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Leishmaniasis, a neglected tropical disease prevalent across 90 countries, affects approximately 12 million people worldwide, with 350 million more at risk of infection. Caused by unicellular parasites known as Leishmania protozoa, the disease commonly manifests as skin sores that can develop into deep ulcers.

Beyond the physical damage to the skin, leishmaniasis can leave permanent scars on patients' faces, hands, and feet, often leading to social stigma and psychological trauma. Unfortunately, the disease predominantly strikes poor communities, where medical care is often out of reach.

While various treatments for leishmaniasis do exist, they face severe limitations. Current drugs, such as antimonial compounds and amphotericin B, are hindered by high toxicity, serious side effects, and prohibitively high costs, leaving many patients unable to complete therapy.

Adding to these challenges, drug resistance is becoming increasingly common. Combined with the absence of vaccines and efficient diagnostic tools, these issues leave health care providers with inadequate weapons against a disease that continues to spread.

Against this backdrop, a research team led by Associate Professor Kanami Mori-Yasumoto from the Faculty of Pharmaceutical Sciences at Tokyo University of Science, Japan, has made a discovery that could transform leishmaniasis treatment. The team isolated 10 natural compounds from the marine sponges collected in Manza, Okinawa. Their findings were published in the journal on September 5, 2025.

The researchers analyzed extracts from Theonella sponges, focusing on a group of compounds called onnamides. Through careful laboratory testing, they discovered that several of these compounds showed remarkable effectiveness against Leishmania major, a representative species of parasite that often causes skin leishmaniasis. Among them, onnamide A and 6,7-dihydro-onnamide A were the most impressive, both demonstrating potency and a favorable safety profile far exceeding current treatments.

Further investigation into the mechanism of action of these compounds revealed another exciting finding: onnamide A appears to combat L. major through a pathway distinct from that of amphotericin B, which typically works by interacting with ergosterol in the parasite's cell membrane. This could guide scientists to new approaches to treatment, helping them overcome existing drug resistance. Moreover, the discovery of onnamide G, whose structure was revealed for the first time in this study, also provides new insights into the structural diversity and potential mechanisms of action of onnamides.

Notably, these onnamides not only effectively killed the parasite, but also spared human cells, thanks to their low toxicity and high selectivity. These advantages position onnamides as highly promising compounds for the development of new treatments for leishmaniasis.

"It may also be possible to apply these compounds to other protozoan diseases, such as Chagas disease and African sleeping sickness," adds Dr. Mori-Yasumoto, highlighting the broader impact of this study.

Furthermore, onnamides may exhibit pronounced activity at low concentrations, compared to existing treatments. This adds the advantages of reducing treatment duration and dosage. However, extended analyses are required to provide definitive conclusions regarding cost-effectiveness, in vivo efficacy, and in vitro pharmacokinetics before the initiation of clinical development.

Further research is being conducted to verify the potential of onnamides as suitable lead compounds in the AMED Drug Discovery Booster program, a Japanese initiative focused on supporting scientific studies to turn promising drug candidates into new medicines.

In terms of scalability, Dr. Mori-Yasumoto notes, "It may be possible to develop mass-production platforms for onnamide synthesis using modern culturing technology and symbiotic bacteria, ensuring a sustainable source." Using symbiotic bacteria as a viable strategy can lead to scalable and environmentally responsible drug production.

Furthermore, co-authors Dr. Junichi Tanaka and Dr. Takahiro Jomori of the University of the Ryukyus state, "The seas of Okinawa are home to abundant world-class biological resources. In this study, we discovered anti-leishmanial active compounds from marine sponges—treasures of the ocean—that have the potential to surpass existing drugs. Pathogens are constantly evolving, and drug resistance is an unavoidable issue. To save future patients, we are determined to continue our research in search of new 'seeds of medicine.'" They emphasized the significance of this achievement as a research outcome originating from Okinawa, while also expressing strong motivation for future work.

Overall, this work represents a major advance in addressing a long-standing global health challenge. "This research is the first step in bringing new treatment options to patients around the world and represents a significant milestone in Japan's contribution to research on neglected tropical diseases," concludes Dr. Mori-Yasumoto.

This can significantly impact global health by expanding the treatment arsenal and improving outcomes. The team's dedication to leveraging Japan's natural resources to tackle global medical issues offers renewed hope for millions suffering from leishmaniasis and potentially other devastating parasitic diseases.