Tag: Medicine

For the first time, researchers uncover the biological mechanism that enables breast cancer to spread to the brain, opening new paths for treatment and early detection

A large-scale international study, led by researchers from the Gray Faculty of Medical and Health Sciences at Tel Aviv University, has uncovered a mechanism that allows breast cancer to send metastases to the brain — a highly lethal occurrence for which there is currently no effective treatment. The findings could enable the development of new drugs and personalized monitoring for early detection and treatment of brain metastases.

The groundbreaking study was led by Prof. Uri Ben-David and Prof. Ronit Satchi-Fainaro, along with researchers Dr. Kathrin Laue and Dr. Sabina Pozzi from their laboratories at the Gray Faculty of Medical and Health Sciences at Tel Aviv University, in collaboration with dozens of researchers from 14 laboratories in 6 countries (Israel, the United States, Italy, Germany, Poland, and Australia). The article was published in the journal Nature Genetics.

Why Do Some Cancers Spread to the Brain?

Prof. Satchi-Fainaro explains: “Most cancer-related deaths are not caused by the primary tumor but by its metastases to vital organs. Among these, brain metastases are some of the deadliest and most difficult to treat. One of the key unresolved questions in cancer research is why certain tumors metastasize to specific organs and not others. Despite the importance of this phenomenon, very little is known about the factors and mechanisms that enable it. In this study, we joined forces to deepen our understanding and seek answers.”

Left to right: Prof. Satchi-Fainaro & Prof. Uri Ben-David.

Combining Genetics and the Tumor Microenvironment

The current study combined two distinct approaches to cancer research: Prof. Satchi-Fainaro’s lab, which studies the interactions between cancer cells and their surrounding environment (the tumor microenvironment), and Prof. Ben-David’s lab, which investigates chromosomal changes that characterize cancer cells. The complex study involved numerous scientific methods and technologies, including clinical and genomic data analysis of tumors from breast cancer patients, genetic, biochemical, metabolic, and pharmacological experiments in cultured cancer cells, and functional experiments in mice.

The researchers first identified a specific chromosomal alteration in breast cancer cells that predicts a high likelihood of brain metastases. Prof. Ben-David explains: “We found that when chromosome 17 in a cancer cell loses a copy of its short arm, the chances of the cell sending metastases to the brain greatly increase. We also discovered that the reason for this is the loss of an important gene located on this arm. This gene is p53, often referred to as ‘the guardian of the genome,’ and it plays a crucial role in regulating cell growth and division. We discovered that the absence of a functional p53 is essential for the formation and proliferation of cancerous brain metastases. When we injected mice brains with cancer cells with or without functional p53, we found that cells with disrupted p53 activity thrived much more. We sought to understand the mechanism causing this.”

How Cancer Cells Adapt to the Brain Environment

Prof. Satchi-Fainaro adds: “The brain’s environment is fundamentally different from that of the breast, where the primary tumor develops, and the question is how a breast cancer cell, adapted to its original environment, can adjust to this foreign one. According to our findings, this adaptation is closely linked to the impairment of the p53 gene. We found that p53 regulates the synthesis of fatty acids, a metabolic process particularly vital in the brain environment. This means that cells with damaged p53, or without p53 at all, produce more fatty acids compared to normal cells, which in turn enables them to grow and divide more rapidly in the brain.”

Left to right: Dr. Kathrin Laue & Dr. Sabina Pozzi.

Hijacking Brain Cells to Fuel Tumor Growth

The next phase of the study focused on the components of the brain environment and the communication between brain cells and cancer cells. The researchers identified heightened interaction between cancer cells with damaged p53 and astrocytes — support cells in the brain that secrete substances aiding neurons. In the absence of p53, the cancer cells hijack the substances secreted by the astrocytes and use them to produce fatty acids. The researchers identified a specific enzyme named SCD1 — a key enzyme in fatty acid synthesis — whose expression and activity levels are significantly higher in cancer cells with impaired or missing p53.

Prof. Ben-David: “Once we identified the mechanism and its key players, we sought to use the findings to search for a potential drug for brain metastases. We chose to focus on the SCD1 enzyme and tested the effectiveness of several drugs that inhibit its activity and are currently under development. These drugs were originally indicated for other diseases, but we found that SCD1 inhibition in brain metastatic cells with impaired p53 was effective and significantly hindered the development and proliferation of cancerous metastases — both in mice and in samples from brain metastases of women with breast cancer.”

The researchers add that their findings may also assist doctors and patients in predicting disease progression: even at an early stage of breast cancer, it is possible to identify whether there is a p53 mutation (or deletion of the short arm of chromosome 17), which significantly increases the risk of brain metastases later on. For example, doctors could avoid prescribing aggressive biological treatments with severe side effects for patients not at high risk of brain metastases, while opting for aggressive treatment when the risk is elevated. In addition, physicians can tailor monitoring to the patient’s risk level — such as frequent brain MRI scans for patients at increased risk of brain metastases. This type of intensive monitoring would allow for early detection and treatment, significantly increasing the chances of recovery.

