Cleveland Clinic performs first-in-human gene therapy for hypertrophic cardiomyopathy
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- The patient in this clinical trial, a 27-year-old woman, received a dose and is doing well.
October 2023, Cleveland: Cleveland Clinic has administered a new gene therapy to deliver a working gene that addresses the main cause of hypertrophic cardiomyopathy (HCM) to the world’s first patient as part of a clinical trial.
Mutations in the myosin-binding protein C3 (MYBPC3) gene are the most common genetic cause of HCM. The gene therapy is designed to deliver a working MYBPC3 gene to the heart muscle through a one-time infusion of TN-201, a first-in-class adeno-associated virus-based gene therapy. The hope is that this new gene will restore normal levels of the protein, which regulates the contraction and relaxation of heart muscle. In preclinical studies, a single dose restored normal protein levels, leading to improvement of the disease.
Hypertrophic cardiomyopathy is a complex type of heart disease that causes thickening of the heart muscle, stiffening of the left ventricle and changes to the mitral valve. It is estimated to affect between 600,000 and 1.5 million Americans, or one in 500 people, but many of these patients are not diagnosed until the disease has progressed.
The cause of hypertrophic cardiomyopathy may be unknown or attributed to genetics, high blood pressure or ageing, making it difficult to identify a high-risk population. Symptoms include chest pain, palpitations, shortness of breath, fatigue and syncope (fainting). Most people with hypertrophic cardiomyopathy have a low risk of sudden cardiac death. However, the condition is the most common cause of sudden cardiac death in people under 30.
“Our understanding of HCM has advanced, and we are excited to be part of combining that knowledge with technology such as gene therapy to advance even further,” said Milind Desai, M.D., M.B.A., director of the Hypertrophic Cardiomyopathy Center at Cleveland Clinic and vice chair of Cleveland Clinic’s Heart, Vascular & Thoracic Institute. Dr. Desai is an investigator in the phase 1b MyPeak-1 clinical trial. “We look forward to continuing to study this therapy in a patient population that is often not properly diagnosed and can suffer debilitating symptoms and sudden death.”
Currently, there is only one specific medicine to treat hypertrophic cardiomyopathy. Mavacamten, a medicine approved by the FDA in April 2022 following a trial led by Cleveland Clinic, is used to treat the obstructive form of HCM and reduce the need for invasive procedures. Surgical options include septal myectomy, in which a surgeon removes a small amount of the thickened septal wall to widen the outflow tract (the path blood takes) from the left ventricle to the aorta. Another option is alcohol septal ablation, a cardiac catheterisation procedure in which a small amount of pure alcohol is injected into the septum, causing it to shrink to a more normal size and widen the path for blood flow. However, few high-volume centres perform these procedures, which can limit patient access and require repeat interventions.
The patient in this clinical trial, a 27-year-old woman, received a dose and is doing well. The phase 1b MyPeak-1 clinical trial is a multicentre study designed to assess the safety and clinical efficacy of this one-time infusion. The trial aims to enrol at least six symptomatic adults who have been diagnosed with non-obstructive MYBPC3-associated HCM and who have implantable cardioverter defibrillators.
The trial is sponsored by Tenaya Therapeutics Inc.
Dr. Desai is a paid consultant for Tenaya Therapeutics Inc. and Bristol Myers Squibb.
About Cleveland Clinic
Cleveland Clinic is a nonprofit multispecialty academic medical centre that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based on the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States.
U.S. News & World Report consistently names Cleveland Clinic as one of the nation’s best hospitals in its annual “America’s Best Hospitals” survey. Among Cleveland Clinic’s 72,500 employees worldwide are more than 5,050 salaried physicians and researchers, and 17,800 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,500-bed health system that includes a 173-acre main campus near downtown Cleveland, 21 hospitals, more than 220 outpatient facilities, and locations in northeast Ohio; southeast Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England.
In 2021, there were 10.2 million outpatient visits, 304,000 hospital admissions and observations, and 259,000 surgeries across Cleveland Clinic’s health system. Patients came for treatment from every state and 185 countries.
Visit us at clevelandclinic.org. Follow us at twitter.com/ClevelandClinic. News and resources available at newsroom.clevelandclinic.org.
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