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• W4285191760 endingPage "204062072211006" @default.
• W4285191760 startingPage "204062072211006" @default.
• W4285191760 abstract "Introduction: β-thalassemia is caused by autosomal mutations in the β-globin gene, which induce the absence or low-level synthesis of β-globin in erythroid cells. It is widely accepted that a high production of fetal hemoglobin (HbF) is beneficial for patients with β-thalassemia. Sirolimus, also known as rapamycin, is a lipophilic macrolide isolated from a strain of Streptomyces hygroscopicus that serves as a strong HbF inducer in vitro and in vivo. In this study, we report biochemical, molecular, and clinical results of a sirolimus-based NCT03877809 clinical trial (a personalized medicine approach for β-thalassemia transfusion-dependent patients: testing sirolimus in a first pilot clinical trial, Sirthalaclin). Methods: Accumulation of γ-globin mRNA was analyzed using reverse-transcription quantitative polymerase chain reaction (PCR), while the hemoglobin pattern was analyzed using high-performance liquid chromatography (HPLC). The immunophenotype was analyzed using a fluorescence-activated cell sorter (FACS), with antibodies against CD3, CD4, CD8, CD14, CD19, CD25 (for analysis of peripheral blood mononuclear cells), or CD71 and CD235a (for analysis of in vitro cultured erythroid precursors). Results: The results were obtained in eight patients with the β + /β + and β + /β 0 genotypes, who were treated with a starting dosage of 1 mg/day sirolimus for 24–48 weeks. The first finding of this study was that the expression of γ-globin mRNA increased in the blood and erythroid precursor cells isolated from β-thalassemia patients treated with low-dose sirolimus. This trial also led to the important finding that sirolimus influences erythropoiesis and reduces biochemical markers associated with ineffective erythropoiesis (excess free α-globin chains, bilirubin, soluble transferrin receptor, and ferritin). A decrease in the transfusion demand index was observed in most (7/8) of the patients. The drug was well tolerated, with minor effects on the immunophenotype, and an only side effect of frequently occurring stomatitis. Conclusion: The data obtained indicate that low doses of sirolimus modify hematopoiesis and induce increased expression of γ-globin genes in a subset of patients with β-thalassemia. Further clinical trials are warranted, possibly including testing of the drug in patients with less severe forms of the disease and exploring combination therapies." @default.
• W4285191760 created "2022-07-14" @default.
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• W4285191760 date "2022-01-01" @default.
• W4285191760 modified "2023-09-30" @default.
• W4285191760 title "Expression of γ-globin genes in β-thalassemia patients treated with sirolimus: results from a pilot clinical trial (Sirthalaclin)" @default.
• W4285191760 cites W1075075767 @default.
• W4285191760 cites W1588559777 @default.
• W4285191760 cites W1598569053 @default.
• W4285191760 cites W1605787076 @default.
• W4285191760 cites W1678460261 @default.
• W4285191760 cites W1799423166 @default.
• W4285191760 cites W1840928693 @default.
• W4285191760 cites W1971500497 @default.
• W4285191760 cites W1971896388 @default.
• W4285191760 cites W1972735584 @default.
• W4285191760 cites W1974088603 @default.
• W4285191760 cites W1990174512 @default.
• W4285191760 cites W1994566624 @default.
• W4285191760 cites W2000988825 @default.
• W4285191760 cites W2001926054 @default.
• W4285191760 cites W2002870649 @default.
• W4285191760 cites W2011088013 @default.
• W4285191760 cites W2012661184 @default.
• W4285191760 cites W2019481341 @default.
• W4285191760 cites W2022850278 @default.
• W4285191760 cites W2038401835 @default.
• W4285191760 cites W2045293297 @default.
• W4285191760 cites W2050934806 @default.
• W4285191760 cites W2052657961 @default.
• W4285191760 cites W2060102731 @default.
• W4285191760 cites W2064545896 @default.
• W4285191760 cites W2064631448 @default.
• W4285191760 cites W2093675013 @default.
• W4285191760 cites W2096035113 @default.
• W4285191760 cites W2101474649 @default.
• W4285191760 cites W2107441799 @default.
• W4285191760 cites W2111503294 @default.
• W4285191760 cites W2116767791 @default.
• W4285191760 cites W2117461991 @default.
• W4285191760 cites W2126494201 @default.
• W4285191760 cites W2130887575 @default.
• W4285191760 cites W2138129102 @default.
• W4285191760 cites W2146489763 @default.
• W4285191760 cites W2148644941 @default.
• W4285191760 cites W2149623095 @default.
• W4285191760 cites W2155829072 @default.
• W4285191760 cites W2156962791 @default.
• W4285191760 cites W2159329007 @default.
• W4285191760 cites W2161933079 @default.
• W4285191760 cites W2166140328 @default.
• W4285191760 cites W2167575052 @default.
• W4285191760 cites W2195783331 @default.
• W4285191760 cites W2290269515 @default.
• W4285191760 cites W2330248283 @default.
• W4285191760 cites W2335456398 @default.
• W4285191760 cites W2416285135 @default.
• W4285191760 cites W2442729740 @default.
• W4285191760 cites W2469222194 @default.
• W4285191760 cites W2486983651 @default.
• W4285191760 cites W2534656414 @default.
• W4285191760 cites W2548645120 @default.
• W4285191760 cites W2561943186 @default.
• W4285191760 cites W2587847550 @default.
• W4285191760 cites W2593213084 @default.
• W4285191760 cites W2604230568 @default.
• W4285191760 cites W2605876078 @default.
• W4285191760 cites W2783408121 @default.
• W4285191760 cites W2793205487 @default.
• W4285191760 cites W2800270039 @default.
• W4285191760 cites W2801952734 @default.
• W4285191760 cites W2807016251 @default.
• W4285191760 cites W2835234069 @default.
• W4285191760 cites W2900131897 @default.
• W4285191760 cites W2908907368 @default.
• W4285191760 cites W2922112864 @default.
• W4285191760 cites W2947183183 @default.
• W4285191760 cites W2969547591 @default.
• W4285191760 cites W2969792377 @default.
• W4285191760 cites W2979629052 @default.
• W4285191760 cites W2982780745 @default.
• W4285191760 cites W2983573843 @default.

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