To date, genetically modified therapies have been mainly intended for people suffering from rare genetic diseases. Gaining traction, however, is the idea that gene editing can also be used to treat diseases that are not necessarily hereditary or rare. Only recently, a gene therapy developed by US firm Intellia Therapeutics was first trialed at Rambam Health Care Campus to treat a non-hereditary genetic disease: Transthyretin cardiac amyloidosis (ATTR-CA). A therapy for non-genetic high cholesterol is being tested in locations around the world; its mechanism is similar to that of the ATTR-CA product being tested at Rambam.
Disease no longer a death sentence
Amyloidosis is an umbrella term for diseases characterized by the accumulation of proteins in excessive quantities or in the wrong places, explains Dr. Oren Caspi, Director of the Heart Failure Unit and Head of Rambam's Cardiovascular Research and Innovation Center, who led the clinical trial with Dr. Sirouch Petcherski and Dr. Aharon (Ronnie) Abbo. Genes are the program by which proteins are encoded. When there is a defect in the coding chain - from DNA to protein - proteins may form that do not fold well and therefore end up in the wrong place, or the system that is supposed to break them down fails, creating an unnecessary accumulation of proteins.
In ATTR-CA, the proteins do not fold well because of a genetic defect or, more commonly, due to old age. The accumulation of proteins causes heart failure, cardiac arrhythmias, and even death. It is estimated that about 5% of those diagnosed with heart failure have this type of amyloidosis.
"When I studied medicine, this disease was considered serious and even terminal," Caspi says. However, in recent years, there have been extremely rapid developments in its treatment. "In 2016, an article was published for the first time showing that the disease can be identified with a relatively simple test. The race to develop a drug began immediately, and there has been one on the market for over two years. But the existing drug doesn't stop the deterioration, it only slows it down."
An easier solution for patients
Two features of the disease make it well-suited to treatment with genetic editing. First, the body can function without large amounts of the protein, meaning its production can safely be halted. Second, the protein is produced in the liver, an organ that readily absorbs genetically edited therapies.
The drug, based on Nobel Prize-winning gene-editing technology CRISPR-Cas9, reaches the liver cells and splices out the defective gene so that it cannot manufacture the protein that causes the disease. Once treated, the change to the liver cells is irreversible.
This gene therapy is designed to halt the progression of the disease. It offers long-term benefit - potentially as a one-time treatment, though in some cases periodic maintenance may be needed over months or years as liver cells regenerate. When administered early, it can even prevent heart failure from developing. For older patients, the hospital notes, the prospect of infrequent treatment is especially valuable, as managing complex drug regimens can be particularly challenging for them
The existence of such a treatment increases the incentive to detect those whose heart failure is due to amyloidosis, even before the condition worsens, in a way that will save high costs of treatment. "This is really personalized medicine, which can bring about a complete change in the course of the disease, and we are interested in helping additional patients as part of the research that continues to take place at Rambam," says Dr. Abbo.
What does the treatment look like?
Caspi: "The patient receives the drug intravenously. Before that, they receive immunosuppressive therapy, because we know that the body can have an immune response, not to the drug itself, but to the envelope in which the drug is delivered. Immunosuppression is only for the course of treatment."
And we know there’s no other changes aside from the gene you intended to edit?
"In pre-clinical trials, that is, in animals, it has been demonstrated many times that there are no such changes. We strongly believe in the safety levels of the product, but of course this is also part of what is tested in the trial."
A promising cholesterol trial
Genetically modified drugs are already being used today to treat hereditary diseases resulting from a defect in a single gene, such as beta thalassemia or sickle cell anemia. Until now, there have been no such drugs to treat the disease, which develops with age. The advantage in the case of amyloidosis is that the mechanism that produces protein in the body can be halted almost without any damage. There are other diseases with this potential, Caspi and Abbo say. One of the most interesting of them is hypercholesterolemia or high cholesterol.
Intellia, the company for which Caspi and his group conducted the current experiment, is one of the companies operating in this field, along with companies such as CRISPR Therapeutics, Beam Therapeutics, and Verve, which is expected to be acquired soon by Eli Lilly for $1-1.3 billion.
Although cholesterol itself is a fatty substance rather than a protein, the therapeutic goal is to target the genes that encode the proteins responsible for regulating cholesterol levels in the body. The treatment is designed to replicate a naturally occurring genetic mutation found in a subset of the population, which results in lower cholesterol production-without causing them any harmful health effects
In an initial trial by CRISPR Therapeutics, the results of which were published last May, there was a substantial reduction in the patients' levels of "bad" cholesterol and triglycerides. The trial subjects had particularly high cholesterol levels, due to genetic mutation, or else they simply had abnormally high cholesterol levels. In the future, the treatment may also be relevant to a wider population, those with moderate cholesterol levels regardless of origin -- usually a combination of hereditary and environmental factors. So far, no problematic side effects have been observed for the treatment.
Verve is expected to present results in the coming months from a larger trial, using a slightly different mechanism, of a gene-edited anti-cholesterol drug.
Existing cholesterol medications, such as statins, are effective and safe in most of the population, but cause side effects in some patients, and the regimen can be complex and burdensome. Long-term treatment may be an advantageous alternative.
The politics of approvals
In the meantime, any gene therapy will have to go through the US Food and Drug Administration’s Center for Biologics Evaluation and Research. Recently, Dr. Vinayak "Vinay" Prasad was appointed head of this division. He is considered tough in terms of the requirements he sets for pharmaceutical companies. Two weeks ago, Prasad was fired from his position, due to doubts about the extent of his support for US President Donald Trump and following the halt in marketing Sarepta’s gene therapy for Duchenne muscular dystrophy. At the end of last week, it was decided to reinstate him. If Prasad does remain in his position for a long time, his tough approach may affect the speed at which these treatments will reach the market, but it will mean we can assume that they were tested rigorously and thoroughly.
Published by Globes, Israel business news - en.globes.co.il - on August 21, 2025.
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