About our research group/lab
Mycetoma is an neglected tropical implementation mycosis which results in tumorous lesions on mainly the feet. It can be caused by more than 70 different micro-organisms and the true burden of mycetoma is not known. By meta-analysis and by identifying causative agents from multiple sites on the world we are contributing to the understanding on the epidemiology of mycetoma.
To understand the diversity of the causative agents and to be able to treat mycetoma, it is important to identify the causative agent as early as possible. We demonstrated that molecular assays are the best way to do this. We developed DNA extraction directly from mycetoma grains and several molecular identification tools. In close collaboration with the endemic regions we are analyzing the performance of these assays in the clinical setting.
As mentioned above, in mycetoma the causative agents organize themselves in protective structures called grains. How these grains are formed is not known. We therefore developed several grain models which we use to unravel the processes leading to grain formation.
Due to the formation of protective grains it is very difficult to treat mycetoma infections, especially those caused by fungi. We therefore developed a drug discovery pipeline in our laboratory in which we use in vitro susceptibility assays as well as Galleria mellonella grain models to determine the activity of drugs towards mycetoma causative agents. Using this pipeline we discovered that ravuconazole, the drug currently investigated in a DNDi led clinical trial in Sudan. We also use an Open Source drug discovery program called MycetOS to identify novel compounds active against mycetoma.
- Proof-of-Concept Superiority Trial of Fosravuconazole versus Itraconazole for eumycetoma in Sudan (NCT03086226).
In this DNDi sponsored international study we are one of the partners evaluating the clinical efficacy of fosravuconazole for the treatment of mycetoma patients in Sudan.
- Developing a grain model for mycetoma
In this study we study the development of grains in mycetoma. This information is used to develop grain models which can predict the efficacy of antifungal agents against mycetoma grains.
An Open Source Drug discovery program in which we test various drug libraries for efficacy against mycetoma causative agents. To assess the chemical properties needed to penetrate the mycetoma grain several analogues are prepared by collaborators all over the world.
Lim W, Melse Y, Konings M, Phat Duong H, Eadie K, Laleu B, Perry B, Todd M, Ioset J, van de Sande W. 2018. Addressing the most neglected diseases through an open research model: the discovery of the fenarimols as novel drug candidates for eumycetoma. PLoS Negl Trop Dis. 12: e0006437
Kloezen W, van Helvert-van Poppel M, Fahal A, van de Sande W. 2015. A Madurella mycetomatis grain model in Galleria mellonella larvae. PLoS Negl Trop Dis. 9: e0003926
Van de Sande W. 2013. Global burden of human mycetoma: a systematic review and meta-analysis. PLoS Negl Trop Dis 7: e2550
Prof Fahal of the Mycetoma research centre
Prof Ed Zijlstra, Jean-Robert Ioset and Ben Perry of Drugs for Neglected Diseases initiative
Prof Matthew Todd, University College London, School of Pharmacy
Funding & Grants
EUR fellowships in 2016 and 2018
NWO Aspasia premie