New preclinical drug candidate shows promise in eradicating gonorrhea bacteria

New preclinical drug candidate shows promise in eradicating gonorrhea bacteria

A new preclinical drug candidate developed by scientists at the Hackensack Meridian Center for Discovery and Innovation (CDI) shows promise in eradicating the bacteria that causes gonorrhea, according to a new publication.

JSF-2659, designed for oral administration, could be a game-changer in the treatment of Neisseria gonorrhoeae, which is on the World Health Organization's global list of "priority pathogens" due to its resistance to existing drugs.

This compound is promising and directly addresses an emerging health threat. We need more and better medicines. This molecular strategy could also be very promising for pathogens beyond this one type of bacteria.”

David Perlin, Ph.D., Chief Scientific Officer and Senior Vice President of CDI

The parent compound, JSF-2414, acts on two molecular targets simultaneously, making it particularly effective at inhibiting the bacteria's DNA replication, according to the article in the journal Antimicrobial Agents and Chemotherapy, a publication of the American Society for Microbiology.

The dual-targeting strategy means more bacteria are wiped out - and the lack of survivors and very low probability of modifying two cellular targets during therapy means a lower chance of increasing drug resistance, according to the different CDI models of the active drug against N. gonorrhoeae.

The tests included 96 different strains of the gonorrhea bacterium. But it also showed effectiveness against other gram-positive germs such as methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Enterococcus faecium, Clostridium difficile and other species.

The new drug candidate, if advanced to clinical development in humans, would add to a list of drugs that have lost effectiveness in recent decades. According to the paper, "There is now a high prevalence of N. gonorrhoeae strains that are resistant to common antimicrobial classes used for treatment, including sulfonamides, penicillins, cephalosporins, tetracyclines, macrolides and fluoroquinolones. such as cefixime and ceftriaxone, have resulted in a major health crisis." led.” In many developing countries, ceftriaxone is the monotherapy drug of last choice.

Accordingly, gonorrhea is a "major public health problem" that infected more than 82 million new people worldwide last year, according to the World Health Organization, bringing with it increasing resistance to such treatments. The WHO added multidrug-resistant gonorrhea to its list of “priority pathogens” in 2017.

Research on compound JSF-2659 was led by CDI's Center of Excellence in Translational Research (CETR), funded by a grant from the National Institutes of Health. Authors of the paper included Perlin and members of his CDI laboratory, as well as experienced microbiologist Barry Kreiswirth, Ph.D., and members of his laboratory, and also colleagues include Joel Freundlich, Ph.D. from Rutgers University.

“CDI's work continues to push the boundaries in many ways,” said Ihor Sawczuk, MD, FACS, president of academics, research and innovation at Hackensack Meridian Health and associate dean for clinical integration and professor emeritus and chair of urology at Hackensack Meridian School of Medicine. “The world is better for their scientific contributions.”

Source:

Hackensack Meridian Health

Reference:

Park, S., et al. (2022) A novel oral GyrB/ParE double bond inhibitor effective against multidrug-resistant Neisseria gonorrhoeae and other highly threatening pathogens. Antimicrobials and chemotherapy. doi.org/10.1128/aac.00414-22.

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