Testing SIROLIMUS in Beta-thalassemia Transfusion Dependent Patients

Summary

Beta-thalassemias are hereditary blood disorders caused by reduced or absent synthesis of hemoglobin beta chains, with variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Treatment is symptomatic and thalassemia is a major unmet medical need. Survival is increased, even in patients needing transfusions, in comparison with a few years ago, but the quality of life is poor for many patients. In some patients, an anomalous expression of gamma-globin genes has been observed, with a consequent rise in Fetal Hemoglobin levels. The patients displaying a clinical phenotype known as Hereditary Persistence of Fetal Hemoglobin (HPFH) exhibit a positive clinical status. To mimick HPFH, several compounds able to induce expression of fetal hemoglobins (HbF) have been evaluated. Within this framework, sirolimus is particularly interesting as an inducer of HbF. It has been used for many years for different indications and the available preclinical evidence warrant the start of a clinical development plan in thalassemia. The investigators propose a clinical trial in beta-thalassemia patients, designed to evaluate the effect of sirolimus on several parameters related to red blood cell status and to the level of HbF in particular, as a first step for the full clinical development in this new indication.

Timeline

Start

2019-06-27

Primary completion

2022-04-30

Completion

2022-04-30

Publications

• Results Zuccato C, Cosenza LC, Zurlo M, Gasparello J, Papi C, D'Aversa E, Breveglieri G, Lampronti I, Finotti A, Borgatti M, Scapoli C, Stievano A, Fortini M, Ramazzotti E, Marchetti N, Prosdocimi M, Gamberini MR, Gambari R. Expression of gamma-globin genes in beta-thalassemia patients treated with sirolimus: results from a pilot clinical trial (Sirthalaclin). Ther Adv Hematol. 2022 Jun 21;13:20406207221100648. doi: 10.1177/20406207221100648. eCollection 2022.
• Zurlo M, Finotti A, Gamberini MR, Gambari R. Co-Induction of ULK-1 and AHSP mRNAs in Erythroid Precursor Cells Isolated From a Sirolimus-Treated beta-Thalassemia Patient: A Case Report Study. Br J Biomed Sci. 2025 Jun 27;82:14311. doi: 10.3389/bjbs.2025.14311. eCollection 2025.
• Zurlo M, Nicoli F, Proietto D, Dallan B, Zuccato C, Cosenza LC, Gasparello J, Papi C, d'Aversa E, Borgatti M, Scapoli C, Finotti A, Gambari R. Effects of Sirolimus treatment on patients with beta-Thalassemia: Lymphocyte immunophenotype and biological activity of memory CD4+ and CD8+ T cells. J Cell Mol Med. 2023 Feb;27(3):353-364. doi: 10.1111/jcmm.17655. Epub 2023 Jan 10.

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