Corallopyronin A: A new antibiotic against worm infections
In 2009, Prof. Achim Hörauf and his team at the University Hospital Bonn discovered that the natural substance Corallopyronin A is effective against filarial worms. Infections with these worms can lead to river blindness and, if left untreated, also to so-called elephantiasis—a dreaded disease in which body parts are greatly enlarged. Researchers at the DZIF are now developing the substance into a drug. The production process for a high-quality corallopyronin A according to pharmaceutical standards (GMP) has been established. Translational research is currently in the final phase of preclinical testing, and the first clinical trial (phase I) is planned for 2025/2026.
Background
More than 21 million people in Africa are infected with the threadworm Onchocerca volvulus, the parasite that causes river blindness. About one in ten of those affected goes blind. What is needed are active agents that kill the long-lived adult worms. In Corallopyronin A, Achim Hörauf's scientists have found an active ingredient that can do just that. Initially, it does not destroy the worms themselves, but the bacteria that live in the worms as symbionts. However, since the bacteria are necessary for the worms’ survival, they also die in the second step.
In addition to these bacteria in nematodes, the pathogens causing Tsutsugamushi fever, (see publication) including bush typhoid, as well as Chlamydia, have been proven to be sensitive to Corallopyronin A. The scientists see corallopyronins as a promising substance class for the development of antibacterial therapeutics for the treatment of sexually transmitted infections and resistant bacteria.
Development
Corallopyronin A, which originates from an environmental bacterium, was already identified by scientists at the Helmholtz Centre for Infection Research (HZI) in the 1980s as an effective antibiotic against staphylococci. When Achim Hörauf's team at the University of Bonn then discovered its effectiveness against filariae, which have devastating consequences for those affected, particularly in Africa and other tropical regions, scientists at the DZIF took a closer look at the substance for an application. Translational research is currently in the final phase of preclinical testing of Corallopyronin A.
In collaboration with the HZI, a biotechnological process has already been established to produce the substance in sufficient concentration and purity for toxicity testing (see publications on this topic from 2017 and 2019).
In 2021, a contract manufacturer was found for the large scale production process: the Belgian company BBEPP (Bio Base Europe Pilot Plant) is taking over the first part of the fermentative production process. The purification to 95 per cent pure active ingredient will be carried out by the working group of Marc Stadler, HZI, within in DZIF. The German contract manufacturer Phyton Biotech is responsible for the production of CorA under GMP conditions.
Partners
- University Hospital Bonn (more information on the project at https://www.microbiology-bonn.de/en)
- HZI
- Incubator for Antibacterial Therapies in Europe (INCATE)
- Drug for Neglected Diseases initiative (DNDi)
- DZIF
- Bio Base Europe Pilot Plant (BBEPP)
- Phyton Biotech