Tag: Medicine

Innovative method to convert waste into disinfectant is a pandemic game-changer

Tel Aviv University Researchers Discover Alzheimer’s-Like Traits in Autistic Child’s Brain

An extensive international study led by Tel Aviv University, headed by Prof. Illana Gozes of the Department of Human Molecular Genetics and Biochemistry, found deposits of the tau protein typically found in Alzheimer’s patients in tissues taken from the postmortem brain of a 7-year-old autistic child. The child suffered from the ADNP syndrome, an ADNP mutation that causes a deficiency/malfunctioning of the ADNP protein which is essential for brain development. The ADNP syndrome child was characterized by severe developmental delay, intellectual disability, and autism. In light of these findings, the researchers tested an experimental drug called NAP – originally developed for Alzheimer’s disease – on nerve cells in a model of ADNP syndrome with the mutation inducing Alzheimer’s-like symptoms. The experiment was a success, with the damaged nerve – like cells returning to normal function.

The study was conducted in close collaboration with researchers from the Blavatnik School of Computer Science at Tel Aviv University, Sheba Medical Center, and a variety of research institutions across Europe, including the biotechnology institute BIOCEV in the Czech Republic, the Aristotle University of Thessaloniki in Greece, the University of Antwerp in Belgium, and the University Hospital Centre in Zagreb, Croatia. The article was published in July 2020 in the journal Translational Psychiatry printed by the Nature Publishing Group.

Prof. Gozes explains that the current study is based on tissues taken from the brain of a 7-year-old boy with ADNP syndrome who died in Croatia. “When we compared the postmortem ADNP syndrome brain tissues to tissue from the brain of a young person without ADNP syndrome, we found deposits of the tau protein in the ADNP child, a pathology that characterizes Alzheimer’s disease.”

The researchers then “treated” damaged nerve-like cells carrying an ADNP mutation, similar to the deceased child mutation with a drug candidate called NAP, which is developed in Prof. Gozes’s laboratory and originally intended to be used to help treat Alzheimer’s disease. “NAP is actually a short active fragment of the normal ADNP protein,” says Prof. Gozes. “When we added NAP to the nerve cells carrying an ADNP mutation, the tau protein bound to the nerve cell skeleton properly, and the cells returned to normal function.”

Prof. Gozes: “The fact that NAP treatment has been successful in restoring the normal function of neuronal-like cell models with impaired ADNP raises hopes that it may be used as a remedy for ADNP syndrome and its severe implications, including autism. Moreover, because other genetic disorders related to autism are characterized by tau pathologies in the brain, we hope that those suffering from these syndromes will also be able to benefit from NAP treatment in the future.” It is important to note that NAP (also called CP201) has been classified as an “orphan drug” by the US Food and Drug Administration, and is currently in the preparatory stages of a clinical trial in children with ADNP syndrome through the company Coronis Neurosciences.

In another phase of the study, the researchers sought to broaden their understanding of the effects of the mutation that causes ADNP syndrome. To do this, they extracted the genetic material mRNA (messenger RNA) from the tissues of the deceased child, and performed an expression analysis of about 40 proteins in the same child, encoded by the mRNA. Full genetic sequencing was also performed to determine protein expression in white blood cells taken from three other children with ADNP syndrome. An in-depth study was carried out on all of the data obtained in the genetic sequencing using advanced bioinformatics computational tools. The data were compared to online databases of protein expression data from healthy individuals, revealing a variety of characteristics that were common to the children with the syndrome, but very different from the normal appearance of these proteins.

Prof. Gozes concludes that “the significance of these findings is that the mutation that causes ADNP syndrome damages a wide range of essential proteins, some of which bind to, among other things, the tau protein, and impair its function as well. This creates various pathological effects in the brains (and other tissues) of children with ADNP syndrome, one of which is the formation of tau deposits, known to be a characteristic of Alzheimer’s disease. The vast and in-depth knowledge we have accumulated through the present study opens the door to further extensive and diverse research. We hope and believe that we will ultimately reach the goal of developing a drug or drugs that will help children with autism resulting from genetic mutations.”

Featured image: Prof. Illana Gozes

Immune System Stimulating Treatment to Reduce Psychological and Physiological Stress Prevents Metastases and Can Save Cancer Patients’ Lives

In a breakthrough research published recently in Nature magazine, Tel Aviv University researchers found that the short time period around the tumor removal surgery (the weeks before and after surgery), is critical for prevention of metastases development, which develop when the body is under stress.

According to the researchers, to prevent development of metastases after the surgery, patients need immunotherapeutic treatment along with treatment to reduce inflammation, and physical and psychological stress. The research was conducted by Prof. Shamgar Ben-Eliyahu from the School of Psychological Sciences and Sagol School of Neuroscience at Tel Aviv University and Prof. Oded Zmora from Assaf Harofe Medical Center.

Immunotherapeutic treatment is a medical treatment activating the immune system. One such treatment, for example, is injecting substances with similar receptors to those of viruses and bacteria into the patient’s body. The immune system recognizes them as a threat and activates itself, thus it can prevent a metastatic disease.