Looking Ahead

The researchers conclude: “In this study, we joined forces in an extensive international effort to address a highly important question: What is the mechanism that enables breast cancer to metastasize to the brain? We identified several characteristics of cancer cells causally linked to this deadly phenomenon, and the findings allowed us to propose new drug targets for brain metastases — a condition for which no effective treatment currently exists. Moreover, we tested drugs that inhibit a specific metabolic mechanism, SCD1 inhibitors, and found them to be effective against brain metastases. Additionally, our findings are expected to enhance oncologists’ ability to identify patients at elevated risk and prepare accordingly. While the road ahead is still long, the potential is immense.”

The project was supported by competitive research grants from the Israel Science Foundation (ISF), the Israel Cancer Research Fund (ICRF), and the Spanish bank Fundacion “La Caixa.” It is also part of broader research being conducted in Prof. Satchi-Fainaro’s lab, supported by an Advanced Grant from the European Research Council (ERC), ERC Proof of Concept (PoC), and the Kahn Foundation, as well as broader research being conducted in Prof. Ben-David’s lab, supported by an ERC Starting Grant.

TAU-led study uncovers how cancer cells disable the immune system

A new international study led by the Gray Faculty of Medical & Health Sciences at Tel Aviv University finds: melanoma cancer cells paralyze immune cells by secreting extracellular vesicles (EVs),

which are tiny, bubble-shaped containers secreted from a given cell. The research team believes that this discovery has far-reaching implications for possible treatments for the deadliest form of skin cancer.

How Melanoma Silences Immune Cells

This dramatic breakthrough led by Prof. Carmit Levy of the Department of Human Genetics and Biochemistry at TAU’s Gray Faculty of Medical & Health Sciences, in collaboration with research teams from Sheba Medical Center, the Weizmann Institute of Science, the University of Liège, the Technion, Tel Aviv Sourasky Medical Center, Wolfson Medical Center, Massachusetts General Hospital, Hadassah Medical Center, the Hebrew University of Jerusalem, Rabin Medical Center, Paris-Saclay University, and the University of Zurich. The study’s findings were published in the prestigious journal Cell.

Melanoma cells (green) are shown in co-culture with the patient’s own immune cells from Sheba Medical Center.

A New Role for Cancer-Secreted Vesicles

Melanoma is the deadliest type of skin tumor. In the first stage of the disease, melanocytic cells divide uncontrollably in the skin’s outer layer, the epidermis. In the second stage, the cancer cells invade the inner dermis layer and metastasize through the lymphatic and blood systems. In previous studies, Prof. Levy discovered that as they grow in the epidermis, melanoma cells secrete large extracellular vesicles (EVs) called melanosomes, which penetrate blood vessels and dermal cells, forming a favorable niche for the cancer cells to spread. The new study found that these vesicles also enable cancer cells to paralyze the immune cells that attack them.

“We began studying these vesicles,” says Prof. Levy, “and I noticed that on the vesicles membrane there was a ligand — a molecule that is supposed to bind to a receptor found only on immune cells called lymphocytes, specifically on lymphocytes that can kill cancer cells when coming into direct contact with them. I than hypothesis that this ligand latches onto lymphocytes that come to kill the melanoma. This was an innovative and odd idea and we start investigating it in the lab. When we got more and more evidence that this idea is correct, I spoke with colleagues around the world, and invited them to joined and contribute their expertise: from Harvard, from Sheba and from Ichilov’s pathology department, from the Weizmann Institute, from Zurich, Belgium and from Paris — all came together in a joint effort to decipher the cancer’s behavior. And the achievement is enormous: we discovered that the cancer essentially fires these vesicles at the immune cells that attack it, disrupting their activity and even killing them.”

Toward New Immunotherapy Strategies

Prof. Levy emphasizes that the remarkable discovery is promising however more work is require further in order to translate it into a new therapy. “We still have a great deal of work ahead of us, but it is already clear that this discovery can have far-reaching therapeutic implications,” says Prof. Levy. “It will enable us to strengthen immune cells so they can withstand the melanoma’s counterattack. In parallel we can block the molecules that enables vesicles to cling to immune cells, thereby exposing the cancer cells and making them more vulnerable. Either way, this study opens a new door to effective immunotherapeutic intervention.”

TAU meta-analysis finds pathogens, storms, and extreme temperatures are the leading causes of sea urchin mass mortality events.

