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Hebrew University Researchers Discover Promising Treatment for Aggressive Brain Tumors

Glioblastoma is a serious and incurable brain cancer. Patients who receive this diagnosis typically have 11-20 months to live. One of the main difficulties in treating this cancer is that its cells quickly build up a resistance to chemotherapy. In the upcoming issue of Nucleic Acids Research, Professor Rotem Karni and his team at the Hebrew University of Jerusalem’s Institute for Medical Research share promising results for a new glioblastoma treatment with the potential to improve and extend patients’ lives.

As part of their research, Karni and Ph.D. student Maxim Mogilevsky designed a molecule that inhibits glioblastoma tumor growth by regulating the proteins it produces. The MKNK2 gene produces two different protein products through a process called “RNA alternative splicing.” These proteins have two opposing functions: MNK2a inhibits cancer growth, whereas MNK2b supports cancer growth. Karni’s new molecule shifts the splicing of MKNK2 so that production of the tumor-stimulating protein decreases, while production of the tumor-suppressing protein increases. As a result, cancerous tumors decrease or die-off completely.

HU Professor Rotem Karni and Ph.D. student Maxim Mogilevsky in the lab

“Not only can this breakthrough molecule kill tumor cells on its own, but it also has the power to help former chemotherapy-resistant cells become chemotherapy-sensitive once again,” shared Professor Karni.

In his study, the biological models with human glioblastoma tumor cells that were treated with this new molecule saw their tumors shrink or die off completely, as opposed to the control biological models who were treated with an inactive molecule. “Our research presents a novel approach for glioblastoma treatment. In the future, we’ll be able to tailor treatments for patients based on the amount of cancer-inhibiting proteins that their tumors produce,” added Karni.

A patent for this technology has been registered and granted in the United States and Europe through Yissum, Hebrew University’s R&D company.

 

CITATION: Modulation of MKNK2 alternative splicing by splice-switching oligonucleotides as a novel approach for glioblastoma treatment. Maxim Mogilevsky, Odelia Shimshon, Saran Kumar, Adi Mogilevsky, Eli Keshet, Eylon Yavin, Florian Heyd, and Rotem Karni. DOI: https://doi.org/10.1093/nar/gky921

FUNDING: German-Israel Foundation, Israel Innovation Authority, Israel Science Foundation, Israel Cancer Research Fund, Israel Cancer Association, The Henry & Merilyn Taub Foundation, and the Carol Epstein Foundation.

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Israeli stem cell startup raises $4 million for chemo effectiveness technology

NewStem Ltd., a Jerusalem-based biotech startup with a precision-medicine technology that it says can increase the effectiveness of chemotherapy, said Monday it has raised $4 million in seed financing from a US-based company.

The US firm is Hollywood Media Corp., a shell company whose shares are traded over the counter. On Monday, Hollywood Media, which previously operated in ad sales, said that it is undergoing a strategic transformation via its investment in NewStem, and refocusing on NewStem’s diagnostic technology. The US company is replacing its officers and directors, and intends to change its name to NovelStem International Corp.

The funding in NewStem will be in two stages, with $2 million in cash upfront and the remaining amount depending on milestones. The US firm will get a 20 percent stake in the firm, rising to 30% once the milestones are met and new funds are injected, NewStem CEO Ayelet Dilion-Mashiah said in a phone interview.

 

NewStem is a spin-off of Yissum, the technology transfer company of the Hebrew University.

 

The Israeli startup’s technology can predict patients’ resistance to chemotherapy, allowing for better, targeted cancer treatments and the potential to reduce such resistance, the company says.

Drug resistance is a major cause of treatment failure in cancer chemotherapy. In present clinical practice, resistance to chemotherapy is only recognized after the first course of treatment has been completed, once no major clinical response is observed. In nearly 50% of all cancer cases, resistance to chemotherapy already exists before initiation of the treatment.

Treatment of patients with ineffective chemotherapy results in major health hazards, unnecessary suffering and increased costs.

The company hopes the funding will enable it to get to market with its technology within three years, Dilion-Mashiah said. Because the technology is used for diagnostics support, it does not need all the regulatory permits that are generally required for medications, she explained.

NewStem CEO Ayelet Dilion-Mashiah (Courtesy)

 

NewStem’s technology, developed by its chief science officer Professor Nissim Benvenisty, is based on the harvesting of human haploid embryonic stem cells. These cells enable the company to create cell mutations to test chemotherapies on. The mutations that are not killed by the chemotherapy agents are those that are resistant to the treatment.

This data is fed into a library created by the company. Comparing this database with each patient’s tumor genetic profile will allow for the prediction of resistance to chemotherapy prior to the commencement of treatment, the company said.

With the funding, NewStem now has a “solid long-term partner” and “the capital, expertise and strategic counsel to further advance NewStem’s products and solutions for chemotherapy targeting,” Dilion-Mashiah said.

In addition to NewStem’s in-house development relating to diagnosis od chemotherapy resistance, the company is seeking to use its haploid technology to enter into collaborations with “leading pharmaceutical companies or promising startups” to develop medications for genetic disorders and for reproductive purposes, the company said in a statement.

“NewStem is an excellent new addition to the dozens of academic-born startups rooted in the strong life science research at the Hebrew University,” Yaron Daniely, the CEO and president of Yissum, said. “This investment provides strong support for NewStem’s goal of revolutionizing the treatment of cancer through personalized, patient-centered care.”

Benvenisty is a professor of genetics at the Hebrew University, and the Director of the Azrieli Center for Stem Cells and Genetic Research. His research focuses on stem cell biology, tissue engineering, human genetics, and cancer research.

Yissum serves as a bridge between academic research at the university and the community of entrepreneurs, investors, and industry.

Read the source article at The Times of Israel

Medicine/Health

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New cancer drugs could halt autism symptoms AND prevent their onset by blocking a protein linked to both conditions

Drugs under development for cancer could halt autism symptoms by blocking a protein linked to both conditions, new research suggests.

Unnamed medications that stop the protein ERK2 from reaching the brain reverse autism-like symptoms in mice, a study found.

When given to pregnant rodents, the drugs not only ease the mothers’ symptoms, such as hyperactivity, but also prevent their offspring from being born with the disorder, the research adds.

Lead author Professor Riccardo Brambilla, from Cardiff University, said: ‘It could be possible, in principle, to permanently reverse the disorder by treating a child as early as possible after birth’.

More than 695,000 people in the UK are thought to be on the autistic spectrum. The disorder affects around 1 in 59 children in the US.
How the research was carried out 

The researchers discovered that mice with autism-like symptoms have higher levels of ERK2, which has recently been investigated as a target in cancer treatment.

Such symptoms include reduced maternal actions towards offspring and a decreased sense of smell.

The drugs were given to the mice during their pregnancies.

The researchers plan to conduct a similar trial in autism patients but add it is not ‘feasible’ to treat pregnant women who have been genetically diagnosed with the disorder.

Such patients likely require ongoing medication to treat their symptoms, however, their newborns may benefit from the cancer drugs, they add.

Paracetamol in pregnancy raises children’s risk of ADHD and autism 

This comes after research released last April suggested pregnant women who take paracetamol are up to 30 per cent more likely to have children with attention deficit hyperactivity disorder (ADHD).

The common painkiller, which is also known as acetaminophen, also raises children’s risk of autism by up to 20 per cent, a study found.

Study author Dr Ilan Matok, from the Hebrew University of Jerusalem, said: ‘Our findings suggest an association between prolonged acetaminophen use and an increase in the risk of autism and ADHD.’

Although it is unclear how the drug causes ADHD or autism, paracetamol has previously been linked to communication problems and reduced IQs among children whose mothers took the medication while expecting.

Paracetamol is the active ingredient in hundreds of over-the-counter medications, and is the first-line painkiller for pregnant women to relieve fever and discomfort.

Read the source article at Home | Daily Mail Online

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A higher calling: How Israeli marijuana research changed the world

As much of the world debates how to address marijuana use, the vast majority of American states have legalized it or allow it for medical purposes. Global pharmaceutical companies and hospitals seeking effective treatments using cannabis should look to Professor Raphael Mechoulam, a scientist at Hebrew University. Mechoulam, a pioneer in the field, was the first to isolate, analyze and synthesize the major psychoactive and non-psychoactive compounds in cannabis and has developed a number of revolutionary marijuana-related treatments.

Today, roughly 147 million people use medical marijuana for effective relief of various ailments, including AIDS, multiple sclerosis, Crohn’s disease, cancer treatment side effects and Parkinson’s. Experts believe these numbers will grow exponentially in the coming years, and Mechoulam is now widely recognized as the godfather of medical marijuana, the high priest of his field.

Mechoulam began studying marijuana as a young professor in 1964. He learned that researchers had isolated morphine from opium over 150 years ago and cocaine from coca leaves a century prior, yet no one had tried to understand cannabis and its psychoactive and non-psychoactive ingredients. Mechoulam and his colleagues became their own test subjects and after a few months not only understood marijuana’s ingredients, but found a way to test its medicinal properties.

