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Nonagenarian Israeli scientist is still innovating

  • Published in Health


Nobody else was figuring out a way to better diagnose deadly ‘superbugs,’ so Nathan Citri did it himself


By Avigayil Kadesh
From his easy chair in a Jerusalem assisted living residence, Prof. Nathan Citri wondered why the desperate call of the World Health Organization for a way to contain antibiotic-resistant bacteria remained unanswered, and hospitals continued to be hotbeds for these deadly “superbugs.”
The 91-year-old Hebrew University microbiologist formally retired in 1989 but never stopped searching for solutions to urgent problems in medical diagnostics. He and his late wife and collaborator were especially focused on advances to benefit the world’s neediest populations.
In his home and university labs, they’d developed a prototype for bedside kits that detect and identify resistant bacteria from blood or urine samples, yielding lifesaving information within minutes. The standard lab technique, developed more than a century ago, takes precious days.

“Up until six months ago I was still confident that somebody would come up with this -- to me, obvious -- idea, but nobody did,” Citri says.
Realizing it was up to him, in September 2011 he took his iPad to London to show his idea to a world expert in the field, as well as the consistent results from a prototype produced at a British lab to which he’d emailed instructions.
Duly impressed, the expert gave Citri contacts at two British companies with the technology to produce this kind of kit. Both sent representatives the very next day to Citri's hotel. The first one to arrive got the contract, administered through Hebrew University’s tech transfer company, Yissum.
The lucky rep “was excited beyond belief,” says Citri. “There have been countless attempts at solutions, and my idea was so simple and straightforward.”
Though he’s no technophobe, he always urged his students at Hebrew and Harvard universities to see that simpler things leave less room for error.
“If I become aware of a problem that I feel like addressing, I try to simplify it to the extent that I can try my hand at it,” says Citri, who earned his PhD from Hebrew University of Jerusalem in 1954 and was academic vice dean of its medical school from 1982 to 1988.
‘This country saved my life’
Born Natan Cytrynowski in Lodz, Poland, in 1921, he was raised by ardent Zionist parents who spoke to their children in Hebrew – then a newly revived spoken language.
His fluency in Hebrew eased his absorption into pre-state Israel at 15, and earned him the chairmanship of the committee tasked with translating life-sciences lingo for the Hebrew Language Academy. Later he also coined new terms, three of which appear in a new booklet celebrating the Academy’s centennial with one outstanding example from each decade: milkshake (k’tzif chalav), microorganism (yetzoron) and blackout (chishachon).
Letters written in Hebrew are the only keepsakes he has from his parents and sister, all murdered by the Nazis.
On his own, Citri arrived in Palestine’s Ben Shemen agricultural youth village in 1937 through Youth Aliyah, a rescue organization established by Hadassah founder Henrietta Szold. Fittingly, today he lives on Szold Street not far from Hadassah University Medical Center.
“This country saved my life,” says Citri.
Lacking a high school diploma, with encouragement from the Jewish Agency he sat for exams to gain acceptance to Hebrew University, after volunteering in the British Army from 1942 to 1946. He studied bacteriology.
“When I was about 10, a book called Microbe Hunters was translated into Polish and I read it. They became the heroes of my childhood,” says Citri. “But I never planned to be a microbiologist. I intended to become a pioneer. However, after the army there was a call … for people to replace the lost Jewish intelligentsia, since so many had perished in Europe. I felt it applied to me. My parents were intellectuals and could have contributed so much. They were murdered at such an early age, and my sister wasn’t even 19.”
Taking time off to fight in the 1948 War of Independence, he earned his doctorate and did research fellowships at the National Institute for Medical Research in London and at the University of Illinois.
The love of his life
Citri married and fathered Miki, now a social worker in the Hadassah Medical Center; and Yoav, a scientist whose promising potential was cut short by a fatal accident in 1995.
He and his wife separated when the children were preteens. He met Naomi Zyk, a PhD from Montreal’s McGill University, when she was hired as his lab assistant during a stint at Harvard in 1962. For the next 50 years, until her death in 2011, she shared his life and worked by his side virtually 24/7.
In fact, the devoted couple started developing the resistant-bacteria ID kits together. “She didn’t live to see it become a reality, but she knew it would,” says Citri.
However, he says their best collaboration was their son Amichai, 38. A neurobiologist, he is finishing a post-doc at Stanford and will join the Hebrew University in August with a double appointment: at the Silverman Institute of Life Sciences and at the Safra Center for Brain Sciences. His proud father encouraged him to take the offer rather than remain in the United States.
“I can assure you that if I’d been offered positions abroad, I wouldn’t have hesitated to choose Hebrew University,” Citri relates. “I grew up without a country and my parents dreamed of settling here and had no way to get here. This is a country where, whatever you are lucky to contribute to, there is a good chance that you will live to see it make a difference. There is no other place like Israel.”