Two pioneering studies by researchers from the School of Zoology and the Steinhardt Museum of Natural History at Tel Aviv University, led by Dr. Omri Bronstein, have identified the primary drivers of sea urchin mass mortality events over recent decades: pathogens, storms, and extreme temperatures. In addition, Dr. Bronstein and his team have developed an innovative method for genetic sampling in marine environments – using a swab similar to a COVID-19 test — to enable rapid and non-invasive monitoring of marine animals and underwater disease outbreaks.

The first study, published in the journal Biological Reviews, presents a meta-analysis of all 110 scientifically documented mass mortality events (MMEs) among sea urchins recorded between 1888 and 2024. Dr. Bronstein and PhD student Lisa Schmidt conducted a comprehensive review of the history of these events, showing that most reported MMEs originate in the Northern Hemisphere — particularly in the United States, Western Europe, and Japan — where the majority of research and funding are concentrated. The Tel Aviv University researchers classified five main causes of these events and found that 33% were caused by pathogens, 25% by catastrophic events such as storms and oxygen depletion, 24% by extreme temperatures, 11% by algal blooms, and 7% by human activity, such as pollution and habitat destruction.

Left to right: Mai Bonomo & Dr. Omri Bronstein holding sea urchin and sample tube

“This is a meta-analysis of all scientific literature on the subject,” says Dr. Bronstein. “For each mass mortality event, we mapped where and when it occurred, which species were affected, and most importantly — what the causes were. After filtering out hundreds of publications who lacked sufficient credible data to be included in our analyses, ee found that pathogens are the leading cause of mass mortalities among sea urchins. This finding aligns closely with what we are seeing today in the modern wave of die-offs — from the Caribbean to the Red Sea and the Indian Ocean. There is a tendency to attribute everything to global warming, but that is not always accurate. In many cases, mortality is not directly related to heat, as some affected sea urchin species naturally live in even warmer environments. These temperatures may not be optimal, but they are not lethal for these species. The problem is that warming influences many other environmental factors, which can combine into a deadly mix. For example, warmer waters tend to have lower dissolved oxygen and higher pathogen activity.”

A Global Sea Urchin Pandemic

In 2023, Dr. Bronstein identified a mass mortality event of long-spined sea urchins (Diadema setosum) along the Red Sea coast. He subsequently found that the same pathogen — a ciliate parasite — responsible for wiping out a related Caribbean species was also to blame. Since that discovery, the outbreak has spread to the Indian Ocean, reappeared in the Caribbean, and is now considered a global pandemic threatening sea urchin populations worldwide.

“Sea urchins are vital to coral reef health,” explains Dr. Bronstein. “They are the ‘gardeners’ of the reef: they feed on algae and prevent it from overgrowing and suffocating the corals competing for sunlight. In 1983, the most dominant Caribbean sea urchin species, Diadema antillarum, died in vast numbers from an unknown reason at the time; algae proliferated uncontrollably, shaded the corals, and the entire ecosystem shifted from coral reefs to algal fields. Even 40 years later, the sea urchin population — and the reefs — have not recovered. We fear that the same process may now occur in other parts of the world where mass die-offs are happening, mainly among the long-spined sea urchin, a relative of the Caribbean species — the black urchin with long spines familiar to everyone. Until recently, it was one of the most common reef urchins in Eilat; today it has almost disappeared from large parts of the Red Sea. This is a very violent event: within less than 48 hours, a healthy population turns into disintegrating skeletons. In some sites in Eilat and Sinai, mortality reached 100%. Later, mass deaths were recorded on Réunion Island in the Indian Ocean, and we are now investigating three additional mass mortality events in the Atlantic and Indian Ocean, and even the Mediterranean Seas. What began as a local mortality event has become regional and then global, posing a threat to coral reefs everywhere.”

Close-up of hand swabbing sea urchin underwater tank

The Challenge of Genetic Sampling Underwater

To address one of the major challenges in marine genetic sampling, graduate student Mai Bonomo and Dr. Bronstein published a separate study in Molecular Ecology Resources, developing a new, inexpensive, and non-invasive method for collecting underwater genetic samples at scale.

“The main tools used today to identify both animals and pathogens are genetic,” says Dr. Bronstein. “But molecular ecology faces a fundamental problem: there’s no simple way to sample DNA from live marine animals underwater. As a result, many studies rely on invasive methods that harm the animal or even require sacrificing it completely to bring it into the lab. Therefore, research in this field is heavily regulated, weighing each case’s scientific value against environmental ethics. For example, sampling is prohibited in marine nature reserves, there are restrictions and bans on shipping samples abroad — including corals — and every scientific publication must present the official permits for each sample it reports. Our need to overcome this bottleneck arose from the sea urchin pandemic. Today, there are only two ways to detect diseased urchins: visually — which is too late, as the animals are already dying — or through genetic tools that can detect disease before symptoms appear. But if detecting disease requires removing the animal from the sea, it makes no difference whether it’s sick or not — we end up sacrificing it.”

