Dr. Kenneth M. Pfarr      
kenneth.pfarr @ ukbonn.de
+49  (0)228 287 -11207                                
© UKB /J. F. Saba

The filarial nematodes Wuchereria bancrofti, Brugia malayi and Onchocerca volvulus are round worms that infect humans and cause the diseases lymphatic filariasis (lymphedema and hydrocele) and onchocerciasis (river blindness). In 2017, 56 million people were infected with Wuchereria bancrofti or Brugia malayi, responsible for 1.3 million disability-adjusted life years (DALYs). For onchocerciasis the 2017 count was ~21 million cases responsible for 1.3 million DALYs. Current drugs used to interrupt the transmission of these worms to uninfected persons, while very effective at killing the first stage larvae, require several years of annual administration (5-15 years). Additionally, there is evidence for decreased efficacy of these drugs in several foci. 

These nematodes contain essential, obligate endosymbiotic bacteria of the genus Wolbachia. Using tetracyclines or rifampicin, Wolbachia can be depleted from worms in infected animal models of filariasis and human patients. Worms that have been depleted of their endosymbionts are no longer to develop. In adult female worms, depletion of Wolbachia results in a permanent block in oogenesis and embryogenesis. With our partners in Cameroon, Ghana, India, Indonesia and Tanzania, have shown that depletion of the endobacteria from filarial nematodes results in death of the adult worms at the site of infection. Because of these spectacular effects, Wolbachia are targets for controlling filarial infections. However, the current antibiotics require long regimens of daily treatment (at least 3 weeks) to achieve the anti-wolbachial effects. Newer drugs with shorter treatment times are needed to eliminate these infections by 2030 as targeted the WHO Road Map for Neglected Tropical Diseases to fulfill the United Nations Sustainable Development Goals.

My group is helping to attain the goal of eliminating these diseases by developing the natural product Corallopyronin A (CorA) as an alternative to tetracyclines or rifampicin. This natural product of Myxobacteria has a novel mode of action and has good activity against Wolbachia in vitro and in vivo. To register CorA for use in humans, we, together with our colleagues Prof. Dr. Marc Hübner and Dr. med. Ute Klarmann-Schulz from the IMMIP, are part of the German Center for Infection Research (DZIF). With this German-wide network of research institutes, we are progressing CorA through preclinical development to first-in-human trials.

To better understand Wolbachia, my group is also investigating how the endobacteria respond at the cellular level to antibiotics that disrupt cell wall biosynthesis. This information will helps understand this essential process in Wolbachia and possibly provide new targets for novel antibiotic discovery. Furthermore, we are also deciphering the genetic basis for the development of lymphatic filariasis disease manifestations (lymphedema and hydrocele). By understanding this process, we hope to discover and develop new interventions that can halt or even reverse disease progression in persons who are afflicted by lymphatic filariasis, i.e. morbidity management beyond hygiene or doxycycline treatment.

Persons interested in doing their practical, Bachelor or Masters work in our lab should send their CV and academic transcripts to Dr. Kenneth Pfarr:  kenneth.pfarr @ ukbonn.de

Funding:

• Bundesministerium für Bildung und Forschung (BMBF): Naturstoffmedizin: Präklinische Entwicklung von Corallopyronin A, einem Antibiotikum mit Wirkungen gegen würmer, sexuell übertragbare lnfektionen (STls) und Staphylokokken (Corals) - Nicht-GLP präklinischeklinische Studien"
• European Research Council https://cordis.europa.eu/project/id/671055
• European Commission Horizon 2020 "HELP Consortium":  HELP,  https://eliminateworms.org/
• Deutsche Forschungsgemeinschaft (DFG, TRR 261/1) https://trr261.de/
• Deutschen Zentrum für Infektionsforschung (DZIF): Corallopyronin A, TTU 09.822 and 09.914, TTU 09.816
• United States Agency for International Development ( USAID): Onchocerciasis LAMP assay to optimize diagnostics and sampling strategies for low-prevalence settings in Cameroon

• European and Developing Countries Clinical Trials Partnership (EDCTP) : MiniMox consortium: the project is funded for the bench-top development work, GMP-grade manufacturing of a selected formulation for the clinical trial and development of an enhanced population pharmacokinetic model of moxidectin in children and adults.

Team Members: