done The major drawback of ARTs is

The major drawback of ARTs is the potential of malaria parasites to escape from treatment after a few days, favoring the selection of drug-resistant parasites. This is the reason of the introduction of artemisinin-based combined therapies (ACTs) to treat malaria. These treatments are based on the association of ART that rapidly kills the parasites, and a partner drug with a prolonged done to complete the cure. The World Health Organization withdrawal of artemisinin monotherapy in malaria-endemic areas did not prevent the spread of drug resistance in South-East Asia (). While this resistance is still limited and efforts are made to contain its spread, ART use is put under surveillance (). What will be the issues of using ARTs to treat other diseases? Is it only a geographical matter: cancer treatment in the north, malaria treatment in the south? ARTs also showed μM activities against other parasites (, and ), viruses (herpes virus, hepatitis B and hepatitis C viruses) and fungi (), although clinical used in humans is mainly restricted to schistosomiasis so far. Schistosomiasis is the second most devastating parasitic disease in the world, leading to chronic and debilitating disease affecting 200 million people. Repeated prophylactic doses of ARTs dramatically reduce egg production and prevent 65–97% schistosomiasis cases. Toxoplasmosis is a serious concern during pregnancy and immunosuppression. In vitro, ARTs showed high efficacy against the parasite (), and mortality was reduced in a murine model of toxoplasmosis (). African and American trypanosomiases are severe diseases with a treatment hampered by high toxicity. Preliminary in vitro data showed that ARTs could be effective against these parasites (). Double-stranded DNA herpes viruses are very common and cause severe infections in immunocompromised patients. ARTs have shown 1–15μM in vitro activity against cytomegalovirus and a rapid virus load decrease in infected patients after hematopoietic stem cell transplantation (). Taken altogether, these recent advances open new opportunities for a broader use of ARTs in tropical and non-tropical areas to treat several infectious diseases, besides malaria.
Introduction Progression of chronic kidney disease (CKD) remains an unsolved problem in nephrology as effective drugs to slow down or even reverse CKD progression are not yet available for clinical use (Science JMECfCDaC, 2012). Because the common pathological alteration in virtually every progressive CKD is renal fibrosis, several anti-fibrotic agents are among leading candidates for CKD and have finally entered clinical testing (Tampe and Zeisberg, 2014a). However, it may still take years until new treatment regimens are approved and established for clinical practice. Current management of CKD mainly aims at treating underlying conditions and cardiovascular risk factors (Science JMECfCDaC, 2012). As CKD is commonly associated with hypertension, most prevalent pharmacological interventions include angiotensin-converting enzyme inhibitors (ACEIs), angiotensin-II receptor blockers (ARBs), beta blockers, diuretics, statins and calcium channel blockers (Science JMECfCDaC, 2012; Rayner et al., 2014). Of these, only ACEIs and ARBs have demonstrated the ability to slow progression of CKD, albeit only in patients with marked proteinuria, these classes of drugs are currently considered first-line treatments (James et al., 2014). Due to the imminent clinical need for effective anti-fibrotic therapies, identification of additional, already approved drugs with reno-protective potential would be highly desirable. In this regard, aberrant methylation of genomic DNA has emerged as a novel therapeutic target. DNA methylation in general refers to methylation of cytosine bases that are clustered in so-called CpG-islands. Methylation of CpG islands within promoter regions effectively silences expression of affected genes. While methylation of promoter CpG islands is a physiological mechanism to determine cell lineage and differentiation, aberrant promoter methylation (typically referred to as hypermethylation) and subsequent transcriptional silencing of affected genes are potent contributors to carcinogenesis. Recent studies demonstrated that aberrant promoter CpG island methylation also plays a role in renal fibrosis (and in fibrosis involving other organs as well) (Bechtel et al., 2010; Tampe et al., 2014). The importance of aberrant promoter CpG island methylation is highlighted by the effectiveness of 5′-Azacytidine, the first de-methylating agent which was approved for clinical use for patients with high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (Zeisberg and Zeisberg, 2013). With regard to chronic kidney disease, administration of 5′-Azacytidine ameliorated fibrosis in several models of experimental chronic kidney injury (Bechtel et al., 2010). 5′-Azacytidine is a broad de-methylating agent which – as a cytidine analog – inhibits DNA methyltransferase 1 (DNMT1) and is incorporated into the DNA of dividing cells prompting DNA repair and replacement of methylated CpGs with naked cytosine (Foulks et al., 2012; Tampe and Zeisberg, 2014b; Tampe and Zeisberg, 2012). Due to DNA-incorporation, 5′-Azacytidine and its derivate 5′-Aza-2′-Deoxycytidine have considerable cytotoxicity in addition to their unspecific de-methylating activity. Hence, more specific normalization of aberrant hypermethylation without incorporation of potentially toxic nucleotide analogs would be much more attractive.