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December 5, 2016 / 5 Kislev, 5777

Posts Tagged ‘research’

Tel Aviv U Research: Enzyme Treatment of Gene May Reverse Effects of Alzheimer’s

Thursday, October 6th, 2016

A Tel Aviv University study published last month in the Journal of Alzheimer’s Disease suggests a new possible culprit in causing Alzheimer’s: the APOE gene. Like Dr. Jekyll and Mr. Hyde, APOE has two faces: a healthy form called APOE3 and a disease-related pathological form called APOE4. Now, according to a TAU press release, researchers have developed a novel mechanism and approach with which to convert the “bad” APOE4 to the “good” APOE3.

The research was led by Prof. Daniel (Danny) M. Michaelson, Director of the Eichenbaum Laboratory of Alzheimer’s Disease Research and incumbent of the Myriam Lebach Chair in Molecular Neurodegeneration at TAU’s Faculty of Life Sciences, together with Anat Boehm-Cagan, the Eleanore and Harold Foonberg Doctoral Fellow in Alzheimer’s Disease Research, and in collaboration with the commercial company Artery Ltd., based in California.

For the last 20 years, researchers have focused on amyloid beta peptides and the “plaque” they sprout in diseased brains as the main target of Alzheimer’s research. But the pace of progress in treating — not to mention curing — the debilitating, neurodegenerative disease has been painfully slow.

Prof. Michaelson said that “APOE4 is a very important and understudied target. It is expressed in more than 60 percent of Alzheimer’s patients. Anti-APOE4 treatments are thus expected to have a major impact on the patient population.”

He explained that “the normal APOE gene provides the interface that moves lipids — naturally occurring molecules that include fats, cholesterol, fat-soluble vitamins and other components essential to the health of cells — in and out of cells, whereas the healthy APOE3 does so effectively, the bad form — APOE4 — is impaired.”

Prof. Michaelson and other groups have discovered in earlier research that the bad APOE4 and the good APOE3 differed in their interactions with lipid cargo, so that, for example, the good APOE3 is associated with substantially more lipids than APOE4.

The researchers devised an experimental approach to measure the “bad” features of APOE4, utilizing genetically manipulated mice expressing either good or bad forms of APOE. Mice with APOE4 exhibited impaired learning and memory, damaged brain synapses, and an accumulation of phosphorylated tau and a-beta molecules — two pathological hallmarks of Alzheimer’s. Could there be a way of turning the bad gene good?

“Once this model was established and the pathological effects of APOE4 could be reproduced in mice, we could test therapeutic approaches and tackle APOE4 itself,” Prof. Michaelson said. “Because we know that APOE4 carries fewer lipids, we looked at the means of counteracting the lipidation deficiency.”

“We focused on an enzymatic machinery called ABCA1 that loads lipid cargo onto APOE4,” he continued. “We found that the impaired lipidation of APOE4 could be successfully reversed by activating ABCA1. Most importantly, we discovered that this increased lipidation of APOE4 reversed the behavioral impairments and brain damage seen in non-treated APOE4 mice.”

In the course of administering the treatment, the researchers found that mice which prior to treatment exhibited disoriented behavior and seemed “lost,” following treatment were able to locate a submerged island in the middle of an artificial pond. Mice who had forgotten familiar objects — like Coca Cola bottles — suddenly exhibited sharp object recognition.

“Is there really a magic bullet? One treatment that covers all aspects of Alzheimer’s? Not likely,” said Prof. Michaelson. “Therefore there is a need to define specific subpopulations and to develop treatments targeted at genetic risk factors of the disease, like APOE4, which affects more than half of the Alzheimer’s population.”

JNi.Media

Israeli Researchers Discover Genetic Evolutionary Signature Associated to Autism

Thursday, September 29th, 2016

By Ilana Messika

Israeli researchers say that the discovery of a unique evolutionary signature in genes associated with Autism Spectrum Disorder (ASD) could lead to a better understanding of the genetic nature of the syndrome. That, in turn, could lead to a range of targeted therapies for the condition.

“[Our discovery will] aid in better understanding the biological mechanisms involved in autism development,” said Dr. Idan Menashe, the lead researcher and co-author of The Unique Evolutionary Signature of Genes Associated with Autism Spectrum Disorder, published in Behavior Genetics, a prominent medical industry journal. Speaking to Tazpit Press Service (TPS), Menashe said the discovery would allow scientists to focus on a specific biological target when developing future therapies for autism.

In a study conducted with Mr. Erez Tsur, and Prof. Michael Friger of Ben-Gurion University of the Negev in Be’er Sheva, the researchers found that 651 gene sequences taken from autistic individuals held common characteristics of autism-associated genes in contrast to other disease-related genomes. They said the finding provides an important opening towards understanding the genetic basis of the syndrome.

“The results of this research will help us to target more genes when we test for ASD and consequently expand the spectrum of identified cases,” Menashe said.