A Simple New Tool for Rapid, Non-Invasive Sampling

To overcome this challenge, Tel Aviv University researchers developed a specialized underwater genetic sampling kit that is durable, reliable, inexpensive, and easy to use — and it is already being adopted by research groups worldwide, especially in remote or sensitive areas.

“We developed a new tool for underwater DNA sampling that resembles a COVID-19 test,” explains Dr. Bronstein. “At the end of a special tube filled with a preservation liquid is a membrane preventing water penetration, sealed with a clip-cap — much like some toothpaste tubes. Just like a COVID test, the researcher gently swabs the surface of the marine animal, without harming or moving it. There’s no need to collect mucus as in humans — just a light swipe is enough. The swab is then inserted into the tube, piercing the membrane that protects the preservation liquid inside, and the cap is locked to secure the sample. That’s it. A single researcher can collect dozens of samples in one dive, under almost any environmental or depth conditions.

The kit has already been tested in challenging environments, including field expeditions to Djibouti and Réunion Island, and the results are very promising: samples remained exceptionally well-preserved for months without refrigeration before arriving at our lab, and still allowed for sensitive genetic analyses. In a large-scale trial we conducted in the Gulf of Eilat, we collected genetic material from hundreds of echinoderms — the group that includes sea urchins and starfish — within just a few months, and performed the most extensive genetic analysis ever conducted on these species in the region. This led to the discovery of several new species and the reclassification of others previously unknown to science. This is a simple and elegant solution to one of the most persistent technical challenges in marine molecular ecology.”

TAU researchers discover how to increase myelin production — a finding that could aid treatments for Alzheimer’s and multiple sclerosis.

Researchers from Tel Aviv University have discovered a new biological mechanism that enhances the production of myelin — a substance essential for proper brain function and nerve communication. “Our findings may serve as the basis for developing innovative treatments for severe neurological disorders involving myelin damage, including multiple sclerosis, Alzheimer’s disease, and certain neurodevelopmental syndromes,” the researchers note.

The study was conducted in the laboratory of Prof. Boaz Barak of the Sagol School of Neuroscience and the School of Psychological Sciences at Tel Aviv University and led by Dr. Gilad Levy. The lab collaborated with researchers from the Hebrew University of Jerusalem, the Weizmann Institute of Science, Tel Aviv University, and Germany’s Max Planck Institute. The findings were published in Nature Communications.

Releasing the Brain’s “Biological Brakes”

Prof. Barak explains: “Damage to myelin is associated with a variety of neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis (an autoimmune disease in which the body itself attacks the myelin), as well as neurodevelopmental syndromes like Williams syndrome and autism spectrum disorders. In this study we focused on the cells that produce myelin in both the central and peripheral nervous systems. Specifically in these cells, we investigated the role of a protein called Tfii-i, known for its ability to increase or decrease the expression of many genes crucial for cell function. While Tfii-i has long been linked to abnormal brain development and neurodevelopmental syndromes, its role in myelin production had not been studied until now.”

Prof. Barak’s team discovered that the Tfii-i acts as a ‘biological brake’ that inhibits myelin production in the relevant cells. Based on this finding, the researchers hypothesized that reducing Tfii-i activity in myelinating cells might increase myelin output.

Prof. Boaz Barak

Testing the Hypothesis

To test this, the team  used advanced genetic engineering in model mice: Tfii-i expression was selectively eliminated only in myelin-producing cells, while remaining unchanged in all other cells. These genetically modified mice were compared to normal mice in a wide variety of measures, including levels of myelin proteins, structure and thickness of the myelin sheath surrounding axons, speed of nerve signal conduction, and even motor and behavioral performance.

Dr. Gilad Levy explains: “We found that in the absence of Tfii-i, the myelin-producing cells generated higher amounts of myelin proteins. This resulted in abnormally thick myelin sheaths, which enhanced the conduction speed of electrical signals along the neural axons. These improvements resulted in a significant enhancement of the mice’s motor abilities, including better coordination and mobility, along with other behavioral benefits.”

Prof. Barak concludes: “In this study we demonstrated for the first time that it is possible to ‘release the brakes’ on myelin production in the brain and peripheral nervous system by regulating the expression of Tfii-i. This study is among the few to identify a mechanism for increasing myelin levels in the brain. Its results may enable the development of future therapies that suppress Tfii-i activity in myelin-producing cells, to restore myelin in a wide variety of degenerative and developmental diseases in which myelin is impaired — including Alzheimer’s disease, multiple sclerosis, Williams syndrome, and autism spectrum disorders. We believe this fundamentally new approach holds great therapeutic potential.”

