Repurposing drugs for the treatment and control of helminth infections
Identifieur interne : 006E63 ( Ncbi/Merge ); précédent : 006E62; suivant : 006E64Repurposing drugs for the treatment and control of helminth infections
Auteurs : Gordana Panic ; Urs Duthaler ; Benjamin Speich ; Jennifer KeiserSource :
- International Journal for Parasitology: Drugs and Drug Resistance [ 2211-3207 ] ; 2014.
Abstract
Url:
DOI: 10.1016/j.ijpddr.2014.07.002
PubMed: 25516827
PubMed Central: 4266803
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<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Parasitol Drugs Drug Resist</journal-id><journal-id journal-id-type="iso-abbrev">Int J Parasitol Drugs Drug Resist</journal-id><journal-title-group><journal-title>International Journal for Parasitology: Drugs and Drug Resistance</journal-title></journal-title-group><issn pub-type="epub">2211-3207</issn><publisher><publisher-name>Elsevier</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25516827</article-id><article-id pub-id-type="pmc">4266803</article-id><article-id pub-id-type="publisher-id">S2211-3207(14)00015-3</article-id><article-id pub-id-type="doi">10.1016/j.ijpddr.2014.07.002</article-id><article-categories><subj-group subj-group-type="heading"><subject>Invited Review</subject></subj-group></article-categories><title-group><article-title>Repurposing drugs for the treatment and control of helminth infections</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Panic</surname><given-names>Gordana</given-names></name></contrib><contrib contrib-type="author"><name><surname>Duthaler</surname><given-names>Urs</given-names></name></contrib><contrib contrib-type="author"><name><surname>Speich</surname><given-names>Benjamin</given-names></name></contrib><contrib contrib-type="author"><name><surname>Keiser</surname><given-names>Jennifer</given-names></name><email>jennifer.keiser@unibas.ch</email><xref rid="cor1" ref-type="corresp">⁎</xref></contrib></contrib-group><aff id="af005">Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland</aff><aff id="af010">University of Basel, P.O. Box, CH-4003 Basel, Switzerland</aff><author-notes><corresp id="cor1"><label>⁎</label>Corresponding author. Address: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box, CH-4002 Basel, Switzerland. Tel.: +41 61 284 8218; fax: +41 61 284 8105. <email>jennifer.keiser@unibas.ch</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>30</day><month>7</month><year>2014</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="epub"><day>30</day><month>7</month><year>2014</year></pub-date><pub-date pub-type="collection"><month>12</month><year>2014</year></pub-date><volume>4</volume><issue>3</issue><fpage>185</fpage><lpage>200</lpage><history><date date-type="received"><day>16</day><month>4</month><year>2014</year></date><date date-type="rev-recd"><day>4</day><month>7</month><year>2014</year></date><date date-type="accepted"><day>13</day><month>7</month><year>2014</year></date></history><permissions><copyright-statement>© 2014 The Authors</copyright-statement><copyright-year>2014</copyright-year><license license-type="CC BY-NC-ND" xlink:href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><license-p>This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).</license-p></license></permissions><abstract abstract-type="graphical"><title>Graphical abstract</title><fig id="f0010" position="anchor"><graphic xlink:href="fx1"></graphic></fig></abstract><abstract abstract-type="author-highlights"><title>Highlights</title><p><list list-type="simple"><list-item id="o0005"><label>•</label><p>Drug repurposing continues to be the central drug discovery strategy for helminths.</p></list-item><list-item id="o0010"><label>•</label><p>Most repurposed drugs come from veterinary medicine and known drug classes.</p></list-item><list-item id="o0015"><label>•</label><p>Only a handful of drugs have advanced clinically.</p></list-item><list-item id="o0020"><label>•</label><p>More collaborations and funding are needed to advance discoveries to the market.