Japanese researchers have discovered promising compounds in Okinawan marine sponges that could revolutionize treatment for leishmaniasis, a neglected tropical disease affecting 12 million people worldwide, with breakthrough findings published today in Marine Biotechnology journal.
The research team, led by Associate Professor Kanami Mori-Yasumoto from Tokyo University of Science’s Faculty of Pharmaceutical Sciences, isolated 10 natural compounds called onnamides from Theonella sponges collected in Manza, Okinawa, with two compounds demonstrating remarkable effectiveness against the disease-causing parasite.
Onnamide A and 6,7-dihydro-onnamide A showed potent activity against Leishmania major parasites while sparing human cells, thanks to their low toxicity and high selectivity, positioning them as highly promising compounds for new treatment development.
The discovery arrives as current leishmaniasis treatments face severe limitations. Existing drugs including antimonial compounds, amphotericin B, miltefosine, and paromomycin are hindered by high toxicity, serious side effects, prohibitive costs, and growing drug resistance across different regions.
Leishmaniasis affects approximately 12 million people across 90 countries, with 350 million more at risk of infection. The disease commonly manifests as skin sores that develop into deep ulcers, often leaving permanent facial, hand, and foot scarring that creates social stigma and psychological trauma for patients.
The research breakthrough stems from careful laboratory analysis of extracts from Theonella sponges, focusing specifically on onnamide compounds. Through systematic testing, researchers discovered that several compounds showed remarkable effectiveness against Leishmania major, a representative parasite species causing cutaneous leishmaniasis.
Most significantly, onnamide A appears to combat the parasite through a pathway distinct from amphotericin B, which typically works by interacting with ergosterol in parasite cell membranes. This discovery could guide scientists toward new treatment approaches while helping overcome existing drug resistance mechanisms.
The research team included Dr. Takahiro Jomori from University of the Ryukyus, Dr. Yasuhiro Hayashi from University of Miyazaki, Dr. Mina Yasumoto-Hirose from Tropical Technology Plus, and Dr. Junichi Tanaka from University of the Ryukyus, representing collaborative expertise across multiple Japanese institutions.
Dr. Mori-Yasumoto highlighted broader implications beyond leishmaniasis treatment. “It may also be possible to apply these compounds to other protozoan diseases, such as Chagas disease and African sleeping sickness,” she stated, emphasizing the study’s potential impact on multiple neglected tropical diseases.
The World Health Organization (WHO) has worked to reduce prices of existing leishmaniasis medicines, achieving 90% price reductions for liposomal amphotericin B and 60% for meglumine antimoniate, while Gilead Sciences donated 380,000 vials of AmBisome through WHO agreements.
However, treatment challenges persist, with WHO and the Drugs for Neglected Diseases initiative (DNDi) suggesting combination therapies of intravenous liposomal amphotericin B and oral miltefosine, though miltefosine availability remains uncertain due to frequent treatment discontinuation from side effects.
The discovery reveals onnamide G’s structure for the first time, providing new insights into the structural diversity and potential mechanisms of action within the onnamide family. This structural knowledge could accelerate development of synthetic analogs with enhanced therapeutic properties.
Scalability represents a crucial consideration for therapeutic development. Dr. Mori-Yasumoto noted that mass-production platforms for onnamide synthesis using modern culturing technology and symbiotic bacteria could ensure sustainable sources, with symbiotic bacteria offering environmentally responsible drug production strategies.
Further research continues under Japan’s Agency for Medical Research and Development (AMED) Drug Discovery Booster program, focused on transforming promising drug candidates into new medicines. Extended analyses remain necessary to establish cost-effectiveness, in vivo efficacy, and pharmacokinetics before clinical development begins.
Dr. Tanaka and Dr. Jomori emphasized the significance of leveraging Okinawa’s marine biological resources. “The seas of Okinawa are home to abundant world-class biological resources,” they stated. “We discovered anti-leishmanial active compounds from marine sponges that have the potential to surpass existing drugs.”
The researchers stressed urgency driven by pathogen evolution and inevitable drug resistance. “To save future patients, we are determined to continue our research in search of new seeds of medicine,” they declared, emphasizing commitment to addressing global health challenges through natural product research.
Recent studies have documented amphotericin B resistance in clinical isolates from patients with diffuse cutaneous leishmaniasis, particularly those coinfected with HIV who experienced unsuccessful therapeutic regimens with multiple drugs.
The marine sponge discovery represents Japan’s growing contribution to neglected tropical disease research. Dr. Mori-Yasumoto concluded that this research constitutes the first step toward bringing new treatment options to patients worldwide while establishing a significant milestone in addressing global health challenges.
Industry experts suggest that successful development of onnamide-based therapeutics could transform leishmaniasis treatment paradigms, particularly for cutaneous forms affecting vulnerable populations in tropical and subtropical regions where current treatments remain inadequate or inaccessible.
The research timeline targeting clinical development phases will determine whether these ocean-derived compounds can fulfill their therapeutic promise for millions suffering from leishmaniasis and potentially other devastating parasitic diseases across affected regions.
Source: newsghana.com.gh
