In Pursuit of Precision

Research Nurse Coordinator Danielle Kellner, MSN, RN-BC, readies an infusion for the first patient to receive a new gene therapy for hypertrophic cardiomyopathy. | Photo: Shawn Green

You can have hypertrophic cardiomyopathy (HCM) without even knowing it. This complex heart disease affects an estimated 1 in 500 people. Many of them go undiagnosed until HCM has progressed. Most people with the disease live normal lives, although it can be fatal. Among people under the age of 30, HCM is the leading cause of sudden cardiac death. 

“The simplest way I explain HCM to patients is this: The heart muscle is thickened dramatically out of proportion,” says Milind Desai, MD, MBA, Director of the Hypertrophic Cardiomyopathy Center and Vice Chair of Education in the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute. He holds the Haslam Family Endowed Chair in Cardiovascular Medicine. 

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Dr. Milind Desai

HCM may cause changes to the mitral valve, which regulates blood flow between the left chambers of the heart, and stiffness in the left ventricle, the pumphouse that sends blood through the aortic valve to the rest of the body. The disease is categorized as obstructive or nonobstructive, depending on if it impedes blood flow. 

Until recently, HCM typically was treated with medications developed for other diseases, such as beta-blockers. Some cases may have necessitated invasive procedures such as alcohol septal ablation, which entails injecting alcohol through a catheter to shrink the thickened tissue. 

“There was a need,” Dr. Desai says, “to develop precision medicines that work specifically on HCM.” 

In 2022, the FDA approved mavacamten, the only disease-specific medication for obstructive HCM. A clinical trial led by Cleveland Clinic found that the drug significantly reduced the need for invasive procedures. 

In 2023, for the first time anywhere, Cleveland Clinic infused the new TN-201 gene therapy in a patient with nonobstructive HCM as part of a multi-center clinical trial. A one-time dose is designed to deliver a working gene to the heart muscle in hopes of reversing the disease by restoring normal levels of a protein whose mutations are the most common genetic cause of HCM. 

Dr. Desai has served as an investigator on both trials. (He is a paid consultant for Bristol Myers Squibb and Tenaya Therapeutics, which are developing mavacamten and TN-201, respectively.) 

As more precise treatments for HCM become available, improved diagnostic tools will be imperative, Dr. Desai says. He foresees integrating AI to identify electrocardiogram patterns that could be harbingers of HCM. To this end, datasets that reflect a diverse population of patients will be key. 

For Dr. Desai, upping our game against HCM is more than a matter of medicine. It’s personal. 

“I had a close friend who died of HCM,” he says. “Then again, for me, every patient is a personal connection.” ♥