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We talk about the treatment of systemic mycoses and work on new drugs prof. Edward Borowski, specialist in the field of drug chemistry and the discoverer of the first in Poland antibiotic tetaine. The scientist is associated with the Gdańsk University of Technology and with a research and development company Blirt (Biolab Innovative Research Technologies), conducting activities in the field of medical biotechnology.
As part of this company, a team of scientists from the Gdańsk University of Technology under the supervision of professor Edward Borowski developed new drugs – innovative derivatives of antifungal antibiotics that can be widely used in the effective and less toxic treatment of systemic mycoses, one of the most dangerous civilization diseases of our time. It is a great success of Polish scientists and a great hope for the sick who struggle with mycosis.
– Professor, how are systemic mycoses treated in Poland?
– Chemotherapy of infection with fungal microorganisms is one of the most difficult and so far unsolved problems in modern medicine. In the treatment of systemic mycoses, drugs from four groups are used: polyene antibiotics (amphotericin B), azoles (e.g. fluconazole), antimetabolites (5-fluorocytosine) and echinocandins (e.g. caspofungin).
– Please describe the polyene antibiotics?
– It is a group of biologically active compounds with a specific structure, in the molecule of which there is a multi-membered ring closed with a lactone bond. The most popular representatives of this group used in the treatment of mycoses are amphotericin B and nystatin. Another antibiotic in this group is natamycyna, mainly used in the case of fungal infections within the eyeball.
— Do drugs used so far in the treatment of systemic mycoses are effective? What side effects do they cause?
— A very disturbing phenomenon is the steady decline in the effectiveness of antifungal drugs. This is due to the high toxicity of the currently used compounds, which makes it impossible to apply the appropriate doses without troublesome side effects. Another reason for the decline in the effectiveness of these drugs is the rapid development of resistance of fungal strains to these compounds. Especially clinically valuable azole drugs, such as miconazole, voriconazole or posaconazole, often cause the phenomenon of fungal cell resistance to their effects. This is due to a variety of mechanisms, the most dangerous of which is the removal of the drug from the fungal cells through transport pumps located in the fungal cell membrane. Despite the risk of resistance, azoles are widely used, incl. due to their availability and relatively low cost of therapy. Caspofungin is a valuable antifungal drug with which high hopes were raised. It causes fewer side effects, but can also lead to resistance to fungal cells. Another problem is its very high price. 5-Fluorocytosine, often used in combination with Amphotericin B, is also prone to the development of resistance. The most common side effect of both azoles and caspofungin antifungals is their adverse effect on the liver, and in some cases, kidney damage, nausea, and vomiting can also occur.
Thus, practically only one systemic drug remains on the battlefield, Amphotericin B from the group of polyene antibiotics. This is the so-called “gold standard” that has been used for over 40 years in the treatment of mycoses. This antibiotic does not lead to the development of resistant strains, nor is it removed from cells via transport pumps, which results in its full activity, also in relation to multi-drug resistant strains. On the other hand, the main problem in the case of Amphotericin B is its high toxicity, leading to damage mainly to the kidneys and liver. There are forms of this drug that are safer for patients: lipid and liposomal forms, but their very high cost precludes their widespread use.
– What is the innovation of the new compounds developed by the Professor’s team?
Optimal antifungal drugs should effectively eliminate the infection present in the body with minimal impact on the patient’s health. It is very difficult to achieve due to the similar structure and functioning of the cells of fungi and cells of the human body. Hence, significant difficulties arise in obtaining drugs that act selectively, and therefore have low toxicity for the patient. The innovation of Amphotericin B and nystatin derivatives developed by us – which may ultimately be a drug – is based on a significant reduction in their toxicity and a significant increase in solubility in water. The new derivatives are characterized by a broad spectrum of fungicidal activity, high activity, no resistance problem and, most importantly, reduced toxicity compared to the starting compounds.
– When are new drugs likely to enter clinical practice?
— The compounds developed by our research team are currently at the stage of preclinical laboratory research. In order to introduce new derivatives to the market of antifungal drugs, it is necessary to perform clinical trials that may last up to several years. The developed drugs will be able to be used not only in the treatment of severe systemic mycoses, but also in the treatment of superficial infections, and the low toxicity combined with the lack of the risk of resistance development will also allow their use in antifungal prophylaxis in patients particularly at risk of developing these infections.
It is worth emphasizing that the costs of prophylaxis and antifungal treatment in developed countries are higher each year. This is due both to the growing number of infections, which have taken epidemic proportions worldwide, and their increasing resistance to treatment. Currently, the value of the global antifungal drugs market is estimated at approximately USD 11 billion annually.
Text by Barbara Skrzypińska