Cardiometabolic disease is a collection of disorders that include connected health problems affecting the circulatory system and metabolic processes. These disorders are major contributors to several of the top causes of death in the United States—including stroke, diabetes, heart disease and chronic liver disease. Doctors like Charles V. Pollack, MD, have treated cardiometabolic disorders in the past with daily medications or regular injections. But in recent years, small interfering RNA (siRNA) medicines have opened the way for alternative treatments.
siRNA can interfere with the creation of disease-driving proteins, and the effects of a single dose can potentially last for several months. From this base, researchers and scientists can develop more reliable and less burdensome medications with the potential to better prevent strokes, heart attacks, and other complications.
Conventional drugs aimed at disease-driving proteins target those already moving through the bloodstream. siRNA therapies, meanwhile, disrupt the body’s production of these proteins by silencing the genetic instructions responsible for the process. For cardiometabolic diseases, these treatments target the messenger RNA for disease-driving proteins in the liver, an organ associated with numerous cardiometabolic risk factors. siRNA reduces the amount of required messenger RNA, which causes the body to make these proteins in lesser amounts.
This approach to cardiometabolic medicine yields many benefits for patients, including the potential for meaningful and sustained decreases in LDL cholesterol, triglycerides, and other risk markers. And the fact that an injection is needed every few months might lead to better adherence by patients, a frequent problem with daily pill regimens. The precision of siRNA treatments in targeting specific proteins also lowers the possibility of the drug binding to non-target proteins, molecules, or sites, an issue with less selective treatments less targeted treatments. Additionally, researchers can leverage siRNA medicines’ ability to target proteins that traditional drugs cannot to explore therapeutic possibilities beyond the usual pathways involving glucose and cholesterol. Altogether, siRNA provides a proactive risk modification strategy, allowing clinicians to move away from reactive forms of care.
siRNA’s promising potential is evident in early clinical programs, which have demonstrated success in safely addressing biomarkers correlating with cardiovascular events. Researchers are now broadening their scope to other cardiometabolic arenas, expanding treatment targets from lipids to sources of inflammation, coagulation, atherosclerosis, heart failure, and kidney disease. This may lead to the development of therapies that allow the simultaneous management of multiple interconnected risk factors via one or two siRNA injections. In addition to population level improvements in long-term patient outcomes, such strategies may lighten the burden on pharmacies and clinics.
Although researchers have made significant progress, physicians like Charles V. Pollack, MD, remind investigators that translating molecular breakthroughs to practical and scalable patient treatments relies on several factors. First, cardiometabolic medication development with siRNAs requires the merging of clinical pharmacology, molecular biology, and real-world cardiometabolic medicine. Investigators also need to figure out the right proteins to target and develop dose schedules that fit with patients’ busy lives. And then, too, they have to design clinical studies to look at patient-centered outcomes and decrease long-term events, and make sure long-acting effects are safe and reversible.