According to their research, the genes in question are longer than both healthy genes and genes that are afflicted with other types of abnormalities. In addition, the genes are less susceptible to the evolutionary process of negative selection: ASD are 20 percent less likely to mutate in expected ways over the course of multiple generations compared to other samples of genes.

“Some cases of autism are due to ‘de-novo’ mutations, which are mutations that were developed after fertilization, in the developing fetus,” Dr. Menashe explained.

“Second, some inherited mutations only cause autism when they are associated with other genetic or non-genetic risk factors. Therefore, if the mutations occur in the DNA without any other risk factor, they will not lead to autism and will possibly be passed on to future generations,” he stated.

Currently, ASD is diagnosed according to specific behavioral criteria that are defined by the Diagnostic and Statistical Manual of Psychiatric Disorders (DSM-V). The main characteristics shared by all children with autism are deficits in social communication, and restricted repetitive movements or behaviors.

The ‘Genetic Chip’ is a genetic examination to test few cases of autism already exist. However, although genetics plays a significant role in the disease’s development, there are strong indications for some cases of autism, that other non-genetic factors also contribute to the disorder.

TPS / Tazpit News Agency

Israeli, US Scientists Discover Link to Prevent Breast Cancer Metastasis [video]

Monday, September 19th, 2016

A study led by Tel Aviv University’s Dr. Noam Shomron of the Sackler School of Medicine has discovered that delivery of a combination of genetic therapy with chemotherapy to a primary tumor site is extremely effective in preventing breast cancer metastasis.

The research was carried out at TAU in collaboration with Massachusetts Institute of Technology, led at MIT by Dr. Natalie Artzi, and the students of both principal investigators. Data on human genetics were provided by Prof. Eitan Friedman of TAU’s Sackler Faculty of Medicine and Chaim Sheba Medical Center.

In a TEDxTalk event in August of this year, Dr. Shomron discussed the study with a group of colleagues.

The findings were also published in the September 19, 2016 online issue of Nature Communications.

One in eight women worldwide are diagnosed annually with the disease. Breast cancer is the second leading cause of cancer death among women.

Hana Levi Julian

Israeli Scientists Find Protein in Blood to ID Alzheimer’s Disease

Tuesday, February 9th, 2016

Researchers at Tel Aviv University, Technion, Rambam Medical Center and Harvard University discovered a new biomarker to identify cognitive aging and Alzheimer’s disease.

The new study, published in the Journal of Alzheimer’s Disease, found that levels of “activity-dependent neuroprotective protein” (ADNP) can be easily monitored in routine blood tests. Moreover, ADNP levels in blood tests correlate with higher IQ in healthy older adults.

The research was led by Prof. Illana Gozes, the incumbent of the Lily and Avraham Gildor Chair for the Investigation of Growth Factors. She is also former director of the Adams Super Center for Brain Studies at TAU’s Sackler Faculty of Medicine and a member of TAU’s Sagol School of Neuroscience. It was also spearheaded by Dr. Gad Marshall, Dr. Aaron Schultz, and Prof. Reisa Sperling of Harvard University, and Prof. Judith Aharon-Peretz of Rambam Medical Center – The Technion Institute of Technology. TAU PhD student Anna Malishkevich also participated in working with the team.

Investigators analyzed blood samples taken from 42 healthy adults, MCI (mild cognitive impairment) patients and Alzheimer’s disease patients at Rambam Medical Center in Israel. After comparing the DNP expression in the blood samples, the researchers prepared plasma samples and once again compared the protein levels.

Significant increases in ADNP RNA were seen in patients ranging from mild cognitive impairment (MCI) to Alzheimer’s disease. ADNP levels tested in plasma and serum samples, as well as white blood cell RNA levels, distinguished between cognitively normal elderly, MCI and Alzheimer’s disease participants.

“This study has provided the basis to detect this biomarker in routine, non-invasive blood tests, and it is known that early intervention is invaluable to Alzheimer’s patients,” Gozes said.

“We are now planning to take these preliminary findings forward into clinical trials — to create a pre-Alzheimer’s test that will help to tailor potential preventative treatments. We have found a clear connection between ADNP levels in the blood and amyloid plaques in the brain,” she said.

The researchers are currently exploring larger clinical trials to better determine the ability of ADNP to predict cognitive decline and disease progression.

Hana Levi Julian

Israeli Scientists Create Robo-Locust at Tel Aviv University

Wednesday, January 6th, 2016

A team of Israeli scientists at Tel Aviv University are inventing the Robo-Locust.

No, really.

Lead researcher Professor Amir Ayali of the Department of Zoology at Tel Aviv University’s Faculty of Life Sciences told Reuters he was inspired by the locust’s jumping mechanism.

“The locust, being a large insect that has wonderful jumping performance, offered itself as a wonderful inspiration for this specific idea of a jumping miniature robot,” Ayali explained.