Not long after Mechoulam’s human experiments with THC, the major psychoactive compound in cannabis, he applied for a grant with the US National Institutes of Health, but the response was not exactly welcoming. “Cannabis is not important to us,” he recalls an NIH official telling him. “When you have something relevant, call us… marijuana is not an American problem.” At the time, not a single US lab was working on it.

In 1965, the NIH changed its tune at the insistence of a member of Congress, who was concerned about his son’s recreational use. Mechoulam had just isolated THC for the first time and discovered its structure. Dan Efron, head of pharmacology at the National Institute of Mental Health, promised Mechoulam financial support for further research. In return, the professor sent the NIH the entire world supply of synthesized THC, about 10 grams, which the NIH used to conduct many of the original cannabis experiments in the United States.

Today, thanks to Mechoulam’s research over the past half century, doctors around the world prescribe marijuana for a variety of disorders. Mechoulam’s work catapulted Israel to the top of the field of medical marijuana testing.

“Israel is the marijuana research capital of the world,” says Dr. Sanjay Gupta, chief medical correspondent for the Health, Medical & Wellness unit at CNN.

Globally, there is an obstacle to wider acceptance of medical marijuana: doctors themselves. Mechoulam believes that use of the drug is not standard practice because most physicians are not yet familiar with it and because most doctors are uncomfortable with a medicine that can be consumed by inhaling its smoke. But Mechoulam has played a major role in dispelling misconceptions about cannabis.

“The problem is that for many years, marijuana was put on the [same] scale as cocaine and morphine,” Mechoulam says. “This is not fair. All drugs, starting from aspirin to valium, [have] side effects. One has to know how to use them.”

Until recently, pharmaceutical companies weren’t enthusiastic about applied research on the drug. The legal ambiguity around cannabis and the difficulty of filing patents on a plant that has existed forever limit their ability to make money.

“It is still widely believed that cannabinoids are drugs and they make you crazy, make you mad, that they don’t have therapeutic value and they are addictive,” says Manuel Guzman, a professor in the Department of Biochemistry and Molecular Biology at Complutense University in Madrid and one of the world’s leading scientists studying the effects of cannabis on cancer cells. But, according to Guzman, that’s “based on ignorance. Knowledge takes time to get absorbed by society and the clinical community.”

At the federal level, cannabis is still illegal in the United States, which prevents serious and ongoing research on THC and on CBD, the non-psychoactive compound in cannabis. But 23 states and the District of Columbia have legalized marijuana for some medical uses, and according to polling data, a majority of Americans now favor legalization for recreational purposes. Elsewhere in the world, there is even more momentum. Israel, Canada and the Netherlands all have medical marijuana programs. Uruguay has legalized pot and Portugal has decriminalized the drug.

All of this gives reason for optimism about the future of medical marijuana research, according to Mechoulam, who is now investigating the drug’s effects on asthma. It is clear that his groundbreaking life’s work and “never, ever give up” attitude are slowly changing the minds of his peers. “If a Nobel Prize was given on cannabis research,” Dr. Guzman says, “Rafi would be the leading candidate.”

The writer is the author of Thou Shalt Innovate: How Israeli Ingenuity Repairs the World (Gefen Publishing) and a senior fellow at the American Foreign Policy Council.

Read the source article at Jpost

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Israel study paves way for women to skip difficulties of first pregnancies

A woman’s body learns from difficulties in a first pregnancy and adapts to try to avert such difficulties in subsequent pregnancies, Israeli researchers said.

The researchers, at Hadassah Medical Center and the Hebrew University of Jerusalem, say their six-year study on the role of certain cells during a women’s pregnancy period may pave the way to develop new drugs to decrease complications in childbirth.

Their research on the “trained memory” of the “natural killer” cells that fight viruses and tumors, they said, found that the cells in charge of helping fetuses implant in the womb and avoid diseases such as preeclampsia or intrauterine growth retardation are more active during a second pregnancy, because they remember the first and are thus better trained to do their job the second time round.

“It is a known clinical fact that second pregnancies are more efficient than first,” Prof. Simcha Yagel, the head of the division of Obstetrics and Gynecology at Hadassah Medical Center, who was on the research team, said in a phone interview with The Times of Israel. Fetuses generally implant better in a second pregnancy; the babies are born bigger and the pregnancy is less prone to diseases such as preeclampsia, a complication that raises blood pressure and causes other damage in the mother.

He said that the new study, published in the journal Immunity, provides a cellular and molecular explanation for this phenomenon.

“If we know why the second pregnancy is better than the first, then maybe we can do something to help women with high risk first pregnancies — like after in vitro fertilization or who are older,” based on this molecular research, he said.

Illustrative image of a baby holding hands (boonchai wedmakawand; iStock by Getty Images)

The study, which lasted more than six years and was based on hundreds of samples of mucous membranes, was led by Moriya Gamliel and conducted with Dr. Debra Goldman-Wohl, together with Prof. Ofer Mandelboim of the immunology and cancer research department of the Hebrew University of Jerusalem, and Yagel.

For their work, the researchers studied Natural Killer (NK) cells — these are cells that are present in the immune system of all of us, men and women, and that are in charge of fighting viruses and tumors.

However, there are also NK cells that are found in the lining of the uterus at the beginning of a pregnancy. These cells are not belligerent, said Gamliel. Rather, they have turned their “swords” into “shovels” and have become “shields,” whose role is to help with the development of the fetus, she said in a statement.

In a pregnancy, these NK cells have two missions, explained Yagel. Their primary role is to help build a successful implantation of the fetus, he said, with the secondary role being that of stopping viruses and other illnesses. Some 70 percent of the cells in the lining of the uterus are NK cells.

Illustrative image of an embryo (Zffoto; iStock by Getty Images)

Their role in the pregnancy is “very important,” he said. They likely originate from the bone marrow of the mother or are present in the endometrium of the uterus – and are triggered into operation at the start of a pregnancy, helping the fetus to survive.

The researchers set out to study if there are differences in the NK cells of first pregnancies versus second ones, and looks like they hit the jackpot. They found a “unique population” of NK cells that is unique to second and repeated pregnancies — which were characterized by a higher number of the receptors — NKG2C and LILRB1– they expressed. They called these cells the “Pregnancy Trained” NK cells.

“For many years researchers thought that NK cells didn’t have a memory,” said Yagel. “But our research found that they do have memory.” During the study, the researchers found that in each recurrent pregnancy — that is, not the first pregnancy but in subsequent ones — the NK cells remember the first pregnancy experience and improve their function the next time. There was no difference however between the performance of these cells between the second and subsequent pregnancies, Yagel said.

The NK cells in a second or third pregnancy remember the first pregnancy and are “better prepared” for the job, he said. They act faster and more effectively. They wait for the trigger “to produce the goodies needed for a successful pregnancy.” This memory remains both between pregnancies and during pregnancies, he said.

The first pregnancy “paves the way for the second one,” Yagel said. The findings are somewhat counterintuitive, he said, as one would expect the first pregnancy to get the best shot, paving the way for the others. It is still not clear “why nature, or God, built us in this way,” he wondered.

The key then, is to get through the first pregnancy, and others will be better.

This insight may help researchers find a way to “skip” the difficulties of the first pregnancy and help train the NK cells from the start, he said, paving the way for the development of new drugs to treat diseases of poor implantation.

Read the source article at The Times of Israel

News

Koalas, horses and pygmy goats (oh my!) in Israeli-UC Davis vet team-up

A list of the collaborative work between the UC Davis School of Veterinary Medicine and the Koret School of Veterinary Medicine — the only veterinary school in Israel — reads something like a “who’s who” of the animal kingdom.

Nearly 65,000 cats, dogs, horses, cows and goats (including pygmy and Nubian varieties) are cared for annually at the Davis and Rehovot facilities, along with the occasional gorilla, koala and wallaby.

Though 7,300 miles apart, the universities have been collaborating on research, grants, academic papers and faculty exchanges for more than three decades, thanks to support from an endowment at the S.F.-based Koret Foundation.

Read the source article at jweekly.com

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The pomegranate potential

Pomegranates are known to contain powerful antioxidants that fight the oxygen free radicals that cause inflammation, accelerated aging of the tissues, the activation of harmful genes within DNA and an overloaded immune system. Various herbs, spices such as turmeric and teas, as well as dark chocolate, pecans, fruits like blueberries, goji berries, elderberries, cranberries, blackberries and vegetables and pulses like sweet potatoes, broccoli, artichoke and kidney beans also reduce the effects of oxidative damage in the body.

The leading health problems facing us today – including conditions like heart disease, cancer, dementia and other neurological diseases – have been linked to increased levels of oxidative damage.

But until now, there has been no natural, powerful antioxidant capable of crossing the “blood-brain barrier” (BBB) – the semi-permeable, highly selective membrane of endothelial cells that separates the circulating blood from the brain and extracellular fluid in the central nervous system. While the BBB is a vital mechanism for protecting the brain from fluctuations in plasma composition and from substances that can upset neural function, it also keeps out those that can benefit the brain.

