Specific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasis

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Drug resistance is complicating the treatment of parasitic diseases including African trypanosomiasis, a fatal disease if left untreated. Development of a vaccine is unlikely due to parasite antigenic variation. Current chemotherapy relies primarily on four drugs. Three of these drugs access the cell’s interior through surface transporters and resistance mechanisms are largely associated with loss-of-function mutations in the involved surface drug transporters. We reasoned that using an alternative drug entrance would circumvent parasite resistance due to mutation in a surface transporter. We have developed a drug nanocarrier that consists of polymeric nanoparticles coated with a single domain antibody that targets the trypanosome surface. This new formulation reduces the minimal curative dose and, most importantly, circumvents drug resistance in a resistant cell line as a result of mutations in the surface transporter that mediate drug uptake. This study presents a proof-of-concept of a novel technology for reversing transporter-related drug resistance with applications to other infectious diseases.

Vyšlo v časopise: Specific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasis. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004942
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004942

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