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New drug discovered against chronic infections
Chronic infections are often difficult to treat and associated with significant health problems for those affected. A new drug could significantly improve the treatment options in the future, according to a recent study by the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) and the German Center for Infection Research (DZIF)..
"Chronic lung infections caused by the bacterium Pseudomonas aeruginosa," according to the researchers, "require a complex and mostly permanent antibiotic therapy." The complete cure, or at least an increased suppression of bacterial load is thus usually not possible. Hope, however, offers an optimized anti-infective agent with a new mechanism of action, which the scientists have tested in their current study.
Chronic lung infections are currently difficult to treat, but scientists have now discovered a new drug candidate for their therapy. (Image: artstudio_pro / fotolia.com) Block pathogenicity of bacteria
New medicines for chronic lung infections are urgently needed and the researchers say they have now achieved a major breakthrough. They have successfully adapted an anti-infective agent with a new mechanism of action for the treatment of chronic lung infections. The starting point was a substance that can block the pathogenicity of the bacterium and weaken its biofilm protection shield, the scientists report. Overall, the Helmholtz Validation Fund, the DZIF and the Helmholtz Center for Infection Research jointly invested 2.7 million euros in the optimization of this substance class - "with the goal of a preclinical development candidate."
Bacteria are not killed
Dr. Martin Empting, who is working on the project at HIPS / HZI together with Prof. Rolf Hartmann and Dr. med. Thomas Hesterkamp stresses that the researchers put great hope in these drug candidates. The so-called pathoblocker acts differently from an antibiotic and does not kill the bacterium, but interferes with its ability to damage the host and protect itself from the immune system by biofilm formation. Thus, "the bacterium is also more susceptible to a parallel antibiotic therapy", Dr. Empting on.
Pseudomonas aeruginosa a dangerous hospital germ
According to the researchers, the active substance, which attacks the bacterial receptor PqsR (also called "MvfR"), shows a selective and specific anti-Pseudomonas aeruginosa effect. Other bacteria that could be useful would be spared. According to the scientists, it is also feared as a hospital germ and is listed on the World Health Organization's (WHO) Priority Pathogens List as one of the three major pathogens for the development of new drugs. The bacterium attacks respiratory and urinary tracts or wounds and causes dangerous infections. Their treatment is extremely difficult today.
Risk patients for a chronic lung infection
According to the researchers, "Patients suffering from cystic fibrosis" are particularly often affected by corresponding chronic infections. In their case, the pathogen causes a chronic lung infection that must be kept permanently in check with antibiotics. In addition, patients with obstructive airway diseases or dilated bronchi (so-called bronchiectasis) are increasingly affected by infections with the pathogen. Increasing antibiotic resistance also makes successful treatment difficult for them.
Suppresses virulence process and reduces biofilm formation
The scientists were able to prove in their investigations that the starting molecule offers good conditions for the development of a successful drug. The pathoblocker inhibits the function of the receptor PqsR, which plays a key role in the infection process of Pseudomonas aeruginosa. "Through this receptor, the bacterium regulates its group-specific virulence and thus factors that are responsible for the severity of the infection," reports the DZIF. On the one hand, the new active substance suppresses the virulence process and on the other hand it demonstrably reduces "the mass of biofilm, a matrix that is formed by pseudomonads and protects the bacteria from attacks by the immune system." With the formation of a biofilm, an infection in usually chronic and difficult to treat.
Further development to the practically applicable active substance planned
In the next step, according to the researchers, the drug designers are in demand to change the structure of the molecule so that it has the necessary properties for a drug. For example, high activity on the target structure, high selectivity and good availability at the site of action must be ensured. The aim of the research is to determine a preclinical profiling candidate in the next two years, which can then be further developed in collaboration or as part of a company spin-off.
"At the end of development, an active ingredient should be available that can be inhaled by patients with chronic lung infections," emphasizes Dr. med. Empting. A promising first area of application here is the use as an adjunct therapy for antibiotic treatment. The development of pathoblockers, according to Dr. In principle, however, Empting is "an important option for sustainably managing the problem of difficult-to-treat chronic infections." (Fp)