</p></list-item></list></p></abstract><abstract><p>Helminth infections are responsible for a considerable public health burden, yet the current drug armamentarium is small. Given the high cost of drug discovery and development, the high failure rates and the long duration to develop novel treatments, drug repurposing circumvents these obstacles by finding new uses for compounds other than those they were initially intended to treat. In the present review, we summarize <italic>in vivo</italic> and clinical trial findings testing clinical candidates and marketed drugs against schistosomes, food-borne trematodes, soil-transmitted helminths, <italic>Strongyloides stercoralis</italic>, the major human filariases lymphatic filariasis and onchocerciasis, taeniasis, neurocysticercosis and echinococcosis. While expanding the applications of broad-spectrum or veterinary anthelmintics continues to fuel alternative treatment options, antimalarials, antibiotics, antiprotozoals and anticancer agents appear to be producing fruitful results as well. The trematodes and nematodes continue to be most investigated, while cestodal drug discovery will need to be accelerated. The most clinically advanced drug candidates include the artemisinins and mefloquine against schistosomiasis, tribendimidine against liver flukes, oxantel pamoate against trichuriasis, and doxycycline against filariasis. Preclinical studies indicate a handful of promising future candidates, and are beginning to elucidate the broad-spectrum activity of some currently used anthelmintics. Challenges and opportunities are further discussed.</p></abstract><kwd-group><title>Keywords</title><kwd>Drug repurposing</kwd><kwd>Drug repositioning</kwd><kwd>Helminths</kwd><kwd>Anthelmintic</kwd><kwd>Schistosoma</kwd><kwd>Trematodes</kwd><kwd>Soil-transmitted helminths</kwd><kwd>Cestodes</kwd></kwd-group></article-meta></front><floats-group><fig id="f0005"><label>Figure 1</label><caption><p>Sources of compounds for anthelmintic repurposing. A summary of the flelds from which the repurposed drugs discussed in this review are sourced. Only successful drugs and drug candidates were included. “Extended applications” refers to drugs that were already anthelmintics but whose activity was discovered to extend to a broader range of helminth species.</p></caption><graphic xlink:href="gr1"></graphic></fig><table-wrap id="t0005" position="float"><label>Table 1</label><caption><p>Trematocidal <italic>in vivo</italic> drug candidates.</p></caption><table frame="hsides" rules="groups"><thead><tr><th></th><th></th><th></th><th colspan="2">Adult infection<hr></hr></th><th colspan="2">Juvenile infection<hr></hr></th><th></th></tr><tr><th>Parasite</th><th>Drug</th><th>Host animal</th><th>Dose (mg/kg)</th><th>WBR (%)</th><th>Dose (mg/kg)</th><th>WBR (%)</th><th>References</th></tr></thead><tbody><tr><td rowspan="18"><italic>Schistosoma mansoni</italic></td><td>Dihydroartemisinin</td><td>Mouse</td><td>3 × 200–400</td><td>60–70</td><td>3 × 200–400</td><td>89–90</td><td><xref rid="b0695" ref-type="bibr">Li et al. (2012)</xref></td></tr><tr><td rowspan="2">OZ78</td><td>Mouse</td><td>400</td><td>52</td><td>200</td><td>95</td><td><xref rid="b1155" ref-type="bibr">Xiao et al. (2007)</xref></td></tr><tr><td>Hamster</td><td>200</td><td>85</td><td>100</td><td>83</td><td><xref rid="b1155" ref-type="bibr">Xiao et al. (2007)</xref></td></tr><tr><td rowspan="2">OZ288</td><td>Mouse</td><td>400</td><td>0</td><td>200</td><td>82</td><td><xref rid="b1155" ref-type="bibr">Xiao et al. (2007)</xref></td></tr><tr><td>Hamster</td><td>200</td><td>72</td><td>100</td><td>84</td><td><xref rid="b1155" ref-type="bibr">Xiao et al. (2007)</xref></td></tr><tr><td>OZ418</td><td>Mouse</td><td>400</td><td>96</td><td>200</td><td>100</td><td><xref rid="b0610" ref-type="bibr">Keiser et al. (2012a)</xref></td></tr><tr><td>Tribendimidine</td><td>Mouse</td><td>400</td><td>0</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0555" ref-type="bibr">Keiser et