EN

Country
Germany

Affiliation
Bonn University Medical Center

Position
Director, Institute for Medical Microbiology, Immunology and Parasitology
Coordinator, Bonn-Cologne site of the German Center for Infection Research (DZIF)

Address
Institute for Medical Microbiology, Immunology and Parasitology
University Medical Center Bonn
Sigmund-Freud-Str. 25, Building 63, 53127 Bonn, Germany

Phone
+49 228 287 15673

Achim.Hoerauf@ukbonn.de

Webpage

Background and expertise of the representative

Achim Hoerauf is full Professor of Microbiology and Parasitology and Director of the Institute for Medical Microbiology, Immunology and Parasitology (http://www.microbiology-bonn.de/immip/) at the Bonn University Medical Center. After earning his MD in clinical immunology at the University of Erlangen in 1989, he was a fellow of Medical Microbiology and Infection Epidemiology in Hamburg, where he completed his habilitation (Docent)in 1998. After heading the Department of Helminthology at the Bernhard Nocht Institute for Tropical Medicine, Hamburg, in 2003 he was appointed to full Professor (C4) at the University of Bonn and became director of the Institute for Medical Microbiology, Immunology and Parasitology (IMMIP). Since 2013, he is coordinator of the Bonn-Cologne site of the German Center for Infection Research (www.DZIF.de/en) funded by the German Federal Ministry for Education and Research. DZIF’s mission is translational infection research to develop new diagnostics, preventatives and therapeutics for treating infectious diseases. He helped form the German Network against Neglected Tropical Diseases (www.DNTDs.de) and has been its chair since May 2017.

Achim Hoerauf is internationally renowned for his work in tropical medicine, specifically for pioneering a new drug treatment for nematode infections that cause filariasis, lymphatic filariasis (elephantiasis) and onchocerciasis (river blindness), a group neglected tropical diseases targeted for elimination by the WHO Sustainable Development Goals. The new treatment exploits the symbiosis between the filarial nematodes and their bacterial endosymbionts called Wolbachia that are susceptible to several classes of antibiotics. The feasibility of delivering a safe macrofilaricidal drug sparked the development of macrofilaricidal research programmes by the Gates Foundation and Drugs for Neglected Diseases initiative (DNDi). He has collaborated with key African scientists on filariasis for nearly 20 years, acting as PI on numerous clinical trials funded by the BMBF, EU, Volkswagen Foundation, and several grants from the Bill and Melinda Gates Foundation.

His group found Corallopyronin A (CorA), which is an active antibiotic against human filariasis and heartworm disease targeting endosymbiotic Wolbachia bacteria (USA patents US 9168244 B2 and US 9687470 B2, and EU patent EP 2704708 B1). Development of CorA for use in humans is a showcase project within DZIF. Late preclinical development, GMP-toxicity and other enabling studies, will be performed over the next 2 years and filing with the German agency BfArM for clinical phase 1 is planned for 2021. The project has received a positive response from the first formal scientific advice in June 2018.

CorA is also active against multi-resistant Staphylococcusaureus, antibiotic-resistant gonococci and Chlamydiae. Thus, CorA is, in principle, suitable for these indications. Sexually transmitted infections are the #2 key topic of the Global Antibiotic Research and Development Partnership (www.GARDP.org) STIs and multi-resistant S. aureus infections are on the WHO’s Priority Pathogens List (PPL) for R&D of New Antibiotics. Additional research is needed to define CorA indications and alignment with TPP, etc.

Organisation profile

The Bonn University Medical Center is composed of 32 clinics and 25 institutes with over 8000 medical, scientific and support staff. A key focus of research at the Medical Center is immunology and infection, and success in these areas has resulted in the Medical Center being selected as a DFG Cluster of Excellence (www.ImmunoSensation.de) focusing on connecting immunology to other systems and understanding the immune sensory system to human health and disease, and being selected as a DZIF research site with over 20 projects in translational infection research to develop new diagnostics, preventatives and therapies to treat infectious diseases from bacteria to parasites to viruses. The DZIF Bonn-Cologne site is coordinated by IMMIP. The medical faculty has made key strategic decisions to further strengthen and support research in immunology and infection. The IMMIP is the central infectious diseases lab of the Medical Center, processing more than 120,000 samples per year. The IMMIP is a leader in filarial research, having conducted many phase 2a trials in Ghana and Cameroon to translate anti-wolbachial therapy as a treatment for filarial infections. The IMMIP has coordinated several European Union and NGO funded trials in collaboration with the Kumasi Centre for Collaborative Research at the University of Kumasi in Ghana, the Research Foundation in Tropical Diseases and the Ministry of Scientific Research and Innovation in Cameroon, and the National Institute of Medical Research in Tanzania. The IMMIP is an active partner with DNDi, Bill & Melinda Gates Foundation and industry (e.g. Celgene, Janssen and Bayer) for in vivo pre-clinical testing and the planning and running of clinical trials of new antifilarial compounds.