Safer radiation therapy

  • Published in Health


An Israeli company's biodegradable 'balloon' radically reduces the negative side effects of radiation in cancer treatment.



By Desmond Bentley
The main drawback of radiation therapy for cancer patients is that it harms healthy tissues surrounding a malignant tumor under radiation bombardment.
Now the Israeli company BioProtect has come up with a unique biodegradable "balloon" that physically separates cancerous and healthy tissues during radiation therapy for prostate cancer.
BioProtect's CEO, Amir Shiner, says the company's trademarked ProSpace represents a breakthrough in its field. "We're bringing a new product to the market," he says. "There's a clear clinical need for this product in view of the support by numerous publications for escalating radiation doses to prostate cancer patients undergoing radiation therapy. It makes the therapy far more effective."
In a multi-center, international study involving 26 prostate cancer patients, ProSpace was shown to significantly reduce the radiation reaching the rectal wall and consequent associated complications. It therefore allows for radiation at high doses without ill effects, meaning more efficient treatments with fewer treatment sessions at lower cost.
How does it work?
Made from biodegradable polymers, which have a proven safety record, the ProSpace device is filled with saline and implanted using the minimally invasive, well-established technique of transperineal insertion commonly used at outpatient centers.
The balloon remains inflated throughout the radiation therapy treatment. It then dissolves and reabsorbs into the body within three to six months, eliminating the need for removal. Patients involved in the trial reported that they felt no discomfort or pain from the implanted balloon, aside from mild and temporary discomfort at the access area at the perineum.
Because radiation therapy is a well-established, effective and widely accepted form of treatment for many types of cancer, it is expected that the BioProtect device can be used to implement safer and more effective radiation therapies for a variety of cancers.
"There's a strong need to have such a protection device," says Shiner, noting that BioProtect is not alone in this market. "There is one company that provides a gel product that is injected for the same need. Competition is always good - the feedback we've received from physicians is that they far prefer our product. It has a clear advantage in that it is reproducible. Due to its reproducible shape and size, and well-defined boundaries under a CT scan, it helps the doctor to administer the treatment effectively."
Europe first
In October 2010, ProSpace received the CE Mark, ensuring that it conforms to European regulatory requirements. BioProtect is now establishing a marketing network in Europe. "In April we started in Italy, and have now signed distribution agreements in five European countries," reports Shiner. "We're in the middle of a soft-launch process in those countries, and are negotiating to expand further in Europe, where we already have initial sales."
Last July, the ProSpace device received Israeli Health Ministry approval for marketing. In January, the company will launch a study utilizing its balloon for an innovative radiation therapy protocol at several medical centers in Israel.
In the United States, the company has already carried out a pilot study for the Food and Drug Administration and is now discussing with the FDA further clinical requirements to obtain clearance, says Shiner.
"We're a small company, based in Kfar Saba. Our R&D team and manufacturing are on site, while we are strongly focused on clinical activities, marketing and sales," he adds.
The company has already raised funds from three groups of investors: Xenia Venture Capital, which operates the technological incubator in Kiryat Gat where the company began as a startup; Virginia Life Science Investments, which invests in several Israeli healthcare companies; and the JumpStart NJ Angel Network. "We also have other private investors," notes Shiner. "Currently, we're working on more significant fundraising to take us to the next stage."


A cancer vaccine you can live with

  • Published in Health


Vaxil's groundbreaking therapeutic vaccine, developed in Israel, could keep about 90 percent of cancers from coming back


As the world's population lives longer than ever, if we don't succumb to heart disease, strokes or accidents, it is more likely that cancer will get us one way or another. Cancer is tough to fight, as the body learns how to outsmart medical approaches that often kill normal cells while targeting the malignant ones.
In a breakthrough development, the Israeli company Vaxil BioTherapeutics has formulated a therapeutic cancer vaccine, now in clinical trials at Hadassah University Medical Center in Jerusalem. If all goes well, the vaccine could be available about six years down the road, to administer on a regular basis not only to help treat cancer but in order to keep the disease from recurring.
The vaccine is being tested against a type of blood cancer called multiple myeloma. If the substance works as hoped - and it looks like all arrows are pointing that way - its platform technology VaxHit could be applied to 90 percent of all known cancers, including prostate and breast cancer, solid and non-solid tumors.
"In cancer, the body knows something is not quite right but the immune system doesn't know how to protect itself against the tumor like it does against an infection or virus. This is because cancer cells are the body's own cells gone wrong," says Julian Levy, the company's CFO. "Coupled with that, a cancer patient has a depressed immune system, caused both by the illness and by the treatment."
The trick is to activate a compromised immune system to mobilize against the threat.