A new study from Tel Aviv University and Dana Dwek Children’s Hospital shows that obese children can remain healthy if liver fat is kept low — highlighting diet quality as a key factor in preventing disease.

A study conducted at Tel Aviv University and Dana Dwek Children’s Hospital in Tel Aviv found that disease can be prevented in children with obesity by maintaining a low percentage of fat in the liver. The researchers used innovative methods to examine 31 Israeli children with obesity, in an attempt to understand why some have developed illnesses as a result of their excess weight — while others remain healthy (so far). They discovered that the percentage of fat in the livers of children already experiencing illness was two and a half times higher – 14% compared to 6% – than in the group of healthy obese children.

Quality Over QuantityThe researchers emphasize that, according to the findings, the health of obese children is influenced not only by the quantity, but also by the quality and composition of the food they eat. “The study indicates that even if obese children do not lose weight or reduce their food intake, their health can be protected by monitoring the components of their diet and minimizing fatty liver damage,”they explain.

Study Design and Methods

The groundbreaking study was led by Prof. Yftach Gepner and doctoral student Ron Sternfeld from the Gray Faculty of Medical and Health Sciences and the Sylvan Adams Sports Science Institute at Tel Aviv University, together with Prof. Hadar Moran-Lev and Prof. Ronit Lubetzky from the Dana Dwek Children’s Hospital. The findings were published in the journal Frontiers in Nutrition.

Ron Sternfeld explains: “This is a cross-sectional study, which means we did not follow the children over time but rather examined them thoroughly at one point in time. Therefore, we can only indicate correlation, but not causality in our findings. Nonetheless, the study is important and unique, investigating why some obese children remain metabolically healthy, while others of the same weight already show signs of metabolic disease. To this end, we conducted a wide range of medical tests and reviewed the children’s medical records dating back to the prenatal stage. The highlight of the study was the use of MRS technology — an advanced non-invasive method that directly assesses liver composition, enabling precise measurement of liver fat percentage during MRI scans. This is one of the few studies ever to use MRS for diagnosing fatty liver in obese children.

Key Findings

To identify the best predictor of metabolic disease in obese children, the researchers examined 31 children treated at the Obesity Clinic of Dana Dwek’s Gastroenterology Institute. The children were similar in age and body weight, but one group was still metabolically healthy while the other already showed abnormal rates of fasting glucose, blood lipids, cholesterol, and/or blood pressure. The researchers found that the factor most associated with metabolic illness was the percentage of fat in the liver: 14% in children already showing illness, compared to only 6% in the group of obese but still healthy children.

“We checked many different criteria and found no difference between the two groups,” says Ron Sternfeld. “For example, we found no difference in the visceral fat which surrounds internal organs in the abdomen, considered a major metabolic risk indicator. In contrast, a dramatic gap was found in the percentage of fat in the liver. Fatty liver is defined as a condition where more than 5.5% of the liver is composed of fat. Linked to diabetes, high blood pressure, sleep apnea, and more, fatty liver is considered one of the main causes of illness associated with obesity. To our surprise we found that some obese children do not have fatty liver.”

Looking Ahead

According to the researchers, this phenomenon is difficult to explain — although some hypotheses can be suggested. Prof. Gepner: “Comparing the children’s diets, we found that those already ill consume higher levels of sodium, processed food, and certain saturated fatty acids from animal protein — mainly red meat. This means that the quality, not just the quantity of the food, plays a role. A Mediterranean diet may provide protection against metabolic illness, even in the case of obesity. Another possibility has to do with the children’s medical history: we found that three times as many children in the ‘unhealthy obesity’ group, compared to those still healthy, had been born following high-risk pregnancies. Whatever the precise cause, our study strengthens the hypothesis that the liver is the most important metabolic organ and should be a primary target for preventive medicine.”

TAU researchers have developed a targeted method of delivering locked nucleic acids (LNAs) using lipid nanoparticles, achieving therapeutic effect against inflammatory bowel disease in preclinical models — without side effects.

Researchers at Tel Aviv University have developed a new approach for using locked nucleic acids (LNAs) – a particularly stable type of RNA – to treat inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis. The researchers encapsulated selected LNA molecules, which silence a key gene in colitis, within lipid (fat) nanoparticles that serve as targeted drug carriers and injected the nanoparticles into colitis-model mice. The findings indicated improvement in all markers of systemic inflammation, with no side effects. According to the researchers, this innovative method may also be suitable for a wide range of other diseases – including rare genetic disorders, vascular and heart diseases, and neurological diseases such as Parkinson’s and Huntington’s.

