New gene therapy may help protect the hearts of patients with Friedreich's ataxia
A first-in-human gene therapy trial may offer new hope for patients with Friedreich's ataxia (FA), a rare inherited disorder in which cardiomyopathy is the leading cause of death. There are no current treatments for FA cardiomyopathy.
The late-breaking results were presented at ACC.26, the annual conference of the American College of Cardiology. The data suggest an experimental treatment could slow or even halt the cardiac decline that proves fatal for most patients. Cardiovascular Business spoke with presenter Ronald Crystal, MD, chair of the department of genetic medicine at Weill Cornell Medicine, to find out more.
Crystal explained that FA is an autosomal recessive disease that affects both the nervous system and the heart, typically emerging in childhood or adolescence. While neurological symptoms can be debilitating, cardiac complications account for up to 70% of deaths, making the heart the primary target for therapeutic intervention.
Crystal and colleagues tested an investigational gene therapy, AAVrh.10hFXN (LX2006), designed to deliver a functional copy of the frataxin gene, which is deficient in FA, directly into heart cells using a viral vector. Crystal explained that frataxin plays a key role in mitochondrial energy production, and its absence leads to progressive cardiac stress, hypertrophy and eventual heart failure.
The phase 1 study enrolled 17 adult patients with FA-associated cardiomyopathy who received a single intravenous infusion of the therapy across three dose levels. According to Crystal, the treatment was generally well tolerated and showed signs of biological activity.
“We’re using a virus to transfer the normal gene directly to the heart to cure the heart disease,” Crystal explained.
Beyond the heart, Crystal said the therapy also appeared to stabilize neurological function, as measured by the modified Friedreich’s Ataxia Rating Scale (mFARS). He said this was a added bonus, as the the study was primarily focused on cardiac outcomes.
The findings represent the first clinical demonstration of gene therapy targeting the cardiac manifestations of FA. While other research groups are pursuing similar strategies, Crystal noted that his team has been developing this approach for more than a decade, with initial research dating back to 2014.
Based on these early results, the therapy’s developer, Lexeo Therapeutics, is preparing to advance the program into a larger trial aimed at securing regulatory approval.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: [email protected]