A vaccine that works like a drug
A traditional vaccine helps the body's immune system fend off foreign invaders such as bacteria or viruses, and is administered to people who have not yet had the ailment. Therapeutic vaccines, like the one Vaxil has developed, are given to sick people, and work more like a drug.
Vaxil's lead product, ImMucin, activates the immune system by "training" T-cells - the immune cells that protect the body by searching out and destroying cells that display a specific molecule (or marker) called MUC1. MUC1 is typically found only on cancer cells and not on healthy cells. The T-cells don't attack any cells without MUC1, meaning there are no side effects unlike traditional cancer treatments. More than 90% of different cancers have MUC1 on their cells, which indicates the potential for this vaccine.
"It's a really big thing," says Levy, a biotechnology entrepreneur who was formerly CEO for Biokine Therapeutics. "If you give chemo, apart from the really nasty side effects, what often happens is that cancer becomes immune [to it]. The tumor likes to mutate and develops an ability to hide from the treatment. Our vaccines are also designed to overcome that problem."
For cancers in an advanced stage, treatments like chemo or surgery to remove a large tumor will still be needed, but if the cancer can be brought down to scale, the body is then able to deal with it, Levy explains. ImMucin is foreseen as a long-term strategy - a shot every few months, with no side effects - to stop the cancer from reoccurring after initial treatments, by ensuring that the patient's own immune system keeps it under control.
In parallel, the company is also working on a vaccine that treats tuberculosis, a disease that's increasing worldwide, including in the developed world, and for which the current vaccine is often ineffective and treatment is problematic.
Based in Ness Ziona, Vaxil was founded in 2006 by Dr. Lior Carmon, a biotechnology entrepreneur with a doctorate in immunology from the Weizmann Institute of Science in Rehovot. In June, Vaxil signed a memorandum of understanding to merge its activities into Sheldonco, a company traded on the Tel Aviv Stock Exchange.


US Approves 1st New Lupus Drug in 50 Years

  • Published in Health


Lupus Drug - First medication ever developed specifically for the autoimmune disorder


Vidushi Sinha, Washington, D.C.
The first new drug to treat lupus in a half century - and the first ever specifically developed to treat the autoimmune disorder - is heading to market in the United States. Under the trade name Benlysta, it is the first federally-approved drug to be derived from genomics, the study of genes and their functions.
Eva Gaskin has been married for 17 years. But one day four years ago, she suddenly was unable to recognize her husband, and became convinced that he had killed her family. Doctors said these strange mental episodes were symptoms of lupus cerebritis, which caused inflammation in her brain tissues.
"I had anxiety. I had insomnia," says Gaskin. "I had lots of things going on that we really did not understand and that was very frightening for my family until I got on the proper treatment, and those kinds of issues started to subside. But at first it was very scary.”
The brain inflammation that made Eva see her husband as a stranger and a killer soon moved to her lungs, and her breathing became painful. Lupus is a potentially fatal disease. It develops when the body's protector cells stop differentiating between healthy cells and bacteria. As a result, the immune system starts attacking its own body instead of protecting it from bacteria, viruses and parasites.
Until now, lupus sufferers have treated their varied symptoms - from mental disorders to skin rashes and painful joints - with a combination of drugs, including painkillers, steroids and anti-malarial medicines. Aside from being insufficient, these treatments have also carried the risk of toxicity.
But now, for the first time in 50 years, the U.S. Food and Drug Adminsitration has approved a new drug specifically to treat lupus.
“It’s so exciting to see that a drug is coming out that targeted specifically for lupus patients because in the past we have been taking drugs that have been found helpful but not specifically for us,” says Gaskin.
Benlysta also represents a medical milestone. Its American developer, Human Genome Sciences, calls it the first drug derived from the genetic mapping of human proteins.
Company vice-president Barry Labinger says the firm is proud of the fact that after so many years of research, development, and clinical trials, they finally have an anti-lupus drug that directly targets the autoimmune disorder.
“Benlysta works on the immune system by blocking a part of the immune system that becomes over-active in the presence of autoimmune disease," says Labinger. "Autoimmnue disease in particular tends to happen far more frequently in women and people of color and so Benlysta turns out to be an important drug for those patients, as well as a broader population for anybody who has lupus.”
Lupus affects women nine times more than it does men. And it occurs disproportionately in African-American, Hispanic and Asian populations.
Labinger says Benlysta is not a miracle drug, and it's not for everyone. “It is a very important step forward. There is room for more than one treatment for lupus patients over time and we hope that this is a first step towards a number of advances for patients with lupus.”
Human Genome Sciences will soon begin a large study of African-American lupus patients.
In the meantime, lupus sufferer Eva Gaskin says her condition is stable for now, but she's relieved she has Benlysta to fall back on if her lupus should flare up again.


