach the dose that has shown good efficacy in the animal model

If this phase 1 study is successful, the tests will start on how a subject tolerates multiple doses.Only in the second phase, the drug is used on sick patients – at best, it will succeed in 2020. "This is done in combination with another preparation," explains Dumpling Again, given the successful deployment, there are two independent approval studies. must re 2000 and 8000 patients in several hospitals, if possible on different continents. Dumpling : "These tests must certify that the drug is at least as good as other drugs on the market."

This procedure not only takes a lot of time but also costs a lot of money. 500 million euros, these are conservative estimates, it takes for the approved drug. But only one in ten drugs, entering a phase 1 study, eventually reaches market maturity. Tuberculosis is a rare disease in the Western world, and the consortium could benefit from accelerated approval procedures. "We have already received the first positive decisions," says Kloß . But first, the drug must cross the first hurdle to the test of Neu-Ulm .

Tuberculosis

• This is an infectious bacterial disease worldwide
• According to the World Health Organization (WHO), nearly nine million people suffer from tuberculosis each year and about 1.4 million people die each year This disease, often due to inadequate treatment.
• According to the Robert Koch Institute, the infection is usually caused by people who have open pulmonary tuberculosis. By coughing or sneezing, bacteria spread in the environment.
• The incubation period is between six and eight weeks
• The treatment of tuberculosis is a combination of drugs.
• The rapid detection of the disease, the isolation of infectious patients and a fast and effective therapy are decisive for effective control. .