Punicic acid (Omega 5) found in oil made from pomegranate seeds (not the red fruit but the small, hard seeds inside) is among the most powerful natural antioxidants, but to breach the BBB, it had to be turned into a submicron self-emulsion formulation.

Researchers headed by experimental neurology Prof. Ruth Gabizon at the neurology department at Hadassah University Medical Center in Jerusalem’s Ein Kerem, along with Prof. Shlomo Magdassi of the Hebrew University’s Nanotechnology and the Casali Center for Applied Chemistry, have developed a food supplement called GranaGard with high concentrations of punicic acid. This substance converts in the body into conjugated linoleic acid, an established neuroprotector. Hadassit, the Hadassah Medical Organization’s research and development arm, and Yissum, the R&D company of the university, established Granalix. This company markets the supplement (it is made by the SupHerb company in Nazareth), which has been approved by the US Food and Drug Administration (FDA). The supplement (NIS 120 for 60 capsules, a month’s supply, and sold via the company’s website and at some stores) is aimed at preventing or slowing the development of neurological disorders from multiple sclerosis to dementia and even reducing symptoms in patients who suffer from them. As GranaGard is a food supplement, it cannot legally make therapeutic claims, but it can provide data on mice studies in which the rodents showed significant improvement in neurological conditions and benefits shown in patients who have taken the supplement over time.

GABIZON, WHO was born in Argentina and came on aliya with her family at the age of 11, is married to Prof. Alberto Gabizon, chief of the oncology institute at Jerusalem’s Shaare Zedek Medical Center, and they have four grown children.

“We met at the Weizmann Institute of Science. I am not a physician, but a neurology researcher,” she said in an interview with The Jerusalem Post. She did a post-doctoral fellowship at the University of California at San Francisco with Prof. Stanley Prusiner, an American neurologist and biochemist who discovered prions – a class of infectious self-reproducing pathogens primarily or solely composed of protein – for which he received the Nobel Prize in Physiology or Medicine in 1997.

“It was very serendipitous, as I had read Prusiner’s articles on prions and then met somebody by chance who was on sabbatical at the university. I sent a letter to Prof. Prusiner, and I was accepted to work at his lab. I was in the right place at the right time, as he was doing totally pioneering work.”

When she returned to Israel in 1988 and continued her research on prion-caused diseases in the lab she built at Hadassah’s neurology department, she did not work on theoretical research detached from the physical disease. “I was part of the clinical department, exposed to patients and their families.”

GABIZON HAS devoted most of her career to the study of neurodegenerataive and prion disorders, including Creutzfeldt-Jakob disease (CJD), a genetic disease among Jews of Libyan and Tunisian origin that was identified in Israel in the 1980s. The incidence of the disease in this ethnic group is about 100 times more than in the worldwide population, and there are some 50,000 carrier families in Israel and 15 actually suffering from the disease. Its effects were similar to the “mad-cow disease” (bovine spongiform encephalopathy) that affected cows whose brain and spinal cord had been contaminated in Britain and killed its first victim there in 1995.

Genetic CJD is vertically transmitted from parent to child in autosomal dominant inheritance. Gabizon noted that there have also been some sporadic cases among Jewish of Ashkenazi origin.

“A young man or woman in their 30s, at the beginning of their life, have just finished their studies and started on a career, got married, and are raising kids. In the midst of this intensive endeavor – a mother or father, perhaps an uncle, becomes ill. The patient is not particularly old, in his 50s or 60s, and is still very much active – with future plans and unattained goals. Yet the disease is progressing at an alarming rate. At first, the patient doesn’t remember small details or his speech slurs. He gets lost in a familiar neighborhood, loses balance. Something is happening; something is festering. He visits his family doctor and then a neurologist, undergoing CT or MRI; his condition continues to deteriorate relentlessly. And then the patient is no longer really with us, even if he or she still lives a bit longer. This is of course shocking and very sad. But it is just the beginning of the story.”

In the midst of all this mayhem, “the specialist asks: ‘Are you from Libya or Tunis?’ Then there are genetic examinations. Thus our man or woman, still in their 30s, and their entire family, find out that their family member is afflicted with a hereditary disease.”

There is a mutation that causes an important protein in the brain to change its form, so that instead of breaking down when it has completed its role, it oxidizes and is stored in brain cells in clusters called amyloids. As a result of the accumulation of clusters of faulty protein, destructive free radicals are created, damaging the quality of the cells. Ultimately, a process of accelerated destruction of the cells is created by this combined co-dependent process, in which protein does not break down, but rather accumulates in clusters, thus creating free radicals that harm the quality of the brain cells.

“Most people who are CJD carriers don’t want to know because the symptoms show up after the age of 40, and there is nothing to do for them. They become confused, very nervous and then paralyzed. They usually die within three months of diagnosis. There is no approved blood test for it,” she said. “But if a couple suspected of being carriers plan to have a baby, they usually want to test embryos by in-vitro fertilization and then use preimplantation genetic diagnosis (PGD) to find unaffected embryos that could be implanted.”

“In view of the dead end reached by all researchers in treating the disease, we decided at the lab to tackle the problem from a totally different direction. If we cannot ‘clean’ the brain cells of destructive faulty protein clusters, thereby curing the patients, perhaps we can strengthen their durability, extend the life span of brain cells, and improve their functioning even under dire conditions such as these, with all of the ‘biological garbage’ and the destructive oxidizing free radicals.”

To this end, “we decided to research the influence of antioxidization on the brain cells, through lab mice in which we planted the Libyan mutation of the PRP protein. The research hypothesis was that if we treat them with sufficiently strong antioxidization that can reach the brain, this may protect the cells and compensate for the damage already incurred. We further stipulated that the treatment should be completely safe of side effects, in order to offer it to young carriers before the disease erupts, as a preventive measure used over many years with no risk involved.”

Her prion research led Gabizon to look for antioxidants connected to lipids that could cross the BBB and reach the brain. “By chance, I bought face cream from the Israeli cosmetics company Lavido that was made from pomegranate oil. People said how young I looked. The Chinese, by the way, discovered long ago that pomegranate seeds were good to eat.”

She called the head of the company and asked for a sample of the oil. “We gave it to mice with the Libyan mutation. We saw that it postponed the mice’s death somewhat, but not enough.” So Gabizon went to Magdassi, who prepared a nano formula with tiny particles and two emulsants. When mixed with water, it turns white. The emulsion isn’t destroyed in the stomach and liver; it goes directly to the blood and breaches the BBB. We started to give it to multiple sclerosis patients after it was effective in slowing the animal model of the disease in mice. We also gave it to mice models with Alzheimer’s disease and to healthy mice that we caused to get a stroke.” It is also being tested on Parkinson’s disease.

“We can’t cure these neurodegenerative diseases, because when neurons die, they can’t be restored. But the supplement can help prevent the disease in people at risk. I have two capsules a day for two years, and so has my husband. I find the supplement improves my sharpness of thinking and gives me much more energy. There are no known side effects or harmful interactions with drugs. The supplement is comprised of 90% pucinic acid in a form that can enter the brain.”

GRANALIX, JUST at the beginning of its marketing effort, sells some 5,000 containers a month, mostly through the Internet. “It costs NIS 10 to manufacture and sells for NIS 120; most of the income goes towards manufacture, salaries and other expenses. We also redirect profits into expanding our research,” said Gabizon, who does not yet profit from the patent held by Yissum and Hadassit registered three years ago. “We don’t want it to be expensive and prohibitive to most people who can benefit from it.”

To register GranaGard as a pharmaceutical drug, the company would have to spend a fortune on large, time-consuming clinical trials and fees for applications to the FDA. “We could do this at some point,” but it is very complicated. In the meantime, since GranaGard is a safe food supplement, we ask patients taking it how they feel. Some report improvement in a month or even a week of taking the supplement.”

The food supplement’s efficacy in the form of nanodrops taken by rodents with a multiple sclerosis model, CJD and metabolic disorders was proven in three articles in scientific journals, the International Journal of Nanomedicine, Nanomedicine and Neurobiology in Disease. GranaGard was shown to delay disease onset in a mouse model of genetic prion disease, which presents neurodegenerative features reminiscent of Alzheimer’s disease. It also was shown to reduce the disease burden in a mouse model of multiple sclerosis. “There are many other studies on the way,” she said.

“Alzheimer’s and Parkinson’s disease seem to be prion-like diseases with aggregation and oxidation, so punicic acid with this delivery system could be effective, without being destroyed in the stomach and liver,” she added.

Neuropaths recommend pomegranate oil to people, but they don’t take into account that it can’t help against neurodegenerative diseases because it doesn’t reach the brain in the form or ordinary supplements.”

IF THE formulation can delay Alzheimer’s disease, it would bring about a revolution, she declared. The International Alzheimer’s Association has reported that by 2030, the number of dementia patients will double, reaching about 70 million worldwide. Global expenditure on treatment has now reached $600 billion, 70% from Western Europe and North America alone.

