Danitza Nebor, Ph.D.

Danitza Nebor, Ph.D.

Sickle cell disease (SCD) is an hemoglobinopathy caused by a mutation in the b-globin gene resulting in abnormal hemoglobin (HbS = a2bS2) in place of the normal hemoglobin A (HbA = a2b2). In patients with SCD, HbS polymerization within red blood cells (RBC) induce RBC rigidy and sickle shape that trigger the major life-threatening symptoms of SCD. The mean lifespan of patients with SCD is 36.9 years for women and 33.4 years for men.

The symptoms of the disease do not appear until 5–6 months of postnatal life. During this time, infants express high levels of fetal hemoglobin (HbF = a2g2) containing g-globin instead of the b-globin present in adult hemoglobin that provide a protective effect against HbS polymerization. Therefore, findings new means to reactivate g-globin expression in patients with SCD will delay or alleviate the disease symptoms and increase patients’ lifespan.

We have identified several genes from the mTORC1 pathway as potential negative regulators of the embryonic bh1, the mouse equivalent of the human g-globin, suggesting that a decrease of mTORC1 activity would increase the expression of the mouse bh1. Intermittent fasting and calorie restriction were shown to decrease mTORC1 activation. Therefore, we hypothesized that by regulating the mTORC1 pathway, nutritional status may regulate the level of HbF.

Being able to increase bh1 and subsequently HbF through a dietary approach may provide new nutritional guidelines accessible to most patients with SCD to alleviate disease symptoms.