Gert-Jan Wijnant

Université Catholique de Louvain - UCLouvain | UCLouvain · Louvain Drug Research Institute (LDRI)

Objectives: Post-kala-azar-dermal leishmaniasis (PKDL) is an infectious skin disease that occurs after apparent cure from visceral leishmaniasis (VL) and causes stigmatizing lesions on the face and other exposed body parts. While the first-line drug miltefosine is typically used for 28 days to treat VL, 12 weeks of therapy is required for PKDL, hig...

As a facultative intracellular pathogen, M. tuberculosis (Mtb) is highly adapted to evading antibacterial mechanisms in phagocytic cells. Both the macrophage and pathogen experience transcriptional and metabolic changes from the onset of phagocytosis. To account for this interaction in the assessment of intracellular drug susceptibility, we allowed...

Leishmaniasis is a tropical infectious disease caused by the protozoan Leishmania parasite. The disease is transmitted by female sand flies and, depending on the infecting parasite species, causes either cutaneous (stigmatizing skin lesions), mucocutaneous (destruction of mucous membranes of nose, mouth and throat) or visceral disease (a potentiall...

SQ109 is a novel well-tolerated drug candidate in clinical development for the treatment of drug-resistant tuberculosis (TB). It is the only inhibitor of the MmpL3 mycolic acid transporter in clinical development. No SQ109-resistant mutant has been directly isolated thus far in vitro, in mice, or in patients, which is tentatively attributed to its...

The nitroimidazole DNDI-0690 is a clinical drug candidate for visceral leishmaniasis (VL) that also shows potent in vitro and in vivo activity against cutaneous leishmaniasis (CL). To support further development of this compound into a patient-friendly oral or topical formulation for CL, we investigated the free drug exposure at the dermal site of...

Objectives: Drugs for Neglected Diseases initiative (DNDi) has identified three chemical lead series, the nitroimidazoles, benzoxaboroles and aminopyrazoles, as innovative treatments for visceral leishmaniasis. The leads discovered using phenotypic screening, were optimised following disease- and compound-specific criteria. Several leads of each s...

Fungisome® (F), a liposomal amphotericin B (AmB) product, is marketed in India as a safe and effective therapeutic for the parasitic infection visceral leishmaniasis. Its potential in the treatment of cutaneous leishmaniasis (CL), a disfiguring form of the disease affecting the skin, is currently unknown. Here, we report the evaluation of the effic...

Disfiguring skin lesions caused by several species of the Leishmania parasite characterize cutaneous leishmaniasis (CL). Successful treatment of CL with intravenous (IV) liposomal amphotericin B (LAmB) relies on the presence of adequate antibiotic concentrations at the dermal site of infection within the inflamed skin. Here, we have investigated th...

AmBisome® (LAmB), a liposomal formulation of amphotericin B (AmB), is a second-line treatment for the parasitic skin disease cutaneous leishmaniasis (CL). Little is known about its tissue distribution and pharmacodynamics to inform clinical use in CL. Here, we compared the skin pharmacokinetics of LAmB with Fungizone® (DAmB), the deoxycholate form...

The 4-aminoquinoline chloroquine (CQ) is clinically used in combination with doxycycline to cure chronic Q-fever, as it enhances the activity of the antibiotic against the causative Coxiella burnetii bacteria residing within macrophage phagolysosomes. As there is a similar cellular host-pathogen biology for Leishmania parasites, this study aimed to...