al. (2007b)</xref></td></tr><tr><td>Imatinib</td><td>Mouse</td><td>3 × 1000</td><td>0</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0485" ref-type="bibr">Katz et al. (2013)</xref></td></tr><tr><td>Miltefosine</td><td>Mouse</td><td>5 × 20</td><td>95</td><td>5 × 20</td><td>76</td><td><xref rid="b0290" ref-type="bibr">Eissa et al. (2011a)</xref></td></tr><tr><td>Nilutamide</td><td>Mouse</td><td>400</td><td>85</td><td>50–400</td><td>5–36</td><td><xref rid="b0595" ref-type="bibr">Keiser et al. (2010d)</xref></td></tr><tr><td>BTP-iso</td><td>Mouse</td><td>300</td><td>55</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0300" ref-type="bibr">El Bialy et al. (2013)</xref></td></tr><tr><td>Clorsulon</td><td>Mouse</td><td>1–3 × 5</td><td>88–98</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0760" ref-type="bibr">Mossallam et al. (2007)</xref></td></tr><tr><td>Anisomycin</td><td>Mouse</td><td>100</td><td>0</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0015" ref-type="bibr">Abdulla et al. (2009)</xref></td></tr><tr><td>Lasalocid sodium</td><td>Mouse</td><td>100</td><td>41–44</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0015" ref-type="bibr">Abdulla et al. (2009)</xref></td></tr><tr><td>Diffractic acid</td><td>Mouse</td><td>10–40</td><td>0</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0015" ref-type="bibr">Abdulla et al. (2009)</xref></td></tr><tr><td>Gamboic acid</td><td>Mouse</td><td>100</td><td>0</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0015" ref-type="bibr">Abdulla et al. (2009)</xref></td></tr><tr><td>Niclosamide</td><td>Mouse</td><td>100</td><td>0</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0015" ref-type="bibr">Abdulla et al. (2009)</xref></td></tr><tr><td>Rafoxanide</td><td>Mouse</td><td>50</td><td>50–56</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0015" ref-type="bibr">Abdulla et al. (2009)</xref></td></tr><tr><td><italic>Schistosoma haematobium</italic></td><td>OZ418</td><td>Hamster</td><td>400</td><td>86</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0610" ref-type="bibr">Keiser et al. (2012a)</xref></td></tr><tr><td rowspan="4"><italic>Schistosoma japonicum</italic></td><td>Dihydroartemisinin</td><td>Mouse</td><td>300</td><td>61</td><td>300</td><td>65</td><td><xref rid="b0690" ref-type="bibr">Li et al. (2011)</xref></td></tr><tr><td rowspan="3">OZ78</td><td>Hamster</td><td>200</td><td>70–94</td><td>200</td><td>73–81</td><td><xref rid="b1170" ref-type="bibr">Xiao et al. (2011)</xref></td></tr><tr><td>Rabbit</td><td>15</td><td>423</td><td>n.d.</td><td>n.d.</td><td><xref rid="b1175" ref-type="bibr">Xiao et al. (2012)</xref></td></tr><tr><td>Mouse</td><td>200–600</td><td>67–80</td><td>400</td><td>75</td><td><xref rid="b1175" ref-type="bibr">Xiao et al. (2012)</xref></td></tr><tr><td rowspan="4"><italic>Fasciola hepatica</italic></td><td rowspan="2">OZ78</td><td>Rat</td><td>100</td><td>100</td><td>100</td><td>100</td><td><xref rid="b0535" ref-type="bibr">Keiser et al. (2006b)</xref></td></tr><tr><td>Sheep</td><td>50–100</td><td>0</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0585 b0755" ref-type="bibr">Keiser et al. (2010b), Meister et al. (2013)</xref></td></tr><tr><td>MT04</td><td>Sheep</td><td>100</td><td>92</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0755" ref-type="bibr">Meister et al. (2013)</xref></td></tr><tr><td>Tribendimidine</td><td>Rats</td><td>800</td><td>0</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0555" ref-type="bibr">Keiser et al. (2007b)</xref></td></tr><tr><td rowspan="2"><italic>Clonorchis sinensis</italic></td><td>OZ78</td><td>Rat</td><td>300</td><td>99</td><td>300</td><td>79</td><td><xref rid="b0495" ref-type="bibr">Keiser and Utzinger (2007a)</xref></td></tr><tr><td>Tribendimidine</td><td>Rat</td><td>150</td><td>98</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0555" ref-type="bibr">Keiser et al. (2007b)</xref></td></tr><tr><td rowspan="2"><italic>Opisthorchis viverrini</italic></td><td>OZ78</td><td>Hamster</td><td>600</td><td>77</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0495" ref-type="bibr">Keiser and Utzinger (2007a)</xref></td></tr><tr><td>Tribendimidine</td><td>Hamster</td><td>400</td><td>63</td><td>n.d.