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

Research conducted in the United States is evaluating propranolol in preclinical models of SCD-related heart disease.

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

Ankit A. Desai, MD, an associate professor of medicine at The Ohio State University’s Krannert Cardiovascular Research Center (KCVRC), is the lead researcher of the study and was awarded the grant from the U.S. Department of Defense.

An assessment of the efficacy of propranolol – a medication approved for the treatment of high blood pressure – will be conducted in preclinical models of SCD by the researchers.

As a result of evaluating a therapeutic that has already been used by millions of people for other diseases, KCVRC’s cardiopulmonary research program leader, Desai, a cardiologist at the medical school and head of the program, said in a university press release that it may accelerate the potential use of the therapy for sickle cell patients more rapidly. In a bid to close a health care gap, this grant will enable us to study the impact of heart injury, as well as rhythm disturbances in preclinical models of sickle cell disease. The study aims to raise awareness and funding for a disease that is underrepresented and underrecognized.

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Red blood cells with sickle-shaped clotting (SCD) develop an atypical shape that makes them more sticky and inflexible. SCD is a genetic disease. Patients run the risk of serious side effects, such as cardiomyopathy, a heart ailment where the heart’s capacity to pump blood is compromised by muscle hypertrophy. Furthermore, oxidative stress, a form of cellular damage, is more likely to occur in SCD patients, and this might result in persistent inflammation.

Patients with heart disease may be at risk for deadly rhythm disturbances.

Drugs
Patients with heart disease may be at risk for deadly rhythm disturbances.

According to Desai, “cardiomyopathy or heart damage can predispose patients to ventricular tachycardia, a fatal rhythm disturbance.” “We think that inflammation is a major factor in both the development of this damaged heart and its aggravation.”

R-propranolol and S-propranolol are the two chemical molecules that combine to form propranolol, which is marketed under various names, including Inderal. As an active beta blocker, s-propranolol lowers the force of heart contractions and slows down the heart rate, which facilitates the pumping of blood. Comparable in nature, but lacking a potent beta blocker effect, is r-propranolol.

According to Rohan Dharma Kumar, PhD, executive director of the KCVRC, “new therapies are being explored, but cleverly repurposed drugs that have already had human exposure with strong safety profile, like 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.”

The toxicity of R-propranolol will be evaluated by the researchers prior to its use in a clinical trial. Bum-Rak Choi, PhD, an associate professor of medicine at Rhode Island Hospital and Brown University, will collaborate on the study. The group will work together to examine data regarding the emergence of lethal arrhythmias in people with sickle cell disease.

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

 

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