In Israel, there are now some 120,000 dementia patients, including 1% of the population in their 60s. This percentage is doubled every five years, reaching 30% for ages 85 to 90 and 66% of those over 90.

This data is even more alarming in view of solutions offered by medicine (nowadays appearing quite ordinary – such as nutrition, cholesterol, diabetes, blood pressure issues and hygiene) that have increased life expectancy and created a new demography, she added. ‘The various degenerative brain diseases harm half of the population over 80 and cause significant mental and physical suffering. A cure has yet to be found for the disease, but our nutritional supplement may prevent it.”

The common cause of all degenerative brain diseases is pathological oxidization of components in the nerve cells, which is the precise point of departure of GranaGard. “Since there is no reversal for highly faulty nerve cells, the treatment focuses on maintaining the existing ones, that is, maintaining our brain cells for as long as possible,” she concluded.

Read the source article at Jpost

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Meet Hebrew University’s top cannabis researcher

Attorney General Jeff Sessions unwittingly has become a key supporter of Israel’s thriving medical marijuana industry. Just ask cannabis researcher Yossi Tam.

Speaking in Palo Alto this week, the Israeli expert on cannabinoids — chemicals that give the cannabis plant its medical and recreational properties — said anti-pot politics in the United States have allowed Israel’s medical marijuana industry to thrive. Israel even has attracted some of the top American researchers, he said.

Israel even has attracted some of the top American researchers, he said. After all, in the U.S., marijuana remains a Schedule 1 drug, alongside heroin and ecstasy, meaning that research is stunted because such substances have “no currently accepted medical use and a high potential for abuse.”

However, in Israel, which is preparing to start issuing export licenses for cannabinoid-based products, cannabis research is flourishing. Tam is focused on how cannabinoids can help patients battle obesity, and he’s also part of a team seeking medicinal uses of cannabis in fighting everything from epilepsy to traumatic brain injury to cancer.

“Israel has become a leader because it was allowed to conduct research, whereas here [in the U.S.] it was stopped,” Tam told J. after his talk, which focused on the science of cannabinoids and how to use them to fight obesity. “Once it will be legal here, then the U.S. will take over like with every other thing.”

Tam is the managing director of the Multidisciplinary Center on Cannabinoid Research at the Hebrew University of Jerusalem, and he also heads the Obesity and Metabolism Laboratory there.

He spoke Jan. 16 in Palo Alto at the Morgan, Lewis and Bockius law firm, telling an audience of about 50 that medical marijuana was first used in China nearly 5,000 years ago and that synthetic cannabinoids could have an even wider range of curative powers. The talk was presented by the California Israel Chamber of Commerce, American Friends of the Hebrew University and WGD Partners, a Palo Alto-based financial advisory firm.

Recreational use of marijuana is banned in Israel, but medical marijuana is legal there — and Israeli researchers have been focused on the efficacy of cannabinoids in fighting pain and disease for more than 50 years. Meanwhile in the U.S., Sessions has spearheaded a federal drive to keep pot illegal, even as California this year became the eighth state to legalize recreational use of marijuana and more than half the states allow the use of medical marijuana.

Tam works at Hebrew University with Raphael Mechoulam, who in the 1960s first isolated CBD and THC, the two most prominent of the many cannabinoids found in marijuana.

A brochure available at his talk proclaimed: “Join the cannabis revolution: Cannabis is no longer just associated with getting high, but is now tantamount to getting healthy.”

Michael Mitgang, WGD’s managing director, gave a short presentation on the cannabis industry and its growth potential before Tam’s talk, predicting the $8.1 billion U.S. cannabis market in 2017 will balloon to more than $100 billion annually in a few years.

Tam, a former dentist who did postdoctoral work in the U.S. at the National Institutes of Health, said Israeli researchers know their place at the forefront of cannabinoid investigation will be threatened if the U.S. reclassifies marijuana.

“We have a window of opportunity now,” he said. “Let’s see what happens.”

Read the source article at jweekly.com

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13 of the biggest health breakthroughs in Israel in 2017

Compound kills energy generating system of cancer

An Israeli researcher devised a synthetic compound to disable the enzymes that allow cancer cells to metastasize. When cancer cells leave the primary tumor and spread to other organs, they reprogram their energy-generating system in order to survive in harsh conditions with a shortage of nutrients like glucose. Prof. Uri Nir of Bar-Ilan University identified an enzyme called FerT in the energy-generating mitochondria of metastatic cancer cells – an enzyme normally only found in sperm cells (which need to function outside the body they came from). When he targeted FerT in lab mice, the malignant cells soon died. Using advanced chemical and robotic approaches, Nir’s lab team developed a synthetic compound, E260, which can be administered orally or by injection, causing a complete collapse of the entire mitochondria “power station.” “We have treated mice with metastatic cancer and this compound completely cured them with no adverse or toxic affect that we can see,” reported Nir, adding that normal cells were not affected. Phase 1 clinical trials are planned over the next 18 months. 

Personal menu to help avoid diabetes

In 2015, two researchers from the Weizmann Institute of Science in Israel released a groundbreaking study showing that specific foods and food combinations affect each individual’s blood-sugar level differently.

That discovery was incorporated into a made-in-Israel app, DayTwo, which helps pre-diabetics and diabetics who are not insulin dependent choose dishes that can best balance their individual blood-sugar levels. The algorithm predicts blood-glucose response to thousands of foods based on gut microbiome information and other personal parameters.

High blood sugar is linked to energy dips, excessive hunger and weight gain as well as increased risk of metabolic diseases such as diabetes and obesity.

To use the app, which went on sale in the US in 2017, users need to answer a questionnaire about their medical history, physical characteristics, lifestyle and diet. A stool-sample kit is then FedExed to the user, who sends it on to DayTwo’s lab. There the microbiome DNA is sequenced and the data is plugged into an advanced machine-learning algorithm.

In about six to eight weeks, users receive a microbiome report and a six-month plan of personalized meal recommendations to help balance blood sugar.

World’s first bone implants

In August and December, doctors at Emek Medical Center in Afula performed rare bone implants – one on a man missing part of his arm bone and the second on a man missing five centimeters of his shinbone, both as the result of car accidents. Normally, the human body cannot restore bone segments, but revolutionary tissue-engineering technology developed by Haifa-based Bonus BioGroup enables growing semi-solid live bone tissue from the patient’s own fat cells. The tissue is then injected back into the patient’s body in the expectation that the missing bone fragment will be regenerated in around six weeks without any danger of implant rejection or the complications of traditional bone transplants. “This surgery is truly science fiction; it changes the entire game in orthopedics,” said Dr. Nimrod Rozen, head of orthopedics at Emek, who carried out the experimental procedure. In the future, the Bonus BioGroup regeneration technology could be used for a variety of bone-loss conditions, including bone cancer, for which there is currently no solution.

Artificial cornea

An early-stage Israeli ophthalmic medical devices startup developed a revolutionary artificial cornea implant that holds out hope to millions of blind and visually impaired people. The nanotech-based synthetic cornea by CorNeat Vision of Ra’anana proved successful in initial tests on animals. The company plans human implantations in Israel in mid-2018, and a larger clinical trial in the United States. According to the World Health Organization, diseases of the cornea are the second leading cause of blindness worldwide, affecting as many as 30 million people. “Unlike previous devices, which attempt to integrate optics into the native cornea, CorNeat’s implant leverages a virtual space under the conjunctiva that is rich with fibroblast cells, heals quickly and provides robust long-term integration,” said CorNeat Vision’s Almog Aley-Raz. The surgical procedure takes just 30 minutes. 

Hernia surgery just got simpler

In June, ISRAEL21c reported on a new tool developed by Via Surgical for attaching mesh to tissue, allowing surgeons to treat hernias with fewer complications, less pain and faster recovery. In the US alone, some five million people have a hernia – a protrusion of an organ or tissue through a weak spot in the abdomen or groin — according to the National Center for Health Statistics. Traditionally, open hernia-repair surgery involved stitching a mesh patch, or surrounding tissue, over the weak tissue. Today, many hernias are repaired laparoscopically, but because suturing through tiny laparoscopic incisions is difficult, most surgeons use a less ideal solution — screw-like tacks to secure the mesh to the abdominal wall or bone. Via Surgical’s unique FasTouch cartridge system, which received FDA approval in 2016, affixes prosthetic material to soft tissue. It is designed like sutures and delivered like tacks, with the goal of providing the best of both worlds for laparoscopic hernia repair. “Surgeons are very excited about it,” says Lena Levin, cofounder and CFO of Via Surgical. “Hernia repair is one of the most common surgeries.

