Rapamycin increases fetal hemoglobin and ameliorates the nociception phenotype in sickle cell mice

Improved Fetal Hemoglobin With mTOR Inhibitor–Based Immunosuppression in a Kidney Transplant Recipient With Sickle Cell Disease

“…In our patient, the use of everolimus with tacrolimus was well tolerated and effective and avoided an acute rejection. Moreover, as expected with in vitro studies , where rapamycin was associated with improved fetal hemoglobin and somatosensory function, fetal hemoglobin rate was clearly increased and the patient had reduced pain related to SCD, even though the sickle hemoglobin level was high.…”

“…The mTOR complex 1 pathway has been identified as a critical regulator of red blood cell growth and proliferation . The use of mTOR inhibitors in normal and β‐thalassemia patients has increased; in vitro, the expression of fetal hemoglobin is increased to higher levels than those obtained with hydroxyurea .…”

“…The mTOR inhibitors, such as sirolimus or everolimus, are frequently used in immunosuppressive treatments after solid organ transplantation to prevent rejection and to avoid renal dysfunction related to the use of calcineurin inhibitors or for their antiviral or antineoplastic effects . Recently, the role of mTOR inhibitors to increase hemoglobin and fetal hemoglobin levels in erythrocytes was highlighted in vitro but also in murine models of SCD .…”

Cognitive and behavior deficits in sickle cell mice are associated with profound neuropathologic changes in hippocampus and cerebellum

“…Importantly, these neuronal changes were more severe in hippocampus and more pronounced in older homozygotes than in young homozygotes and heterozygous mice. These findings raise the possibility that in Townes mice, there may be a gene dose effect and that the differing degree of sickle hemoglobin expression (Kenyon et al, 2015; Khaibullina et al, 2015) and/or disease severity and duration affect cognitive function. While the neuropathologic changes identified in SCD mice warrant further characterization, it is conceivable that the neuronal changes in hippocampus and cerebellum could at least in part explain the cognitive deficits in SCD mice.…”

Additive effect of sirolimus and hydroxycarbamide on fetal haemoglobin level in kidney transplant patients with sickle cell disease

“…While most patients tolerate and respond to HC, others do not, and the search for other agents to raise HbF is on‐going. Mechanistic/mammalian target of Rapamycin (mTOR) inhibitors were reported to increase HBG1/HBG2 mRNA (Fibach et al , ) and HbF production in human cell cultures (Pecoraro et al , ), an animal model of SCD (Khaibullina et al , ) and in one patient with SCD who was treated with HC and everolimus (Gaudre et al , ).…”