Around three billion people – almost 40% of the world’s population – suffer from so-called “neglected diseases” such as tuberculosis and Dengue fever. Too little is being done in the fight against neglected diseases, which primarily occur in poor countries. Diagnostics, medication and vaccines either do not exist or are outdated and unsuitable for use in areas with poor infrastructure. Research funding for improving treatment of these diseases is also quite low. This causes the gap in equality between developed and developing countries to widen further, as these diseases lower the already low standard of living in these areas. Four NGOs (BUKO Pharma-Kampagne, the DAHW Deutsche Lepra- und Tuberkulosehilfe e.V., Brot für die Welt and Ärzte ohne Grenzen e.V.) have therefore set up the “Memento Prize for Neglected Diseases”, which is awarded for special engagement in the fight against neglected diseases. The award aims at raising awareness for activities and research in this field.
This year, the research group of Prof. Achim Hörauf from the University of Bonn and ImmunoSensation Cluster member, received the prize for their research into the development of a therapy for the neglected disease: lymphatic filariasis.
The research group has developed an innovative and effective therapeutic approach against lymphatic filariasis. About 120 million people are infected with this disease caused by the nematodes Wuchereria brancrofti, Brugia malayi and Brugia timori which are transmitted as infective third stage larvae by mosquitoes. The adult worms reside in lymphatic vessels mostly of the extremities and male genitalia and release microfilariae migrate into the blood stream. Due to the death of adult worms severe pathologies like hydrocele and lymphedema can occur in infected individuals. The anthelminthic drugs diethylcarbamazine and ivermectin, both given in combination with albendazole, are used in mass drug administration programs designed to control and eliminate filarial diseases. Apart from side effects, one major problem of all anti-filarial drugs currently in use is that they mainly only have antilarval effects and do not act against the adult worms. Since the worms can survive and breed in humans for several years, it is necessary to ensure administration of the drugs over long periods, which requires the help of intense logistical and financial support of national programs in countries with no or only developing healthcare infrastructures. Therefore, for the successful elimination of filarial infections, novel drugs are needed that also act against the adult worms. This would reliably stop filarial infection transmission, shorten the treatment periods and reduce healthcare burdens.
The group of Prof. Hörauf demonstrated that the depletion of nematode endosymbiont Wolbachia by the antibiotics doxycycline and rifampicin led to sterility and degeneration of embryos (read more here and here). Their findings show that these endosymbionts are an effective target for anti-filarial therapy. However, doxycycline and rifampicin are not eligible for mass drug administration, only for monitored treatment by a physician. First, both antibiotics have to be administered daily for a period of several weeks. Second, children and pregnant/breast feeding women cannot be treated with doxycycline. Third, rifampicin is an essential antibiotic for the treatment of tuberculosis and its use in MDA should be restricted to resistant TB. To provide alternatives to doxycycline and rifampicin, the Hörauf group has identified a promising candidate for targeting the Wolbachia endosymbiont: corallopyronin A. This is a structurally new type of antibiotic synthesized by the myxobacterium Corallococcus coralloides and acts as a noncompetitive inhibitor of bacterial DNA-dependent RNA polymerase. In vivo, corallopyronin A depleted the endosymbiont Wolbachia resulting in impeded worm development. Anti-wolbachial based therapy with corallopyronin A has the potential for defeating filariasis and preventing the painful and disfiguring disease symptoms, and is being developed for this purpose.
(featured image from colourbox.com)
Author: Kirstin Meier