Screening newborns for autism

Israeli engineer Raphael Rembrand developed a simple noninvasive way to screen newborns for signs of autism using the same instrument currently used to test infants’ hearing. The SensPD diagnostic test, now ready for clinical trials, uses optoacoustic emissions as an indicator of the baby’s overall sensory perception. It can be administered hours after birth, and because the inner-ear mechanism develops in the third trimester of pregnancy, one day it may even be possible to screen for autism spectrum disorders prenatally. Some three million children are diagnosed with autism every year. The earlier the condition is detected the better the possible outcome. Thirty years ago, Rembrand’s four-year-old son was diagnosed as autistic, but it was too late at this point for critical early-intervention therapies. “Applying interventions before the age of two results in better than 90% success rate in ingraining social skills for social integration,” says Rembrand.

Reversing cognitive decline with cannabis

In May, scientists from the Hebrew University of Jerusalem and from the University of Bonn in Germany announced that they had restored the memory performance of lab mice to a juvenile stage by administering a small quantity of THC, the active ingredient in cannabis. The report in Nature Medicine showed that after giving low doses of THC to mice over a four-week period, the cognitive functions of 12- to 18-month-old mice treated with cannabis were just as good as the functions of two-month-old mice in the control group. Clinical trials on humans are to follow. A study by Therapix Biosciences presented in September to the International Association for Cannabinoid Medicines’ Conference on Cannabinoids in Cologne, Germany, similarly suggested that THC can significantly reverse age-related cognitive impairment in old mice.

Early diagnostic test for Parkinson’s

This year, Hebrew University of Jerusalem Ph.D. student Suaad Abd-Elhadi won the Kaye Innovation Award for her diagnostic tool, ELISA, which detects Parkinson’s disease at a much earlier stage than existing tools, and better tracks progression of the disease and response to therapy. Parkinson’s disease, affecting seven to 10 million people worldwide, is characterized by stiffness, tremors and shaking. Medication to control symptoms is costly. Currently there are no standard diagnostic tests for Parkinson’s other than clinical information provided by the patient and the findings of a neurological exam. Once Parkinson’s is revealed, the neurodegenerative disease is usually already progressing. Abd-Elahdi’s diagnostic tool detects the alpha-synuclein protein closely associated with Parkinson’s disease, and could lead to a minimally invasive and cost-effective way to diagnose the disorder in time to improve the lives of patients. Abd-Elhadi has demonstrated a proof of concept and is analyzing a large cohort of samples as part of a clinical study. Through its Yissum technology transfer company, Hebrew University has signed an agreement with Integra Holdings for further development and commercialization.

Hip-Hope cushions falls in elderly

Each year, nearly 3 million seniors worldwide are hospitalized due to hip fractures – many experiencing a drastic deterioration in quality of life. The direct annual cost of treating hip fractures exceeds $15 billion in the US alone. Rather than focus on better ways to treat the broken bone, Israeli engineer Amatsia Raanan decided to use cutting-edge technology to avoid injury in the first place. He and three cofounders developed Hip-Hope, a smart wearable device designed as a belt. Once Hip-Hope’s multi-sensor detection system senses an impending collision with a ground surface, two large airbags are deployed instantly from each side of the belt to cushion the hips, and a connected smartphone app sends an automatic alert message to predetermined recipients. The 1-kilo (2.2-pound) device, due to go on sale shortly, even has a built-in emergency call button that the user can activate in any situation of distress. Hip-Hope is certified by the CE (Europe), FDA (United States), Health-Canada and AMAR (Israel). In studies carried out at a major Canadian lab, the Israeli device was proven to reduce impact by 90%.

An injection that melts fat

Jerusalem-based Raziel Therapeutics has developed an injection that melts fat cells and postpones the proliferation of new fat cells. The medication generates heat to use up some of the free fatty acid that’s produced by fat cells in the body, which in turn reduces fat tissue. Obesity has become a worldwide epidemic, and the World Obesity Federation predicts that by 2025, a third of the world’s population will be overweight or obese. Raziel’s technology, which targets specific areas in the body, is now in clinical trials in the US. Preliminary results show a 30 to 50 percent reduction in subcutaneous fat at the treated site after a single injection. Each treatment lasts between six and nine months, but treatment could be more effective in those who change their lifestyle in parallel. An audio-analysis technology developed at Ben-Gurion University can assess sleep disorders such as obstructive sleep apnea (OSA) while the user is awake, at home and not hooked up to machines or sensors. The American Sleep Apnea Association estimates that 22 million Americans suffer from the malady and that as many as 80% of moderate to severe OSA cases go undiagnosed. Currently, patients are diagnosed using overnight polysomnography (PSG) to record brain waves, blood oxygen level, heart rate, breathing, and eye and leg movements via electrodes and sensors. The new system, which does not require contact sensors, could be installed onto a smartphone or other device that utilizes ambient microphones. It analyzes speech during waking hours and records and evaluates overnight breathing sounds using new technology that is simpler and significantly less expensive than PSG. The researchers have tested the system on more than 350 subjects and are working toward commercialization. 

First implant for heart failure

In July, a 72-year old Canadian man became the world’s first recipient of an Israeli-developed implant to treat diastolic heart failure – a fairly common condition for which there is no effective long-term treatment. The minimally invasive surgery was performed at Rambam Health Care Campus, a medical center in Haifa. The CORolla implant was developed by cardiologists at Israeli startup CorAssist Cardiovascular of Haifa. The elastic device is implanted inside the left ventricle and applies direct expansion force on the ventricle wall to help the heart fill with blood. The patient, Robert MacLachlan, had run out of treatment options in Canada for his diastolic heart failure. His wife read about CORolla on the Internet and contacted Rambam. 

Renewing damaged cells

Researchers from the Weizmann Institute of Science discovered a molecule in newborn hearts that appears to control the process of renewing heart muscle. The findings, published in June in Nature, point to new directions for research on restoring the function of damaged cardiac cells. Heart disease is the leading cause of death worldwide. The Agrin molecule seems to “unlock” the renewal process and enable heart-muscle repair – never seen before outside the womb. Normally, after a heart attack the damaged muscle cells called cardiomyocytes are replaced by scar tissue, which cannot pump blood and therefore place a burden on the remaining cardiomyocytes. Following a single injection of Agrin, damaged mouse hearts were almost completely healed and fully functional. Scar tissue was dramatically reduced, and replaced by living heart tissue that restored the heart’s pumping function. The research team has begun pre-clinical studies in larger animals.

Read the source article at ISRAEL21c

News

Tiny fish swims to Israel to help unlock mystery of aging

The search for the proverbial fountain of youth is moving underwater. Experimental biologist Itamar Harel, returning to Israel this spring from a post-doc at Stanford University School of Medicine, will establish an aging research lab focused on the tiny East African turquoise killifish, the shortest-lived vertebrate that can be cultivated in the laboratory easily.

Gleaning insights into human aging from a fish that lives an average of four to six months sounds counterintuitive. But the East African turquoise killifish has an aging progression remarkably similar to ours, making it perfect for studying human aging in a rapid timeframe.

“In the past 25 years, experiments in short-lived yeast, worms and flies have revolutionized the way we perceive aging – revealing that the aging rate itself can be manipulated by genetic and environmental interventions,” Harel says.

“However, the lack of short-lived vertebrate models for genetic studies has significantly limited our understanding of vertebrate aging, including the role of vertebrate-specific genes, organs and physiological processes.” At Stanford’s Brunet Lab, Harel used a new genome-editing technique called CRISPR to develop a tool for examining aging and disease in killifish.

Harel’s own lab, to open in March 2018 at the Hebrew University of Jerusalem’s Institute of Life Sciences, will take this research to the next level.

“The key aspect I’m trying to accomplish is to see if we can slow down some of the age-associated diseases we have and extend good health, even if we live the same amount of years,” Harel tells ISRAEL21c.

“I envision using killifish as a platform for testing the role of specific drugs and their effect on age-associated pathologies such as cancer, diabetes, cardiovascular and neurodegenerative diseases,” he says.

“Manipulating the aging rate itself might allow us to postpone the onset of these devastating diseases, which will have a tremendous impact on human health.”

The 37-year-old scientist got his undergraduate degree at Ben-Gurion University of the Negev in 2005 and his PhD in developmental biology at the Weizmann Institute of Science in 2012.

When he arrived at Stanford in 2013, he was fascinated to learn about the killifish, which has been bred in captivity since 1968 but had never been genetically engineered.

The tool he developed using CRISPR enabled him to study the effects of early interventions on elderly killifish.

“I was able to do it almost twice as fast as in parallel genetic models like mice, which have a lifespan of two to three years,” he says. In his Jerusalem lab, he will study aspects of aging unique to vertebrates.

“The majority of aging research has been done on invertebrates, in which it is challenging to study things like bone degeneration, declining immune function, declining ability to benefit from vaccinations, and increasing susceptibility to cancer and infections,” says Harel.

“I think my uniqueness will be to study specific niches that are exceptionally challenging or impossible to study using current models.”

To start, Harel will investigate dyskeratosis congenita syndrome, which causes bone-marrow failure.

“The killifish model shows rapid onset of this disease and I want to see if we can develop interventions to slow down some of these phenotypes, screen for drugs and do genetic interventions.”

People have studied this syndrome in mice but you have to breed them for three to four generations before the phenotypes develop.

