Nearly $1M Grant to Support Work Into Reactivating Fetal Hemoglobin

The National Heart, Lung, and Blood Institute (NHLBI) awarded nearly $1 million to Athena Starlard-Davenport, a professor at the University of Tennessee Health Science Center (UTHSC), to support work into fetal hemoglobin as a potential way of treating sickle cell disease (SCD).

“For the past 100 years, only four drugs have been approved by the FDA for the treatment of sickle cell disease,” Starlard-Davenport, PhD, said in a press release. “Those patients need more treatment options depending on their symptoms and complications.”

Her research project, “MicroRNA-based epigenetic approach to induce fetal hemoglobin,” will investigate the potential of a single microRNA (miRNA) molecule, called miRNA29b, to reactivate the production of fetal hemoglobin, the protein that carries oxygen in a developing baby but is largely lost after birth. (MicroRNAs are a special class of short RNA molecules capable of regulating gene activity.)

Fetal hemoglobin is more effective at transporting oxygen in red blood cells than the version of the protein found in adults. The mutation in the HBB gene that causes SCD results in abnormal sickle hemoglobin being produced during the first year of life, when the body switches from fetal to adult hemoglobin.

Switching back the gamma globin gene responsible for fetal hemoglobin has been shown to ease SCD symptoms and increase the number of red blood cells with this hemoglobin form.

Hydroxyurea is the only therapy, approved by the U.S. Food and Drug Administration (FDA) in 1997, that works to promote fetal hemoglobin production to address SCD symptoms.

Other therapeutic strategies for re-activating the fetal hemoglobin gene — using epigenetic modulators, such as blockers of the DNMT1 enzyme — have shown promising results but can carry off-target side effects. Epigenetic modulators influence gene activity without altering the underlying DNA sequence.

Starland-Davenport is a professor of genetics, genomics, and informatics at the UTHSC College of Medicine.

Her early work on miRNA29b won a Collaborative Research Network (CORNET) Award in 2016, for the project “Investigation of miR29 as a novel fetal hemoglobin inducer and treatment for patients with sickle cell disease.” This work was conducted in collaboration with Patricia Adams-Graves, PhD, a professor at the Diggs-Kraus Sickle Cell Clinic at Regional One Health.

The funding allowed the researchers to start testing their microRNA-based therapy approach to induce the production of fetal hemoglobin.

“The CORNET award provided funding support to collect blood samples from sickle cell patients and to test whether our miRNA therapeutic could increase levels of fetal hemoglobin in vitro in cell culture and in preclinical sickle cell models,” Starlard-Davenport said.

“My team provided preliminary results to show that miRNA29b could increase levels of fetal hemoglobin in a compatible human cell line, but we needed further preliminary data to determine what effect miRNA29b had on fetal hemoglobin induction in red blood cells from individuals with and without sickle cell disease,” she added.

The new three-year $928,317 grant from the NHLBI, a part of the National Institutes of Health (NIH), will allow the scientists to test miRNA29b in blood samples collected from SCD patients, with the long-term goal of developing a new treatment.