$3M awarded to study repurposing of blood pressure drug for SCD

US study to assess propranolol in preclinical models of SCD-linked heart disease

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A $3-million federal grant to investigate the potential of repurposing a blood pressure medication for sickle cell disease (SCD)-related cardiac disease has been awarded to researchers at Indiana University School of Medicine.

The grant from the U.S. Department of Defense was given to the study’s lead researcher Ankit A. Desai, MD, an associate professor of medicine at the university’s Krannert Cardiovascular Research Center (KCVRC).

Researchers will assess the efficacy of propranolol — an approved medication for high blood pressure — in preclinical models of SCD.

“Evaluating a therapeutic that has already been consumed by millions for other diseases could help accelerate the potential use in patients with sickle cell more quickly,” Desai, a cardiologist at the medical school and leader of KCVRC’s cardiopulmonary research program, said in a university press release. “This grant will allow us to study heart injury as well as rhythm disturbance impact in preclinical models of sickle cell disease. The study funds a disease that is underrecognized and underrepresented and supports a broader goal at closing health care gaps.”

SCD is a genetic condition in which red blood cells acquire an unusual sickle-like shape that makes them more rigid and sticky. Patients are at risk of major complications, including cardiomyopathy, a heart condition caused by the enlargement of heart muscles that impairs the ability to pump blood effectively. In addition, SCD patients have an increased susceptibility to oxidative stress — a type of cellular damage — which can lead to chronic inflammation.

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Heart damage can predispose patients to fatal rhythm disturbance

“Cardiomyopathy or heart damage can predispose patients to a fatal rhythm disturbance called ventricular tachycardia,” Desai said. “We believe that inflammation plays a key role in both, creating this injurious heart and exacerbating it.”

Propranolol (sold under the brand name Inderal, among others) is a combination of two chemical compounds, R-propranolol and S-propranolol. S-propranolol is an active beta blocker, a type of medicine that slows down the heart rate and reduces the force of heart contractions, making it easier to pump out blood. R-propranolol is a similar compound, but without a strong beta blocker activity.

“While new therapies are being explored, cleverly repurposed drugs that have already had human exposure with strong safety profile, such as R-propranolol, stand to make major headway in solving a long-standing health issue affecting the heart and cardiovascular system in the United States and abroad,” said Rohan Dharmakumar, PhD, executive director of the KCVRC.

The researchers will assess the toxicity of R-propranolol before testing it in a future clinical trial. The research will be conducted in collaboration with Bum-Rak Choi, PhD, associate professor of medicine at Rhode Island Hospital and Brown University. The team will join efforts and analyze data about the development of fatal arrhythmias in SCD patients.

“We are deeply interested in translating this potential therapeutic to patients, developing a clinical trial and trying to understand the impact [of] R-propranolol, given that propranolol appears to be well tolerated in patients otherwise,” Desai said.