In killifish, the phenotype happens in the first generation, and as fast as only two months.” In the long term, Harel hopes the little fish will reveal why aging is the primary risk factor for every disease type. “We know different organisms live vastly different lifespans.

Killifish live six months, while koi fish live up to 200 years,” he says.

“Nature has fabulously played with this trait of the aging rate. If we understand the basics behind the differences we could potentially manipulate them ourselves and see what aspects make the body more susceptible or more resilient.” He isn’t trying to make killifish live as long as koi fish.

“But we could tailor specific interventions to boost our ability to cope with Alzheimer’s or other degenerative diseases,” says Harel, whose family history does not include any centenarians that he knows of. Harel notes that aging research is advanced in Israel, with multiple aging-related research labs doing groundbreaking work.

The Israeli Ministry of Science and Technology recently issued a call for “technologies and innovation for older persons,” including biomedical research on aging.

In October, Israeli longevity expert Dr. Nir Barzilai from Albert Einstein College of Medicine in New York gave a keynote address, “How to die young at a very old age,” at the Pathways to Healthy Longevity conference at Bar-Ilan University sponsored in part by the Israeli Longevity Alliance.

Harel was on the judging panel that awarded prizes to graduate students studying the biology of aging, healthy longevity and quality of life.

“Doing research in Israel comes with a sense of community and ease of developing new collaborations,” says Harel. “For me it was clear that I wanted to go back.”

Read the source article at ISRAEL21c

News

Joint Israeli-US research distinguishes cancerous cells from healthy ones

A protein “switch” that activates the immune system to attack cancer cells when it detects signs of the disease has been developed by researchers from the Massachusetts Institute of Technology and the Hebrew University of Jerusalem.

The switch stimulates an immune response only when it detects the cancer cells, without harming other healthy tissues, the researchers said.

The important discovery has just been published in the journal Cell.

Immunotherapy is now seen as having great potential in the research effort to develop drugs against a wide variety of cancers. Despite this success, the use of immunotherapy remains limited due to the lack of antibodies specific to the tumor of substances that can cause an immune response to a particular type of cancer.

The toxicity of certain treatments, such as systemic therapy for the whole body, for example, is another obstacle. In addition, the treatments do not work in all cases; only about 30% to 40% of patients will respond positively to treatment, even with the most advanced drugs.

As a result, oncology researchers have been trying to develop integrated therapies of various kinds that serve to increase the immune response to damage the cancer cells accurately and specifically by directing the immune system to attack only cancer cells. But to activate the immune system against the tumor, but not against the healthy tissue, a sophisticated mechanism was needed to distinguish between them.

In a research collaboration between MIT and HU and headed by Dr. Yuval Tabach in Jerusalem, the researchers developed a method for finding short sequences of DNA that differentiate cancer cells from healthy tissue. The research itself was conducted by Dr. Lior Nissim, MIT researchers, and Doron Stop, an HU doctoral student who is also a medical student in the Jerusalem faculty.

These DNA sequences, called “promoters,” react to an existing state of the cell and change it by expressing proteins that are suitable for it – for example, in a situation of heat stress.

The team found that naturally occurring proteins in cells do not distinguish well between cancer cells and healthy cells. The researchers then developed a method that enables the design of promoters that discriminate between cancer cells and healthy cells.

They are continuing to develop them with DNA sequencing and using machine-learning algorithms to distinguish between them thus creating a “guided missile” that attacks only malignancies. To the missile, various methods of killing cancer cells could be added, including an immunotherapeutic “Trojan horse” approach.

“We are in the midst of a huge and growing revolution in which computers, biology, and engineering will join together to change medicine,” said Tabach. “Israeli academia has an essential part in the process. This project and others like it will enable targeting in the near future of a specific cell, and killing it either with the immune system or by initiating cell suicide.”

To do this, the research team built a genetic circuit, encoded in DNA, to differentiate cancer cells from non-cancer cells. The circuit, which can be customized to respond to different types of tumors, is based on simple gates used in electronics that will create a circuit only when two existing inputs are present.

The method is based on the fact that cancer cells differ from normal cells in the profile of their gene expression.

The researchers developed synthetic promoters – DNA sequences – designed to initiate gene expression, but only in cancer cells. The circuit is transferred to cells in the affected area via a virus, and focuses on tumors more accurately than existing treatments, as it requires two cancer-specific signs before it responds.

The researchers were able to build a system that works only in specific cancer cells. They attached an “alarm mechanism” to the system, which activates the immune system and infiltrates the system with virus vectors for a mouse with cancerous growths.

In response, only the cancer cells activated the alarm system that caused the immune system to attack the tumor. Moreover, the researchers have shown that the circuit can also focus on other types of cancer cells.

Therefore, the researchers hope the system will also be used to treat other diseases, such as rheumatoid arthritis, inflammatory bowel disease, and other autoimmune diseases.

Read the source article at Jpost

News

Cleveland Clinic researchers find link between bacterial imbalances and breast cancer

October 5, 2017, Cleveland: In a newly published study, Cleveland Clinic researchers have uncovered differences in the bacterial composition of breast tissue of healthy women vs. women with breast cancer. The research team has discovered for the first time that healthy breast tissue contains more of the bacterial species Methylobacterium, a finding which could offer a new perspective in the battle against breast cancer. Bacteria that live in the body, known as the microbiome, influence many diseases. Most research has been done on the “gut” microbiome, or bacteria in the digestive tract. Researchers have long suspected that a “microbiome” exists within breast tissue and plays a role in breast cancer but it has not yet been characterized. The research team has taken the first step toward understanding the composition of the bacteria in breast cancer by uncovering distinct microbial differences in healthy and cancerous breast tissue. “To my knowledge, this is the first study to examine both breast tissue and distant sites of the body for bacterial differences in breast cancer,” said co-senior author Charis Eng, M.D., Ph.D., chair of Cleveland Clinic’s Genomic Medicine Institute and director of the Center for Personalized Genetic Healthcare. “Our hope is to find a biomarker that would help us diagnose breast cancer quickly and easily. In our wildest dreams, we hope we can use microbiomics right before breast cancer forms and then prevent cancer with probiotics or antibiotics.” Published online in Oncotarget on Oct. 5, 2017, the study examined the tissues of 78 patients who underwent mastectomy for invasive carcinoma or elective cosmetic breast surgery. In addition, they examined oral rinse and urine to determine the bacterial composition of these distant sites in the body. In addition to the Methylobacterium finding, the team discovered that cancer patients’ urine samples had increased levels of gram-positive bacteria, including Staphylococcus and Actinomyces. Further studies are needed to determine the role these organisms may play in breast cancer. Co-senior author Stephen Grobymer, M.D., said, “If we can target specific pro-cancer bacteria, we may be able to make the environment less hospitable to cancer and enhance existing treatments. Larger studies are needed but this work is a solid first step in better understanding the significant role of bacterial imbalances in breast cancer.” Dr. Grobmyer is section head of Surgical Oncology and director of Breast Services at Cleveland Clinic. The study provides proof-of-principle evidence to support further research into the creation and utilization of loaded submicroscopic particles (nanoparticles), targeting these pro-cancer bacteria. Funded by a grant from the Center for Transformational Nanomedicine, Drs. Grobmyer and Eng are collaborating with investigators at Hebrew University to develop new treatments using nanotechnology to deliver antibiotics directly to the bacterial community in breast cancer. Breast cancer is the second most common cancer in women (after skin cancer) in the United States, where 1 in 8 women will develop the disease in their lifetimes. The study was funded by a Clinical Research Mentorship Award from the Doris Duke Charitable Foundation, The Society of Surgical Oncology Foundation, Cleveland Clinic’s Taussig Cancer Institute, Earlier.org, and Randy and Ken Kendrick. Dr. Eng holds the Sondra J. and Stephen R. Hardis Endowed Chair of Cancer Genomic Medicine at Cleveland Clinic. Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation’s best hospitals in its annual “America’s Best Hospitals” survey. Among Cleveland Clinic’s 51,000 employees are more than 3,500 full-time salaried physicians and researchers and 14,000 nurses, representing 140 medical specialties and subspecialties. Cleveland Clinic’s health system includes a 165-acre main campus near downtown Cleveland, 10 regional hospitals, more than 150 northern Ohio outpatient locations – including 18 full-service family health centers and three health and wellness centers – and locations in Weston, Fla.; Las Vegas, Nev.; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2016, there were 7.1 million outpatient visits, 161,674 hospital admissions and 207,610 surgical cases throughout Cleveland Clinic’s health system. Patients came for treatment from every state and 180 countries. Visit us at clevelandclinic.org. Follow us at twitter.com/ClevelandClinic. Editor’s Note: Cleveland Clinic News Service is available to provide broadcast-quality interviews and B-roll upon request. The Lerner Research Institute is home to Cleveland Clinic’s laboratory, translational and clinical research. Its mission is to promote human health by investigating in the laboratory and the clinic the causes of disease and discovering novel approaches to prevention and treatments; to train the next generation of biomedical researchers; and to foster productive collaborations with those providing clinical care. Lerner researchers publish more than 1,500 articles in peer-reviewed biomedical journals each year. Lerner’s total annual research expenditure was $260 million in 2016 (with $140 million in competitive federal funding, placing Lerner in the top five research institutes in the nation in federal grant funding). Approximately 1,500 people (including approximately 200 principal investigators, 240 research fellows, and about 150 graduate students) in 12 departments work in research programs focusing on heart and vascular, cancer, brain, eye, metabolic, musculoskeletal, inflammatory and fibrotic diseases. The Lerner has more than 700,000 square feet of lab, office and scientific core services space. Lerner faculty oversee the curriculum and teach students enrolled in the Cleveland Clinic Lerner College of Medicine (CCLCM) of Case Western Reserve University – training the next generation of physician-scientists. Institute faculty also participate in multiple doctoral programs, including the Molecular Medicine PhD Program, which integrates traditional graduate training with an emphasis on human diseases. The Lerner is a significant source of commercial property, generating 64 invention disclosures, 15 licenses, 121 patents, and one new spinoff company in 2016.

