First in Israel: Gene-Editing Therapy for Heart Failure
- RHCC
- 1 day ago
- 4 min read
For the first time in Israel, Rambam Health Care Campus (Rambam) is testing a revolutionary gene-editing treatment that could halt a deadly form of heart failure. The same technology may soon target another global killer: high cholesterol.
In collaboration with Intellia Therapeutics, a U.S. biotech company, Rambam is conducting the first gene-editing clinical trial of its kind in Israel to treat transthyretin amyloidosis. The condition is sometimes hereditary, but more often age-related, making this trial an important step toward using gene editing to treat a broader range of diseases. In parallel, other drug companies are testing similar approaches to treat high cholesterol.
“Amyloidosis refers to a group of conditions marked by the accumulation of abnormal protein deposits in organs and tissues,” explains Dr. Oren Caspi, Director of the Heart Failure Unit and Head of the Palti and Perlhagen Center for Research and Innovation in Cardiovascular Medicine at Rambam. Dr. Caspi is leading the Rambam trial together with colleagues, Dr. Sirosh Petcherski and Dr. Ronnie Abbo, both from the Department of Cardiology.
Genes serve as the blueprint for encoding proteins. If coding is disrupted, proteins may become misfolded or improperly processed, causing dysfunction, an accumulation in the tissue, and a range of inherited or age-related diseases or complications, including heart failure, cardiac arrhythmias, and even death. Approximately five percent of individuals diagnosed with heart failure have this form of amyloidosis.
“When I was a medical student, amyloidosis was considered serious—and sometimes fatal. But in recent years, more advanced treatment options have evolved,” states Dr. Caspi. “ In 2016, research revealed that amyloidosis could be diagnosed with a relatively simple test, and sparked an effort to develop effective therapies. Two years ago, one such treatment became available and, while it does not halt the disease, it slows deterioration.”
Two characteristics of amyloidosis make it a promising candidate for gene-editing therapy. First, the specific protein is not required in large quantities, so production can be safely suppressed without compromising overall health. Second, the liver—where the protein is produced—is comparatively easy to target with drug delivery.
The drug is built on Nobel Prize-winning, gene editing-technology—CRISPR-Cas9 —which precisely modifies DNA sequences and prevents the production of the disease-causing protein.
The treatment is designed to have a long-lasting effect—possibly a one-time therapy. However, since the liver cells naturally regenerate, some patients may eventually require another treatment after many months or even years. When delivered in the early stages of disease, it can prevent the progression to heart failure and presents a significant advantage for elderly patients, who frequently struggle to adhere to medication regimens.
Gene-editing to treat amyloidosis-induced heart failure is cost-effective as it has a potential to alter the disease’s trajectory. “This is personalized medicine that can change the course of the illness,” says Dr. Abbo. “One of the goals of the trial is to recruit and support more patients who could benefit from this approach.”
“The drug is delivered using an IV, but the delivery vehicle can provoke an immune response. To mitigate this, patients receive temporary immunosuppressive medication around the time of infusion,” adds Caspi. “ In preclinical trials, no adverse effects have been observed. We are confident in the product’s safety, though, safety testing is an essential part of drug development.”
High Cholesterol?
Gene-editing therapies are being used to treat hereditary diseases caused by single-gene defects, such as beta thalassemia and sickle cell anemia. However, until recently, no therapies had been developed for age-related conditions. In the case of amyloidosis, it is possible to modify the protein production mechanism with minimal risk. Drs. Caspi and Abbo add that other conditions—such as high cholesterol—could also benefit from similar approaches, and drug manufacturers are working on this.
Although cholesterol is a fatty molecule rather than a protein, researchers apply a similar therapeutic strategy: they target the genes that encode proteins regulating cholesterol levels. The treatment mimics a population-specific genetic mutation that safely lowers cholesterol production without known adverse effects.
In an early-stage trial conducted by CRISPR Therapeutics, participants with severely elevated cholesterol levels—due to underlying genetic mutations—experienced a marked reduction in “bad” cholesterol and triglyceride levels, demonstrating the promise of this approach.
Looking ahead, gene-editing therapy may prove beneficial for a broader population—including individuals with moderately elevated cholesterol levels, regardless of the cause. To date, no significant adverse effects have been reported.
Verve Therapeutics, a Boston-based biotech company, is advancing a larger clinical trial to evaluate its gene-editing therapy targeting cholesterol, using a slightly different mechanism from traditional approaches. The company has also drawn international attention with its planned acquisition by Eli Lilly, valued at over $1 billion.
While existing cholesterol-lowering medications—such as statins—are generally effective and well-tolerated, they can cause side effects. Additionally, the daily dosing regimen can be complex and burdensome, especially for long-term management.
Gene-editing therapies may offer a promising alternative for controlling cholesterol levels, but substantial research is still required. Moreover, any such therapy must undergo rigorous evaluation and receive FDA approval before it can be implemented in clinical practice.