The study was conducted by the group of Prof. Dan Peer, a pioneer in the use of RNA molecules for therapy and vaccines, world expert in nanomedicine, and a senior faculty member at TAU’s Shmunis School of Biomedicine and Cancer Research, Department of Materials Sciences and Engineering at the Fleischman Faculty of Engineering, Jan Koum Center for Nanoscience and Nanotechnology, and Cancer Biology Research Center. The group, led by Neubauer doctoral student Shahd Qassem together with Dr. Gonna Somu Naidu, a postdoctoral fellow who collaborated with researchers from F. Hoffman La-Roche (Roche) pharmaceutical company in Switzerland. The article was published in Nature Communications.

Overcoming Previous Limitations of LNA

Prof. Peer explains: “Our study focused on unique RNA molecules called LNA. Unlike most RNA molecules, LNA molecules are very stable and do not break down easily. Consequently, until about 10 years ago, they were thought to have great potential as genetic drugs. However, experiments in laboratory animals, as well as clinical trials in humans (in chronic liver inflammation), showed that very large amounts of LNA are needed to achieve therapeutic efficacy. Moreover, administered by injection as a free drug, this high dosage proved very costly and caused severe side effects when spreading throughout the body. As a result, the effort to develop LNA-based drugs was abandoned. In our study we sought to test a new, better targeted and more effective approach.”

Prof. Dan Peer

Targeted Delivery With Lipid Nanoparticles

The researchers used a method previously developed at Prof. Peer’s lab for other RNA molecules (such as siRNA, mRNA, circRNA), now applying it to LNA: they encapsulated the molecules in lipid nanoparticles (LNPs) that serve as targeted drug carriers, delivering their therapeutic payload directly to the relevant organ in the body. Specifically, they chose an LNA molecule known to silence the TNFα gene, which plays a significant role in inflammatory bowel diseases. Screening a lipid library developed in Prof. Peer’s lab over the past 13 years, they identified the most suitable lipid molecules and encapsulated the LNA molecules in them. The resulted LNPs were injected into mice in a model of chronic bowel diseases such as colitis.

The findings were highly encouraging: the dosage required to achieve the desired therapeutic effect was 30 times lower compared to past studies – in which LNA molecules were administered as a free drug without lipid encapsulation. At the current dosage, delivered precisely to the correct site, the drug proved highly effective in treating the disease, without causing any side effects.

Prof. Peer: “Our study paves the way to developing new LNA-based drugs for inflammatory bowel diseases, as well as a wide range of other diseases – including rare genetic disorders, vascular and heart diseases, and neurological diseases such as Parkinson’s and Huntington’s. So far, we have demonstrated that the new method is effective in chronic bowel inflammation in mice. We hope to proceed to clinical trials in humans in the near future.”

TAU researchers created a gene therapy that protects against hearing and balance impairments caused by inner ear dysfunction.

Scientists from the Gray Faculty of Medical & Health Sciences at Tel Aviv University introduced an innovative gene therapy method to treat impairments in hearing and balance caused by inner ear dysfunction. According to the researchers, “This treatment constitutes an improvement over existing strategies, demonstrating enhanced efficiency and holds promise for treating a wide range of mutations that cause hearing loss.”

The study was led by Prof. Karen Avraham, Dean of the Gray Faculty of Medical & Health Sciences, and Roni Hahn, a PhD student from the Department of Human Molecular Genetics and Biochemistry. The study was conducted in collaboration with Prof. Jeffrey Holt and Dr. Gwenaëlle Géléoc from Boston Children’s Hospital and Harvard Medical School and was supported by the US-Israel Binational Science Foundation (BSF), the National Institutes of Health/NIDCD and the Israel Science Foundation Breakthrough Research Program. The study was featured on the cover of the journal EMBO Molecular Medicine.

Prof. Avraham explains: “The inner ear consists of two highly coordinated systems: the auditory system, which detects, processes, and transmits sound signals to the brain, and the vestibular system, which enables spatial orientation and balance. A wide range of genetic variants in DNA can affect the function of these systems, leading to sensorineural hearing loss and balance problems. Indeed, hearing loss is the most common sensory impairment worldwide, with over half of congenital cases caused by genetic factors. In this study, we aimed to investigate an effective gene therapy for these cases using an approach that has not been applied in this context before.”

Targeting the CLIC5 Gene

Roni Hahn: “Gene therapy has emerged as a powerful therapeutic approach in recent years and is now being applied to a range of genetic disorders, including spinal muscular atrophy (SMA) and Leber congenital amaurosis (LCA), as well as in cancer immunotherapy approaches such as CAR T-cell therapy. One of the treatment strategies includes the use of engineered viral vectors, in which the native DNA is replaced with a functional sequence of the target gene. These vectors utilize the virus’s natural ability to enter cells to deliver the correct gene sequence, thereby restoring normal function. Many gene therapies utilize adeno-associated viruses (AAVs) to introduce therapeutic genetic material into target cells, and AAV-based gene therapy for hearing loss is currently in clinical trials, showing promising early results.