Read the source article at EurekAlert! Science News

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Hebrew University Faculty of Medicine gets Ben-Yehuda as first woman dean

For the first time since the Hebrew University of Jerusalem’s medical faculty was established in 1949, a woman has been named as its head. Prof. Dina Ben-Yehuda will be the second woman to head an Israeli medical school, after Prof. Rivka Carmi – now president of Ben-Gurion University of the Negev – was named dean of BGU’s Faculty of Health Sciences in 2000. Ben-Yehuda, director of hematology at the Hadassah University Medical Center, will take office as the 23rd dean of Hebrew University’s medical faculty on October 1. She will succeed Prof. David Lichtstein, who held the position for four years. A graduate of the BGU Health Sciences Faculty, Ben-Yehuda completed her internship in internal medicine and hematology at Hadassah and her research at the Center for Cancer Research at Memorial Sloan-Kettering Hospital in New York City. Upon her return to Israel in 1992, Ben-Yehuda established a lab for the diagnosis and research of malignant hematological diseases. A decade ago, she was appointed professor at the medical faculty and since 2002 has been running the hospital’s hematology department. She is involved in innovative research in the treatment of malignant cells using nanoparticles of a protein inhibitor in combination with extensive clinical work. The new dean is the mother of three girls and is married to Prof. Arie Ben-Yehuda, head of Hadassah’s Department of Internal Medicine. Dina Ben-Yehuda lost her oldest brother to cancer when he was seven years old. The family tragedy was a formative event that led to her decision to study medicine. During the Yom Kippur War, she coordinated the treatment of casualties for members of the Armored Corps and their families and was awarded the Chief of Staff’s Medal in 1967. “Our faculty is unique in that it trains medical professionals: researchers, pharmacists, specialists in public health, occupational therapists and nurses,” Ben-Yehuda said. “Only with the cooperation of all sectors, including students, can we train the next generation of medical professionals and give them the ability to understand the nature of the profession, while striving for knowledge, professionalism and respectful and ethical behavior in the process of medical treatment.”

Read the source article at Jpost

Spotlights

Dr. Ofra Benny

Dr. Ofra Benny was born and raised in Rishon Lezion. After her military service, she began her undergraduate studies in Biotechnology Engineering at the Technion. Upon completion of her engineering degree in 2001, Dr. Benny continued her education and earned a Ph.D. while working in the lab of Professor Marcelle Machluf. Her research focused on the development of polymeric drug delivery systems for the continuous release of inhibitors of blood vessel formation (anti-angiogenic factors) to treat glioblastoma brain tumors. She also developed an encapsulation procedure for peptides, specifically for PF4/CTF and PEX, in microspheres composed of the polymer PLGA. When injected intracranially in mice, these microspheres slowly release the peptides and inhibit vascular and tumor growth. Similarly, chemotherapy drugs released locally in the brain near the tumor site using this mechanism demonstrated improved anticancer activity with reduced systeic exposure. This research yielded a number of manuscripts in both the FASEB and Clinical Cancer Research Journals and, in 2006, she was awarded the Outstanding Pharmaceutical Paper Award by the Controlled Release Society for her work.

Upon completion of the Ph.D. at the end of 2006, Dr. Benny began her postdoctoral studies at Harvard University, Boston Children’s Hospital in Boston, Massachusetts under the mentorship of Dr. Judah Folkman—a pioneer of the angiogenesis field who demonstrated the dependency of tumors on the formation of new blood vessels. Dr. Benny focused her research on improving a broad spectrum anti-angiogenic drug, named TNP 470, by reengineering the drug for cancer treatment. Her challenge was to maintain the drug’s activity while improving its pharmacological properties and eliminating the neurological side effects found during clinical trials. Dr. Benny chose to covalently conjugate the drug to a di-block polymer mPEG-PLA. Selecting the length and properties of the polymer enabled its self-assembly into nanomicelles in an aqueous environment. Compared to the original drug, the new formulation of TNP -470, named Lodamin (from the Hebrew “no blood in”), showed better stability, solubility and absorption in the intestine. Additionally, Lodamin’s penetration of the brain was prevented and the consequent neurological side effects attributed to the original drug were eliminated, as demonstrated in mice. Lodamin was able to inhibit various cancers including skin, lung, brain, liver, breast, ovarian and pancreatic cancers. Because the nanomicelles accumulated in the liver after oral administration, a dramatic inhibition of liver metastasis was seen in the mice. The results were published in Nature Biotechnology in 2008, in a paper that described the development of the drug and its anticancer activity.
 
After the sudden death of Dr. Folkman, Ofra continued her research in the laboratory of Dr. Robert D’Amato. Her focus expanded to the vascular eye disease AMD (Age- related Macular Degeneration), one of the leading causes of blindness among elderly populations. Advanced stages of the disease are characterized by an accumulation of blood vessels in the retina (located at the back of the eye), which causes a rise in intraocular pressure and finally damage to the eye neurons. Ofra’s study demonstrated that Lodamin is highly active in the testing model of AMD (laser-induced choroidal neovascularisation) and exhibits advantages over the existing therapies by regressing neovascular lesions and not merely inhibiting their growth. Moreover, it can be administered in a less invasive manner, without intraocular injection as is required today.
In 2010, Dr. Benny was promoted to the position of Instructor at Harvard University and Associate Scientist at Boston Children’s Hospital. Her research continued to focus on the dynamic field of tumor microenvironment, cancer and ocular vascular diseases. She joined the journal Frontiers in Bioscience as managing editor, and was a guest editor for the Journal of Ophthalmology, managing a special issue: Lymphatic and Blood Vessels in the Eye: Physiology, Health, and Disease.

Since the beginning of 2013, Dr. Benny has been a faculty member at Hebrew University’s Institute of Drug Research, Faculty of Medicine, School of Pharmacy. Her team is currently investigating the mechanisms involved in angiogenesis and factors causing resistance to anti-angiogenic therapies. Their goal is to understand the mechanisms responsible for drug resistance in order to develop innovative treatments with improved activity for prolonged treatment without tumor escape. Treatment optimization is being investigated at the molecular level by searching for new drug targets, and at the formulations level by developing nanoparticles with improved cancer-targeting abilities and enhanced uptake.

Additional studies focus on understanding the tissue microenvironment in neovascular pathologies, including the lymphatic system. By better understanding this specific niche, Dr. Benny and her team will be able to develop innovative tools to deliver drugs more efficiently. To achieve these goals, the lab employs several different techniques, including drug encapsulation, polymer conjugation, molecular biology, tissue culture, cellular models of angiogenesis, vascular permeability, and cancer. The studies are performed in primary cultures of endothelial, lymphatic, and various cancer cell lines. In addition, the laboratory uses research models for angiogenesis, cancer, and metastasis.
News

The Lautenberg Center For Immunology and Cancer Research

The Lautenberg Center, headed by Professor Ofer Mandelboim, has achieved international recognition as a major unit for research and instruction in immunological science. Its personnel includes more than 30 faculty members, postdoctoral and research associates. Organized into several independent, but closely collaborating research units, the center’s staff, is pursuing a multifaceted program of investigation in tumor immunology, transplantation immunology, and basic cellular and molecular immunology. More than 1000 scientific communications – articles reporting research findings, reviews, chapters in textbooks and in symposium publications, books, and abstracts of lectures presented at international scientific conventions – have been published by investigators conducting their studies in the center’s laboratories.

The center offers formal courses of lecture and laboratory instruction in immunology, molecular biology, tumor biology and host-parasite relationship studies to medical, dentistry, and pharmacy students, and to undergraduate and graduate students in the natural sciences. Large numbers of graduate and medical students, including many from abroad, pursue dissertational research at the center, and foreign scholars with advanced standing are frequent visitors for prolonged periods of joint investigational endeavors.