Matches made in bone marrow banks

  • Published in Health


Both Jews and Arabs whose names are listed in their respective bone marrow registries are willing to donate to save the life of a perfect stranger.


By Avigayil Kadesh

Only about 1.2 million of the world's roughly 400 million ethnic Arabs live in Israel, yet the sole registry for Arab bone marrow donors is located in Jerusalem's Hadassah-Hebrew University Medical Center. Bone marrow transplanted from a genetically matching donor may be effective against blood cancers and a variety of genetic diseases.
Arab registry director Amal Bishara, an Arab woman with a Ph.D. in microbiology and immunology from Hadassah, has traveled to 60 Arab communities since the registry was created in 2008 as an offshoot of the hospital's 22-year-old Jewish registry. Through lectures, publicity campaigns, newspaper articles and social media, Bishara has brought in 9,000 registrants resulting in six donations.
But before she can collect samples - often with the help of her family or a cadre of retired Arab nurses - she must sell the concept of unrelated, anonymous donors. Since Arabs frequently marry relatives, at least 60 percent of patients find matches within their own extended families (on the flip side, about 90 percent of Arab requests for bone marrow transplants are for children with genetic diseases resulting from consanguineous marriages). Hadassah previously had little success in recruiting Arab registrants. Thanks to Bishara, attitudes are changing.
"A small [Arab] girl needed a transplant recently and our phone did not stop ringing," Bishara relates with obvious pride. "People want to participate. Now my emphasis is on getting university students to join because they are committed, young and healthy." Her overall goal is 50,000 registrants.
Get aware, get tested
About 15 million people are registered globally, says Dr. Shoshana Israel, head of Hadassah's bone marrow registry and tissue typing laboratory. "However, each ethnic population presents different tissue types, and you have to try to find a population most suitable for each patient," for example Druze and Bedouin Arabs or Georgian and Yemenite Jews. "Otherwise," continues Israel, "the chance of finding donors is very low. So we have to get people aware and tested."
Part of that awareness is accepting that the identity of the recipient is not revealed, and that an Arab might be a match for a Jew and vice versa. Anyone who balks at these conditions is not tested. As a result, few potential donors fail to follow through if they turn out to be a match.
"The donors are really angels," says Israel. "Even though it's not a huge operation, donating is not a trivial thing. Arabs and Jews alike are willing to go through the process just to save the life of someone they don't know."
Usually, the marrow stem cells are extracted from blood, rather than from bone marrow. After receiving injections to raise their stem cell count, donors are hooked up to an apheresis machine that harvests stem cells as the blood flows from one arm to the other. In cases where actual marrow is needed, it is extracted from a hipbone with a surgical syringe.
"We are very excited whenever we find a match," says Bishara, who was herself a backup donor for a 24-year-old female patient. "I often accompany donors through the whole process, and it actually changes their lives. One 19-year-old girl said it was the first time she felt she did something good in her life."
Cord blood bank in the works
Hadassah's was the first Israeli marrow registry, established by Prof. Chaim Brautbar and now including more than 75,000 potential donors. The non-profit Ezer Mizion registry, the largest Jewish bone marrow registry in the world, has about 500,000. Another small one is based at Sheba Medical Center near Tel Aviv.
"We are also working on the cord blood bank in parallel," says Israel. “If we don't find a donor from the marrow registry we might do better with cord blood, because it does not require a perfect match. That's a big advantage for minority populations like the Bedouins, where we don't have enough donors because we haven't had the budget to test them."
Hadassah and Sheba maintain public cord blood registries of samples banked by the organizations Magen David Adom and Dor Yeshorim.
In the past two years, Hadassah started using the simpler and less-invasive cheek swab method of acquiring tissue samples, rather than drawing blood. The fastest and most cost-effective way of processing the swabs is to send them to specialized labs in the United States. Even accounting for travel time, this procedure adds names to the registry as quickly as possible.
Funding is a chronic concern, and Brautbar spends much time soliciting overseas contributions - which can be earmarked for the Arab project if that is the desire of the funder. Israel and Bishara rarely have the budget for large testing drives. Instead, they reach out to specific patients' ethnic communities. But mass recruitment would allow for more and faster matching in Israel and other countries where transplants are done.
"When I explain that because of our unique genetics we only find matches for 10 percent of the Arab population without a family donor, that convinces people that we need them," Bishara relates. "It's a good experience and once people know it doesn't harm them they will be encouraged to join the registry and give a donation if they're matched."

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