In this study, the researchers investigated a mutation in the CLIC5 gene, which is essential for maintaining the stability and function of hair cells in the auditory and vestibular systems. Deficiency of this gene causes progressive degeneration of hair cells, initially leading to hearing loss and later resulting in balance problems.

A New Generation of Viral Vectors

 The researchers utilized an advanced, structurally optimized version of the AAV vector, the self-complementary AAV (scAAV). They found that this vector achieved faster and more efficient transduction of hair cells compared to traditional AAV methods, requiring a lower dose to achieve a similar therapeutic effect. In treated animal models, this approach prevented hair cell degeneration and preserved normal hearing and balance.

Implications for Future Therapies

In summary, Prof. Avraham states: “In this study, we applied an innovative treatment approach for genetic hearing loss and found that it improves therapeutic effectiveness while also addressing combined impairments in hearing and balance. We anticipate that these findings will pave the way for developing gene therapies to treat a wide range of genetically caused hearing disorders.”

TAU researchers begin to prepare for the world’s first spinal cord implant in humans — a new development that brings fresh hope to paralyzed patients.

What if we could restore the ability to walk to people paralyzed by injury or illness?
This vision is now moving closer to reality. Three years ago, Tel Aviv University researchers succeeded in engineering a human spinal cord in the lab for the first time. Since then, progress has been rapid, with animal trials showing unprecedented success. Now, for the first time, the technology is set to be tested in human patients.

Prof. Tal Dvir, of TAU’s Sagol Center for Regenerative Biotechnology, head of the Nanotechnology Center, and Chief Scientist of the biotech company Matricelf, explains:
“The spinal cord is made up of nerve cells that transmit electrical signals from the brain to every part of the body. When the spinal cord is torn due to trauma — from a car accident, a fall, or a battlefield injury — this chain is broken. Think of it like an electrical cable that’s been cut: if the two parts don’t touch, the electrical signal can’t pass. The cable won’t carry electricity, and in the same way, the person can’t transmit the signal beyond the site of the injury.”

This is one of the few injuries in the human body with no natural ability to regenerate. “Neurons are cells that do not divide and do not renew themselves. They are not like skin cells, which can repair themselves after injury. They are more similar to heart cells: once damage occurs, the body cannot restore them,” notes Prof. Dvir.

 Engineering a Personalized Implant

To overcome this challenge, the TAU researchers developed a fully personalized process. Blood cells are taken from the patient and reprogrammed through genetic engineering to behave like embryonic stem cells, capable of becoming any type of cell in the body.

Meanwhile, fat tissue from the same patient is used to extract substances such as collagen and sugars. These are used to produce a unique hydrogel. “The beauty of this gel is that it’s also personalized, just like the cells. We take the cells that we’ve reprogrammed into embryonic-like stem cells, place them inside the gel, and mimic the embryonic development of the spinal cord,” says Prof. Dvir.

The result is a complete three-dimensional implant. “At the end of the process, we don’t just turn the cells into motor neurons — because cells alone won’t help us — but into three-dimensional tissue: neuronal networks of the spinal cord. After about a month, we obtain a 3D implant with many neurons that transmit electrical signals. These 3D tissues are then implanted into the damaged area.”

Visualization of the next stage of the research – human spinal cord implants for treating paralysis (Photo: Sagol Center for Regenerative Biotechnology)

From Animals to Human Patients

The researchers first tested the implant in lab animals. “We showed that we can treat animals with chronic injuries. Not animals that were injured just recently, but those we allowed enough time to pass — like a person more than a year after an injury. More than 80% of the animals regained full walking ability,” Prof. Dvir explains.

Encouraged by these results, the team submitted the findings to Israel’s Ministry of Health. “About six months ago we received preliminary approval to begin compassionate-use trials with eight patients. We decided, of course, that the first patient would be Israeli. This is undoubtedly a matter of national pride. The technology was developed here in Israel, at Tel Aviv University and at Matricelf, and from the very beginning it was clear to us that the first-ever surgery would be performed in Israel, with an Israeli patient.” he says.

Looking Ahead

The first implant in a human patient is expected within about a year. For the initial trials, the team will focus on patients whose paralysis is relatively recent — within about a year of injury. “Once we prove that the treatment works — everything is open, and we’ll be able to treat any injury,” says Prof. Dvir.

Behind the initiative are key figures from both academia and industry. Prof. Dvir founded Matricelf in 2019 together with Dr. Alon Sinai, based on the revolutionary organ engineering technology developed at TAU under a licensing agreement through Ramot, the University’s technology transfer company. The company’s CEO is Gil Hakim, while the scientific development is led by Dr. Tamar Harel-Adar and her team.