A variety of clinical services and consultation to hospitals in Israel is provided, especially through its affiliated Unit of Tissue typing. The Lautenberg Center is linked to Israel and international scientific and medical communities by an intensive, ongoing program of collaborative basic studies and by its active role in the planning and carrying out of clinical trials pertaining to the diagnosis and therapy of neoplastic, infectious and parasitic diseases.

Spotlights

Dr. Zvika Granot

Investigating the progression of breast cancer and neutrophils

Dr. Zvika Granot, a senior lecturer, investigates breast cancer and its metastasis. A developmental biologist and award-winning scientist, he focuses on the role of neutrophils: white blood cells that help to fight infection. His laboratory recently discovered that healthy cells surrounding a tumor may be critically involved in the progression of cancer.

Dr. Granot co-led an important study that works with model tumors and human blood samples. His findings have challenged the concept that mature neutrophils have limited ability to change and adapt new characteristics. Dr. Granot discovered that while some neutrophils have anti-tumor properties, others promote tumor progression. In the early stages of cancer, tumor-limiting neutrophils prevail. However, as cancer progresses, the tumor-promoting neutrophil subpopulation outcompetes the tumor-limiting neutrophil subpopulation, leading to disease metastasis. Dr. Granot has received prestigious research grants, including from the Israel Cancer Research Fund. The Hebrew University Ph.D. conducted his postdoctoral training at Memorial Sloan-Kettering Cancer Center in New York.

Spotlights

Dr. Nataly Kravchenko-Balasha

Personalizing cancer therapies

Every person’s cancer grows in its own way and is unique in terms of the therapies to which it responds. Thus, there is a pressing need for personalized cancer therapies. Dr. Nataly Kravchenko-Balasha’s laboratory at the Hebrew University Faculty of Dental Medicine is analyzing the molecular variations between tumors. By studying inter-tumor heterogeneity, her goal is to help develop tumor-specific smart drug cocktails for fighting cancer.

Dr. Kravchenko-Balasha moved to Israel from the former Soviet Union at the age of 16; she spent four years as a postdoctoral fellow at Caltech but has always felt that Israel is her home. She remarks, “And the same is true for the Hebrew University, which is not only home, but is also among the best universities in the world, with world-class scientists working together.”

News

BioCanCell Announces Appointment of Ms. Ruti Alon to Board of Directors

JERUSALEM, Aug. 14, 2017 (GLOBE NEWSWIRE) — BioCanCell Ltd. (TASE:BICL), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel therapies to treat cancer, announced today the appointment of Ms. Ruti Alon to its Board of Directors. Frank Haluska, M.D, Ph.D., BioCanCell’s President and Chief Executive Officer, commented, “We are extremely pleased to welcome Ruti to BioCanCell’s Board of Directors. Ruti’s background and experience are an excellent fit as we prepare to launch two pivotal clinical trials of our lead investigational agent, BC-819, either of which may lead to registration in early stage bladder cancer. She has a distinguished record of leadership and accomplishment in finance and biotechnology, and she will bring her experience and insight to the strategic guidance of BioCanCell. The Board and the Company very much look forward to her joining us.” Ms. Alon is currently the founder and CEO of Medstrada. From 1997 to 2016, she served as a General Partner at Pitango Venture Capital, one of the most influential venture firms in Israel. Prior to her tenure at Pitango, Ms. Alon held senior positions with Montgomery Securities from 1981 to 1987, Genesis Securities, LLC from 1993 to 1995, and Kidder Peabody & Co. from 1987 to 1993, and managed her own independent consulting business in San Francisco in the medical devices industry from 1995 to 1996. Ms. Alon was the Founder and Chairperson of Israel Life Science Industry, a not-for-profit organization then representing the mutual goals of approximately 700 Israeli life science companies. She is also the Co-Founder of IATI, Israel Advanced Technology Industries, an umbrella organization to all high-tech and Life Sciences companies in Israel. Ms. Alon has a B.A. in Economics from the Hebrew University of Jerusalem, Israel, and an M.B.A. from Boston University. Ms. Alon commented, “I am truly excited to have the opportunity to join BioCancell’s Board of Directors. BC-819 has the potential to be the first of its kind DNA-directed cancer therapy. I look forward to being part of BioCanCell as it is targeting this serious unmet medical need.” Larry Howard, M.D., Chairman of the Board of Directors, added that “Ruti is a successful leader in the Israel biotechnology and life science industry. We will value her perspective and experience as she joins the leadership of BioCanCell.“ Ms. Alon’s appointment has been approved by BioCanCell’s Board of Directors. It will be finalized upon its ratification by a general meeting of shareholders in early September. About BioCanCell BioCanCell is a clinical-stage biopharmaceutical company focused on the discovery and development of novel therapies to treat cancer. The Company’s most advanced product candidate, BC-819, is in development as a treatment for early stage, non-muscle-invasive bladder cancer (NMIBC). Two registrational clinical trials of BC-819 are planned to be initiated in 2017: a single arm trial in patients whose disease is unresponsive to standard therapy, and a randomized trial, under a special protocol assessment (SPA) from the FDA, in patients who have failed a first course of treatment. For additional information please go to www.biocancell.com. Forward Looking Statements This press release contains “forward-looking statements” that are subject to risks and uncertainties. These forward-looking statements include information about possible or assumed future results of clinical trials, the anticipated effects of receiving Fast Track designation, the anticipated timeframe for conducting additional clinical trials and making regulatory submissions, and other strategic and business plans and objectives. These forward-looking statements are based on information BioCanCell has when those statements are made or its management’s good faith belief as of that time with respect to future events, and are subject to risks and uncertainties that could cause actual performance or results to differ materially from those expressed in or suggested by the forward-looking statements. These risks and uncertainties include, but are not limited to: the success of the approach to discover and develop prospective therapeutic products, which is new and may never lead to marketable products; a lack of history of commercial sales; a dependence on the success of BC-819, the development of which will require significant additional clinical testing before regulatory approval can be sought and commercial sales launched; a need to raise substantial additional funds to complete R&D activities; an ability to overcome scientific or technological difficulties that may be encountered and that may impede R&D activities; and an ability to obtain and maintain intellectual property protection for product candidates, including pursuant to licensed patents.

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News

First ‘Haploid’ Human Stem Cells Could Revolutionize Medical Research

Potential for regenerative medicine and cancer research earns doctoral student Ido Sagi a Kaye Innovation Award

June 28, 2017 — Stem cell research holds huge potential for medicine and human health. In particular, human embryonic stem cells (ESCs), with their ability to turn into any cell in the human body, are essential to the future prevention and treatment of disease.

One set or two? Diploid versus haploid cells
Most of the cells in our body are diploid, which means they carry two sets of chromosomes — one from each parent. Until now, scientists have only succeeded in creating haploid embryonic stem cells — which contain a single set of chromosomes. However, scientists have long sought to isolate and replicate these haploid ESCs in humans, which would allow them to work with one set of human chromosomes as opposed to a mixture from both parents.

This milestone was finally reached when Ido Sagi, working as a Ph.D. student at the Hebrew University of Jerusalem’s Azrieli Center for Stem Cells and Genetic Research, led research that yielded the first successful isolation and maintenance of haploid embryonic stem cells in humans. Unlike in mice, these haploid stem cells were able to differentiate into many other cell types, such as brain, heart, and pancreas cells, while retaining a single set of chromosomes.

With Professor Nissim Benvenisty, Director of the Azrieli Center, Sagi showed that this new human stem cell type will play an important role in human genetic and medical research. It will aid our understanding of human development – for example, why we reproduce sexually instead of from a single parent. It will make genetic screening easier and more precise, by allowing the examination of single sets of chromosomes. Additionally, it is already enabling the study of resistance to chemotherapy drugs, with implications for cancer therapy.

Diagnostic kits for personalized medicine

Based on this research, Yissum, the Technology Transfer arm of the Hebrew University, launched the company New Stem, which is developing a diagnostic kit for predicting resistance to chemotherapy treatments. By amassing a broad library of human pluripotent stem cells with different mutations and genetic makeups, NewStem plans to develop diagnostic kits for personalized medication and future therapeutic and reproductive products.

2017 Kaye Innovation Award
In recognition of his work, Ido Sagi was awarded the Kaye Innovation Award for 2017.

The Kaye Innovation Awards at the Hebrew University of Jerusalem have been awarded annually since 1994. Isaac Kaye of England, a prominent industrialist in the pharmaceutical industry, established the awards to encourage faculty, staff, and students of the Hebrew University to develop innovative methods and inventions with good commercial potential, which will benefit the university and society.

Ido Sagi received B.S summa cum laude in Life Sciences from the Hebrew University and currently pursuing a Ph.D. at the laboratory of Professor Nissim Benvenisty at the university’s Department of Genetics in the Alexander Silberman Institute of Life Sciences. He is a fellow of the Adams Fellowship of the Israel Academy of Sciences and Humanities and has recently received the Rappaport Prize for Excellence in Biomedical Research. Sagi’s research focuses on studying genetic and epigenetic phenomena in human pluripotent stem cells, and his work has been published in leading scientific journals, including NatureNature Genetics, and Cell Stem Cell.

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