Prof. Ben-Eliyahu explains: Surgery for the removal of the primary tumor is a mainstay in cancer treatment, however the risk of developing metastases after surgery is estimated at 10% among breast cancer patients, at 20%-40% among colorectal cancer patients, and at 80% among pancreas cancer patients.

According to Prof. Ben-Eliyahu, when the body is under physiological or psychological stress, such as a surgery, groups of hormones called prostaglandin and catecholamine are being produced in large quantities. These hormones suppress the immune system cells’ activity, and thus indirectly increase the development of metastases. Additionally, these hormones help tumor cells left after the surgery to develop into life threatening metastases. Thus, exposure to those hormones cause tumor tissues to become more aggressive and metastatic.

“Medical and immunotherapeutic intervention to reduce psychological and physiological stress, and activate the immune system in the critical period before and after the surgery, can prevent development of metastases, which will be discovered months of years later,” stresses Prof. Ben-Eliyahu.

Prof. Ben-Eliyahu adds that anti-metastatic treatment today skips the critical period around the surgery, thus leaves the medical staff to face the consequences of treating progressive and resistant metastatic processes, which are much harder to stop. Prof. Ben-Eliyahu’s research contradicts the assumption, widespread in the medical community, according to which, just like in chemo and radiotherapy, it is not recommended to give cancer patients immunotherapeutic treatment in the month before and after the surgery.

Dan Yamin can detect any kind of contagious outbreak

Research Published in Aging first to Show Enhanced Brain Function and Cognitive Capabilities Resulting from Novel Therapy

Breakthrough method may be applicable to Parkinson’s, Alzheimer’s and more

An international research team, headed by Dr. Tali Ilovitsh from the Biomedical Engineering Department at Tel Aviv University, developed a noninvasive technology platform for gene delivery into cancer cells (breast cancer). The technique combines ultrasound together with tumor-targeted microbubbles. Once the ultrasound is activated, the microbubbles explode like smart and targeted warheads, creating holes in cancer cells’ membranes, and enabling the gene delivery. The two-year research was recently published in the prestigious journal Proceedings of the National Academy of Sciences (PNAS).

Dr. Ilovitsh developed this breakthrough technology during her post doctorate research at the lab of Prof. Katherine Ferrara at Stanford University. The technique utilizes low frequency ultrasound (250 kHz) to detonate microscopic tumor-targeted bubbles. In vivo, cell destruction reached 80% of tumor cells.

Dr. Ilovitsh explains: “Microbubbles are microscopic bubbles filled with gas, with a diameter as small as one tenth of a blood vessel. At certain frequencies and pressures, sound waves cause the microbubbles to act like balloons: they expand and contract periodically. This process increases the transfer of substances from the blood vessels into the surrounding tissue. We discovered that using lower frequencies than those applied previously, microbubbles can significantly expand, until they explode violently. We realized that this discovery could be used as a platform for cancer treatment and started to inject microbubbles into tumors directly.”

Dr. Ilovitsh and the rest of the team used tumor-targeted microbubbles, that were attached to tumor cells’ membranes at the moment of the explosion, and injected them directly into tumors in a mouse model. “About 80% of tumor cells were destroyed in the explosion, which was positive on its own,” says Dr. Ilovitsh. “The targeted treatment, which is safe and cost effective, was able to destroy most of the tumor. However, it is not enough. In order to prevent the remaining cancer cells to spread, we needed to destroy all of the tumor cells. That is why we injected an immunotherapy gene alongside the microbubbles, which acts as a Trojan horse, and signaled the immune system to attack the cancer cell.”

On its own, the gene cannot enter into the cancer cells. However, this gene aimed to enhance the immune system was co-injected together with the microbubbles. Membrane pores were formed in the remaining 20% of the cancer cells that survived the initial explosion, allowing the entry of the gene into the cells. This triggered an immune response that destroyed the cancer cell.

“The majority of cancer cells were destroyed by the explosion, and the remaining cells consumed the immunotherapy gene through the holes that were created in their membranes. The gene caused the cells to produce a substance that triggered the immune system to attack the cancer cell. In fact, our mice had tumors on both sides of their bodies. Despite the fact that we conducted the treatment only on one side, the immune system attacked the distant side as well.”

Potential treatment for brain diseases such as Parkinson’s and Alzheimer’s

Dr. Ilovitsh says that in the future she intends to attempt using this technology as a noninvasive treatment for brain related diseases such as brain tumors and other neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease. “The Blood-Brain barrier does not allow for medications to penetrate through, but microbubbles can temporarily open the barrier, enabling the arrival of the treatment to the target area without the need for an invasive surgical intervention.”

Photo: Dr. Tali Ilovitsh

The project has been awarded a total of 14.9 million EUR; Prof. Dan Peer is leading the mRNA targeting work package.

Dan, What is the research about in the EXPERT project?

What is your and TAU’s part in the project?

What happens now, what is the next step?

Patients with severe COVID-19 develop antibodies faster than those with a mild case of the disease.

Pharmaceutical company Bayer will test new drugs using human heart tissues 3D-printed in Tel Aviv University

Saving precious time

New, innovative drugs