“They managed to get us to the stage of regulatory approvals so quickly — and that’s amazing,” says Prof. Dvir.

Gil Hakim, CEO of Matricelf , concludes: “This milestone marks the shift from pioneering research to patient treatment. For the first time, we are translating years of successful preclinical work into a procedure for people living with paralysis. Our approach, using each patient’s own cells to engineer a new spinal cord, eliminates key safety risks and positions Matricelf at the forefront of regenerative medicine. If successful, this therapy has the potential to define a new standard of care in spinal cord repair, addressing a multi-billion-dollar market with no effective solutions today. This first procedure is more than a scientific breakthrough, it is a value-inflection point for Matricelf and a step toward transforming an area of medicine long considered untreatable. We are proud that Israel is leading this global effort and are fully committed to bringing this innovation to patients worldwide.”

A TAU-led international study reveals the world’s oldest human fossil showing traits of both Neanderthals and Homo sapiens — a five-year-old child who lived 140,000 years ago in Mount Carmel’s Skhul Cave.

An international study led by researchers from Tel Aviv University and the French National Centre for Scientific Research provides the first scientific evidence that Neanderthals and Homo sapiens had biological and social relations, and even interbred for the first time, in the Land of Israel. The research team  identified combination of Neanderthal and Homo sapiens traits in the skeleton of a five-year-old child discovered about 90 years ago in the Skhul Cave on Mount Carmel. The fossil, estimated to be about 140,000 years old, is the earliest human fossil in the world to display features of both groups, which until recently were considered two separate species.

A Window into Human Evolution

The study was led by Prof. Israel Hershkovitz of the Gray Faculty of Medical and Health Sciences at Tel Aviv University and Anne Dambricourt-Malassé of the French National Centre for Scientific Research. The findings of this historic discovery were published in the journal l’Anthropologie.

“Genetic studies over the past decade have shown that these two groups exchanged genes,” explains Prof. Hershkovitz. “Even today, 40,000 years after the last Neanderthals disappeared, part of our genome—2 to 6 percent—is of Neanderthal origin. But these gene exchanges took place much later, between 60,000 to 40,000 years ago. Here, we are dealing with a human fossil that is 140,000 years old. In our study, we show that the child’s skull, which in its overall shape resembles that of Homo sapiens—especially in the curvature of the skull vault—has an intracranial blood supply system, a lower jaw, and an inner ear structure typical of Neanderthals.”

The skull of Skhul I child showing cranial curvature typical of Homo sapiens

Rewriting the Timeline

For years, Neanderthals were thought to be a group that evolved in Europe, migrating to the Land of Israel only about 70,000 years ago, following the advance of European glaciers. In a groundbreaking 2021 study published in the prestigious journal Science, Prof. Hershkovitz and his colleagues showed that early Neanderthals lived in the Land of Israel as early as 400,000 years ago. This human type, which Prof. Hershkovitz called “Nesher Ramla Homo” (after the archaeological site near the Nesher Ramla factory where it was found), encountered Homo sapiens groups that began leaving Africa about 200,000 years ago—and, according to the current study’s findings, interbred with them. The child from the Skhul Cave is the earliest fossil evidence in the world of the social and biological ties forged between these two populations over thousands of years. The local Neanderthals eventually disappeared when they were absorbed into the Homo sapiens population, much like the later European Neanderthals.

The lower jaw of Skhul I child showing features characteristics of Neanderthals

Advanced Analysis Confirms Hybrid Traits

The researchers reached these conclusions after conducting a series of advanced tests on the fossil. First, they scanned the skull and jaw using micro-CT technology at the Shmunis Family Anthropology Institute at Tel Aviv University, creating an accurate three-dimensional model from the scans. This enabled them to perform a complex morphological analysis of the anatomical structures (including non-visible structures such as the inner ear) and compare them to various hominid populations. To study the structure of the blood vessels surrounding the brain, they also created an accurate 3D reconstruction of the inside of the skull.

“The fossil we studied is the earliest known physical evidence of mating between Neanderthals and Homo sapiens,” says Prof. Hershkovitz. “In 1998, a skeleton of a child was discovered in Portugal that showed traits of both of these human groups. But that skeleton, nicknamed the ‘Lapedo Valley Child,’ dates back to 28,000 years ago—more than 100,000 years after the Skhul child. Traditionally, anthropologists have attributed the fossils discovered in the Skhul Cave, along with fossils from the Qafzeh Cave near Nazareth, to an early group of Homo sapiens. The current study reveals that at least some of the fossils from the Skhul Cave are the result of continuous genetic infiltration from the local—and older—Neanderthal population into the Homo sapiens population.”

Prof. Israel Hershkovitz