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To determine if <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content> inhibition would improve anaemia in sickle cell disease (<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>), mice with <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content> were treated with the dual <jats:styled-content style=\"fixed-case\">mTORC<\/jats:styled-content>1\/2 inhibitor, <jats:styled-content style=\"fixed-case\">INK<\/jats:styled-content>128. One week after daily oral drug treatment, erythrocyte count, haemoglobin, and haematocrit were all significantly increased while reticulocyte counts were reduced. These parameters remained stable during 3\u00a0weeks of treatment. Similar effects were observed following oral treatment with the <jats:styled-content style=\"fixed-case\">mTORC<\/jats:styled-content>1 inhibitor, sirolimus. Sirolimus treatment prolonged the lifespan of sickle cell erythrocytes in circulation, reduced spleen size, and reduced renal and hepatic iron accumulation in <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content> mice. Following middle cerebral artery occlusion, stroke size was reduced in <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content> mice treated with sirolimus. In conclusion, <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content> inhibition is protective against anaemia and organ damage in a murine model of SCD.<\/jats:p>","DOI":"10.1111\/bjh.14057","type":"journal-article","created":{"date-parts":[[2016,3,31]],"date-time":"2016-03-31T22:23:19Z","timestamp":1459462999000},"page":"461-469","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["<scp>mTOR<\/scp> Inhibition improves anaemia and reduces organ damage in a murine model of sickle cell disease"],"prefix":"10.1111","volume":"174","author":[{"given":"Jintao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine University of Michigan Cardiovascular Research Center Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Cardiovascular Research Center Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Cardiovascular Research Center Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Harro","sequence":"additional","affiliation":[{"name":"Chemical Pathology University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel T.","family":"Eitzman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Cardiovascular Research Center Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,31]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"7","article-title":"Current therapy of sickle cell disease","volume":"91","author":"Aliyu Z.Y.","year":"2006","journal-title":"Haematologica"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2014.03.011"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1104964108"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002360"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1401731"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfr318"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2217\/bmm.12.71"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp778"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-2277.2007.00506.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0810584105"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61682-2"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.01.017"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0712"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.01913"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-02-0616"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-148-12-200806170-00221"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-4458"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-444455"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-549717"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-04-637702"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05083.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199807163390310"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0b013e328345213e"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1842"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5339.876"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199107043250103"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5339.873"},{"key":"e_1_2_8_29_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1001\/jama.1989.03420020120042","article-title":"Herrick's 1910 case report of sickle cell anemia. 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