Don't hold your breath: new Russian drug will defeat resistant tuberculosis in two weeks

Russian scientists have completed preclinical studies of a tuberculosis drug based on a bacteriophage, a virus that destroys Koch's bacillus without harming the human body. The drug has shown higher efficacy than classical antibiotics. In laboratory and animal experiments, the development has eliminated 50 different strains of tuberculosis, regardless of their drug resistance. At the same time, the duration of the fight against infection was reduced from six months to two weeks. According to doctors, the drug could potentially revolutionize the fight against Mycobacteria. However, first you need to confirm the results in trials on real patients.

Testing of bacteriophage D29

Specialists from the National Medical Research Center for Phthisiopulmonology and Infectious Diseases of the Russian Ministry of Health have completed preclinical studies of a new inhaled drug based on the natural mycobacteriophage D29, a special virus capable of destroying Mycobacterium tuberculosis. During the experiments, it showed its effectiveness against 50 different strains of Koch's bacillus, half of which were resistant to antibiotics. At the same time, the course of medication is only two weeks. The developers have received comprehensive data on the pharmacokinetics and the absence of toxic effects of the drug. Preparations are underway for the start of phase I clinical trials involving humans.

— It is a full-fledged drug against tuberculosis with a different mechanism of action than that of antibiotics. In preclinical studies, it has shown high efficacy without combination with classical medications. We sprayed D29 into animals and compared it with a standard combination of isoniazid and rifampicin, and our drug showed the best results. The standard courses of antibiotics are six and 12 months. We plan to use the drug within two weeks," said Vadim Avdeev, a researcher at the Russian Ministry of Health's Scientific Research Center for Medical Research.

During the first phase of clinical trials, doctors will evaluate the safety of the drug in healthy volunteers. The second phase will be devoted to testing the effectiveness on patients. The medicine will be tested both separately and in combination with other drugs.

— D29 can be used against any strains of tuberculosis. During the clinical trials, we used 25 drug-sensitive and 25 resistant variants. The bacteriophage destroyed them all. Two days will be enough for us to test its effectiveness against the resistant EurA1.1 strain. But I think it will work. Bacteria do not develop resistance to the bacteriophage. It affects them quickly enough, and the Koch bacillus genome simply does not have time to change," said Vadim Avdeev.

An easy task: scientists have assessed the risk of spreading a mutant strain of tuberculosis

What genetic changes help EurA1.1 evade the effects of antibiotics and what is the threat

Application for the Nobel Prize

Bacteriophages as a means of fighting infection have been known for a long time. This trend was actively developing in the Soviet Union. But with the development of antibiotics, the technique has faded into the background. Due to the increasing resistance of mycobacteria and the high toxicity of antibiotics, doctors are returning to this area again.

— Unlike antibiotics, the bacteriophage does not have a negative effect on the body. If a person has mycobacteria, he interacts with them, if not, he is simply eliminated. D29 is the first bacteriophage against mycobacteria in the form of a medicinal product in Russia, and it has no analogues in the world. Due to its liposomal shape, when it is "packaged" into microscopic fat spheres, the drug has a targeted effect on the infection," said the developer.

Photo: IZVESTIA/Polina Violet

Until recently, bacteriophages were considered one of the areas of combating drug-resistant tuberculosis. Almost complete safety for humans allows them to be included in any treatment regimen. However, the effectiveness of such treatment is severely limited, said Andrey Prodeus, chief pediatric allergist and immunologist at the Ministry of Health of the Moscow Region.

— In order to understand which strains a medicine can be used against, it is necessary to study the structure of the bacteriophage and conduct tests. If the drug can really destroy any strain of mycobacterial infection, even without a combination with antibiotics, this is a breakthrough for the Nobel Prize. After all, she is currently being treated for six months or a year with two or three drugs at once," said the doctor.

Find a treasure trove: a drug-resistant mutant strain of tuberculosis has entered the Russian Federation

Antibiotics are not always effective against this pathogen, while trials of a modern vaccine have been completed in Russia.

The results obtained at the preclinical stage need to be confirmed in real patients. It is also important to show that Koch's bacillus does not develop resistance to this bacteriophage, as the bacterium has learned to adapt to other viruses hostile to itself, said immunologist Mikhail Bolkov.

— If the effectiveness is confirmed in the clinic, the drug will not be able to completely replace antibiotics. Bacteria have developed resistance to other bacteriophages, so they need to be changed, just like classic drugs. Even if it doesn't apply to this virus, evolution always has some kind of adaptation mechanism," the expert said.

Photo: IZVESTIA/Polina Violet

According to him, the absence of side effects is a great advantage of bacteriophages, so they can be used to treat patients with concomitant diseases and weakened immune systems who suffer from tuberculosis most often.