</td><td>n.d.</td><td><xref rid="b0555" ref-type="bibr">Keiser et al. (2007b)</xref></td></tr></tbody></table><table-wrap-foot><fn><p>WBR indicates worm burden reduction in relation to untreated control animals. n.d. denotes a lack of data.</p></fn></table-wrap-foot></table-wrap><table-wrap id="t0010" position="float"><label>Table 2</label><caption><p>Drugs tested in clinical trials against soil-transmitted helminths (<xref rid="b0680 b0335 b0970 b0885 b0005 b0460 b0960 b0425 b0150 b0910 b0880 b0170 b1195 b0475 b0240 b0030 b0125 b0330" ref-type="bibr">See below-mentioned references for further information</xref>).</p></caption><table frame="hsides" rules="groups"><tbody><tr><td><inline-graphic xlink:href="fx2.gif"></inline-graphic></td></tr></tbody></table></table-wrap><table-wrap id="t0015" position="float"><label>Table 3</label><caption><p>Drugs tested in clinical trials against the major cestodes (<italic>Taenia</italic> and <italic>Echinococcus</italic>).</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Drug</th><th>Parasite</th><th>Number of patients</th><th>Dose</th><th>Outcome</th><th>References</th></tr></thead><tbody><tr><td rowspan="3">Nitazoxanide</td><td><italic>T. saginata</italic><break></break><italic>H. nana</italic></td><td>22<break></break>18</td><td>25 mg/kg<break></break>50 mg/kg</td><td>100% CR<break></break>100% CR</td><td><xref rid="b0895" ref-type="bibr">Rossignol and Maisonneuve (1984)</xref></td></tr><tr><td><italic>T. saginata</italic></td><td>18 children<break></break>34 adults<break></break>(niclosamide and praziquantel-resistant infections)</td><td>20 mg/kg p.o. (children 5–14 years); 500 mg twice daily for 3 days p.o. (> 14 years)</td><td>98% CR</td><td><xref rid="b0675" ref-type="bibr">Lateef et al. (2008)</xref></td></tr><tr><td><italic>Echinococcus</italic> spp. (in combination with albendazole)</td><td>5</td><td>500 mg/12 hours for 3–24 months</td><td>40% improvement (2 patients improved)</td><td><xref rid="b0820" ref-type="bibr">Perez-Molina et al. (2011)</xref></td></tr><tr><td>Mepacrine (quinacrine)</td><td><italic>T. saginata</italic></td><td>86</td><td>1 g p.o. or i.g.</td><td>94%</td><td><xref rid="b0650" ref-type="bibr">Koul et al. (2000)</xref></td></tr><tr><td>Tribendimidine</td><td><italic>Taenia</italic> spp.</td><td>15</td><td>200 mg p.o. single dose (children 5–14 years) 400 mg p.o. single dose (⩾15 years)</td><td>67% CR</td><td><xref rid="b1270" ref-type="bibr">Steinmann et al. (2008)</xref></td></tr><tr><td>Paramomycin</td><td><italic>T. saginata</italic><break></break><italic>H. nana</italic></td><td>145<break></break>49</td><td>1–5 days with 30–50 mg/kg<break></break>30 mg/kg single or double dose</td><td>89–100% CR<break></break>90% CR</td><td><xref rid="b0905" ref-type="bibr">Salem and el-Allaf (1969)</xref></td></tr><tr><td>Chlorhexidine gluconate</td><td><italic>E. granulosis</italic></td><td>30</td><td>0.04% in intracystic injection</td><td>100% death of cystic protoscolices</td><td><xref rid="b1040" ref-type="bibr">Topcu et al. (2009)</xref></td></tr></tbody></table><table-wrap-foot><fn><p>p.o denotes oral treatment, i.g. denotes treatment via a nasogastric tube, CR stands for “cure rate”.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list></list><tree><noCountry><name sortKey="Duthaler, Urs" sort="Duthaler, Urs" uniqKey="Duthaler U" first="Urs" last="Duthaler">Urs Duthaler</name><name sortKey="Keiser, Jennifer" sort="Keiser, Jennifer" uniqKey="Keiser J" first="Jennifer" last="Keiser">Jennifer Keiser</name><name sortKey="Panic, Gordana" sort="Panic, Gordana" uniqKey="Panic G" first="Gordana" last="Panic">Gordana Panic</name><name sortKey="Speich, Benjamin" sort="Speich, Benjamin" uniqKey="Speich B" first="Benjamin" last="Speich">Benjamin Speich</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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