Prof. Dr. Hoerauf and his team (Dr. Pfarr and Dr. Hübner) are experts in filarial nematode infections (human infections and animal models), both basic and applied science. They are currently involved in preclinical and clinical drug development for filarial infections initiated by governmental and non-governmental organizations (WHO, DNDi, BMGF, DFG) in addition to partnerships with pharmaceutical companies. This work includes in vitro and in vivo efficacy screens as well as non-GLP and GLP preclinical studies.

Contribution to the network

One of the most exciting candidates for treating filarial infections is the natural product CorA with its efficacy against the Wolbachia endosymbionts of filarial nematodes (Schiefer et al., 2012). CorA is the only new antiwolbachial drug in development that kills the adult worms in the pre-clinical models. Thus, natural products are a key source of future novel antibiotics to provide the necessary tools for Global Health and support fulfilment of the WHO’s Sustainable Development Goals (SDGs, #3: Ensure healthy lives and promote well-being for all at all ages).

The IMMIP will contribute to the network at the discovery and preclinical developmental stages, spanning in vitro and in vivo studies, for candidate discovery and validation of antibiotics, e.g. CorA, against intracellular bacteria: Chlamydia trachomatis, Neisseria gonorrhoea, Rickettsia spp., and Wolbachia (Kock et al., 2018). As a model for obligate intracellular bacteria with a highly reduced genome (~800 proteins encoded for de novo synthesis), the in vitro and in vivo platforms will elucidate mode of action targets of antibiotics with efficacy against Gram-negative bacteria. The IMMIP will further contribute screening of candidates against its biobank of more than 3000 antibiotic resistant Gram-negative bacterial strains, including XDR isolates susceptible to only one antibiotic, a class in dire need of new therapeutics (Prof. Dr. Bierbaum (Müller…Bierbaum et al., 2018)), and 4000 methicillin resistant S. aureus (MRSA) strains, the major cause of nosocomial infections (Josten et al., 2014). In addition to the biobanked samples, IMMIP has a platform to identify bacterial kinase inhibitors and has developed a MALDI-TOF method to quickly identify MRSA strains. These contributions to the network fulfil the WHO’s Priority Pathogen List for R&D of New Antibiotics and the SDGs to eliminate infectious diseases by 2030.

We will also collaborate closely with Prof. Dr. Schneider, who holds a joint professorship with IMMIP and the Pharmaceutical Microbiology department of the University of Bonn, to elucidate the mode of actions of new antibiotics using her high-throughput platforms developed for Gram-positive and Gram-negative bacteria (Ling et al. 2015). For late pre-clinical and clinical antibiotic development, the Medical Center will contribute expertise from a DZIF junior research group (Dr. med. Klarmann-Schulz) established at the IMMIP for pre-clinical and clinical study planning and implementation that works closely with the Clinical Study Core Unit of the Medical Center to plan and conduct clinical trials in accordance with Good Clinical Practice.

Achim Hoerauf’s direct involvement in the network will provide deep links to the German Network against Neglected Tropical Diseases (he is the current chair), the Drugs for Neglected Diseases initiative and Paul Ehrlich Society to guide and support integration in established NGOs.

Overview of current research

Filariasis: neglected tropical diseases

A: Filiarial worms are transmitted as larvae by blood-feeding/biting insects to humans. In the human host, they develop into adult males and females and produce progeny. B: The infections are endemic in the Tropics and Sub-Tropics, and are a major source of poverty-related diseases. C: Infections by the filarial worms Wuchereria bancrofti, which reside in the lymph vessels,  can cause lymphedema (three stages shown from left to right). D: Infections by the filarial woms Onchocerca volvulus, which reside in nodules under the skin, can cause skin diseases and vision loss/blindness (river blindness).

Antifilarial treatment and CorA

A: Filarial worms contain intracellular bacteria (Wolbacha, red dots) that are essential for worm survival. B: Treating patients infected with filarial worms with antibiotics against the Wolbachia results in sterilization of the worms and eventual worm death. C & D: Corallopyronin A (CorA) is a natural product being developed to treat filarial infections using this anti-wolbachial principle. The antibiotics effectively removes the bacteria in vitro and is much better than the gold standard doxycycline when given to gerbils infected with filarial worms.