The little robot could possibly be used in the future for surveillance, and maybe for emergency response systems. But additional funding is needed for further development; the research team began the project with just $200,000 USD. More is needed to move ahead.

Made with steel springs, carbon rods and new three-dimensional printed plastic pieces, it is only four inches long (10 cm) and weighs less than one ounce (23 gr). But despite its tiny size, this robot can jump 11.5 feet (3.5 meters) into the air, for 1,000 jumps, due to its lithium battery.

Its motor, structure and energy storage all combine to create the capability of withstanding the long jump, and high acceleration, Ayali said. Because the parts are relatively inexpensive, he estimates the cost per robot at about $100 USD.

The researcher is hoping to develop mechanisms of swarming capabilities in the robotic systems. He is being encouraged by Hungarian-born Dr. Gabor Kosa of TAU’s Faculty of Engineering, who also dreams of a swarm of robo-locusts.

Kosa has a broader vision — a swarm installed with GPS navigation systems, cameras and solar panels for renewable energy – a swarm that can enter enemy territory for surveillance operations.

Kosa is hoping to build a robotic system capable of multiple jumps, with a robo-locust that can spread its wings, and fly.

Hana Levi Julian

Air Quality Improves With New Haifa Bay Environmental Project

Wednesday, January 6th, 2016

The air quality in the area around the Haifa Bay has improved over the past year, according to the Environmental Protection Agency.

The region saw an 11 percent drop in air pollution levels coming from the industrial sector, the agency announced Tuesday, reaching a 65 percent drop since 2009. The first quarter report of a new action plan for the region said 77 percent of the biggest Haifa Bay factories are also now mandated to comply with stricter emissions controls.

Haifa Mayor Yona Yahav called it an “historical day.” For the first time in the history of the state, said the mayor, “a government representative has assumed not only the authority but also the responsibility of the state to correct the distortions and even the crimes committed in the Haifa Bay.”

The figures were presented in the first quarterly report of the National Action Plan for the Haifa Bay Area, a five year plan budgeted at NIS 330 million.

The government approved the project in September, tasking the program to improve the air quality in the region while reducing environmental risks. In addition, the program is being used to promote research, increase accessibility to data and beef up supervision, enforcement and monitoring of environmental issues in the area.

Hana Levi Julian

‘Smart’ Drug Created by Israeli, US Researchers

Wednesday, July 22nd, 2015

Researchers at Ben-Gurion University of the Negev and University of Colorado have created a dynamic new “smart” drug that is sensitive to the degree of inflammation, using a highly novel new approach.

The three describe a novel creative development of an anti-inflammatory engineered protein in the recent edition of the Journal of Immunology.

The uniqueness of this anti-inflammatory molecule can be found in a singular property; while it is injected as a non-active drug, excessive inflammation will activate it. Most other anti-inflammatory agents effectively inhibit inflammatory processes, but in a non-specific manner, and in areas that include sites of necessary normal inflammatory processes. The beauty of this invention lies in the use of a known natural biological code, says Dr. Peleg Rider, a researcher with the BGU Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences. “We mimicked a natural process that occurs during inflammation. The protein is actually a chimera comprised of two domains, both originating from the potent inflammatory cytokine family of IL-1.

“The first part of the protein holds the functional part of the molecule inactive, as occurs in normal living cells, and is connected to a potent natural inhibitor of IL-1.

“Upon encountering inflammatory enzymes, the molecule is cleaved and the functional part becomes active”, Rider explains.

The development is important since inhibition of inflammation in a non-specific manner reduces our natural ability to fight infections. This is a common side-effect of anti-inflammatory biologic therapeutics.

When a non-specific agent is used, any patient who suffers from local inflammation might then also be exposed to opportunistic infections at distant sites, such as lungs — risking, for example, tuberculosis.

This risk is mainly of concern to immuno-suppressed patients as well as older patients and patients undergoing chemotherapy as part of an anti-cancer treatment course, Rider said. He and BGU’s Dr. Eli Lewis and Prof. Charles Dinarello of the University of Colorado used a mouse model of local inflammation to demonstrate that leukocytes, which infiltrate inflammatory sites, indeed activate the chimeric protein, which in turn reduces local inflammation.

The activation of the protein correlated with the amount of inflammatory stimuli. Side effects are avoided because upon resolution of inflammation, the activation of the protein is also reduced.

The new chimeric molecule is protected by patent, owned by BGN Technologies, the technology transfer office of Ben-Gurion University and by the University of Colorado.

The research was supported by the Israeli Ministry of Economy’s Chief Scientist’s Office’s Kamin program.

Hana Levi Julian

Printed from: http://www.jewishpress.com/news/breaking-news/israeli-researcher-at-bgu-creates-smart-drug-with-u-colorado-colleague/2015/07/22/

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