Home inFocus Israel (Summer 2019) Israel’s Amazing Med-Tech Innovation Stream

Israel’s Amazing Med-Tech Innovation Stream

Abigail Klein Leichman, Brian Blum and Israel21c Spring 2019
A eosinophil white blood cell among red blood cells. (Illustration: Kateryna Kon/Shutterstock)

Nanosynex: Stopping the Superbug Surge

by Brian Blum

Almost 700,000 people around the world are estimated to die each year – not from the illness for which they went to the doctor or hospital – but from an infection resulting from contact with antibiotic-resistant bacteria.

In the United States alone, two million patients contract infections from superbugs; 23,000 people die from those infections. Goldman Sachs economist Jim O’Neill estimates that by the year 2050, more people will die from antibiotic-resistant bacterial infections than from cancer.

One of the ways superbugs develop is when a patient is prescribed the wrong antibiotics. The bacteria “learn” from that incorrect treatment and can share their newfound resistance with other bacteria. “The body becomes an incubator for resistant bacteria,” explains Diane Abensur Bessin, chief executive officer of Nanosynex, an Israeli startup working on a novel approach to help physicians avoid mis-prescribing antibiotics.

“If we give a patient the correct treatment at the right dose, then no resistance will be created, the patient will be cured faster, and other patients won’t be infected by resistant bacteria,” Abensur Bessin says.

Nanosynex’s solution is a diagnostic test that determines which bacteria in a patient’s body are resistant to which antibiotics – in just four hours. That compares favorably with the day or two or more required for traditional diagnostic tests. The result: physicians can more quickly prescribe the antibiotics that will work.

This will entail some change in behavior among doctors, who tend to prescribe a broad-based treatment rather than taking blood or urine samples and waiting for results. It’s not that physicians are in cahoots with the bad bacteria; their patients come in suffering and doctors want to provide fast relief. “But every minute counts when you’re dealing with resistant bacteria,” Abensur Bessin says. If you don’t get your test results back for a couple of days, it may already be too late to stop resistance from developing.

Antibiotic overprescribing is a particular problem in primary care, where it is viruses—not bacteria—that cause most infections. About 90 percent of all antibiotic prescriptions in the United States are issued by general practitioners.

Nanosynex is creating a kit that will be sold to laboratories; it contains disposable cards, a fluorescent reading device and software to do the analysis.

The technology is based on “microfluidic” features, requiring a smaller quantity of bacteria than other testing technologies, Abensur Bessin explains. The sample is mixed with a fluorescent dye; the intensity of the fluorescent signal is proportional to any bacterial growth.

Abensur Bessin came up with the idea for Nanosynex with co-founder Brazilian native Michelle Heyman, while both were studying for their MBAs at the Technion (Israel Institute of Technology). The two approached the university’s technology transfer office and asked which researchers had technologies that were mature enough to be turned into a company.

“We met with five different professors,” Abensur Bessin relates. “We wanted something that had a short time-to-market—five years or less.”

That’s how the two were introduced to Prof. Shulamit Levenberg, dean of the Technion’s biomedical-engineering faculty. Levenberg and her team had already been working for several years on the microfluidic “chip” that would become the basis of the Nanosynex kit.

Paris-born Abensur Bessin was particularly interested in identifying a medical technology around which to build a company. Her father has a firm in France that distributes diagnostic tools across Europe. With the marketing channels already in place, Levenberg’s invention was a match. “We knew there was a huge potential,” Abensur Bessin says. “There was no debate on the need to create this.”

Nanosynex incorporated in 2017 and has raised $1 million with another $500,000 pledged from the Israel Innovation Authority. The five-person company is operating out of the Technion’s in-house accelerator but will be moving to its own offices soon.

In 2018, Nanosynex was one of 10 companies accepted into IBM’s Tel Aviv-based accelerator for healthcare startups. The company receives blood for testing from Rambam Healthcare Campus in Haifa and Shaare Zedek Medical Center in Jerusalem. The head of Rambam’s microbiology department is on Nanosynex’s scientific advisory board.

Abensur Bessin says when Nanosynex results were compared with those from existing diagnostic devices, “they were exactly the same but done in half the time.”

Slowing the rise of the superbugs is just the start of what Abensur Bessin hopes will be a “long-lasting business that will grow internationally.”

In the meantime, if your doctor tells you to wait a few hours before he or she prescribes an antibiotic, don’t become too anxious: it will be for the good of your health — and the wellbeing of the entire planet.

Diagnoz.me: Smartphone into Diagnostics Microscope

by Abigail Klein Leichman

If your eye is oozing and red and you suspect you have an infection, you have to make an appointment with your doctor and get a lab analysis before you can start treatment with antibiotics. Physicist-turned-biologist Ariel Livne wondered if the whole process could be done at home by pairing some simple optics equipment with his smartphone to analyze biological samples – in the case of an eye infection, a teardrop.

That is the basis of the startup Diagnoz.me of Jerusalem, cofounded by Livne in November 2017 with Tamir Epstein, with the help of a pre-seed grant from the Israel Innovation Authority.

“Our innovation is that we enable the smartphone to see bacteria,” Livne says. “Once you see bacteria you can perform medical diagnostics. Our technology transforms a low-cost disposable together with a regular smartphone into a high-end medical diagnostics microscope.” 

Still in the proof-of-concept stage, Diagnoz.me aims to enable patients to run tests at home, receive lab-grade results within minutes and instantly share them with their physician.

“We have shown that our image-analysis software can detect bacteria as accurately as a high-end lab microscope that costs over $100,000,” says Livne.

The optics add-on would be a disposable chip device sold at a pharmacy for less than $20. You’d put the relevant biological liquid onto the chip, whether urine, saliva or a teardrop, “in a convenient way so it’s not disgusting or unhygienic. The camera takes and analyzes the pictures and sends you and your physician automatic results.”

Diagnoz.me is not the only Israeli company pioneering the home diagnostics sector.

TytoCare of Netanya and New York sells a home exam kit and app that lets people perform basic medical exams guided by a doctor. The device includes instruments to check ears, throat, heart and lungs, skin and body temperature and transmits those images and sounds to the physician.

Healthy.io of Tel Aviv, which recently raised $18 million in a Series B round, sells a smartphone-based home urinalysis kit and is starting a test-and-treat service in the UK for urinary-tract infections in collaboration with pharmacy chain Boots.

Livne explains that most home diagnostics developers are using PCR, a technology that identifies the DNA of specific bacteria.

Diagnoz.me uses a different technology, fluorescence microscopy, which has been around for over 100 years – but it wasn’t until about 2017 that smartphones had the right high-level specs to make Diagnoz.me possible. “The physician receives the same kind of information as from a lab, including bacterial count, to know what you have. If you need a prescription, that can be done electronically as well,” says Livne.

The founders won a 3 million Euro prize at the Health 2018 Summit held in Rishon LeZion.

Livne and Epstein have decided that Diagnoz.me’s first use-case will be vaginal infections, the most common gynecological problem, accounting for more than 10 million office visits per year in the United States.

“We looked at a number of different infections and vaginal infections stood out because they are very common but unfortunately most women don’t go for treatment because it’s so unpleasant,” Livne explains.

“Possibly 80 percent of women do anything to avoid going to the gynecologist so they try over-the-counter and home remedies instead. But they are in pain and it lowers their quality of life. We can help these women because collecting the sample and running the test is very easy and done in private.”

The technology can be adapted to detect each type of relevant bacteria, in this case those that cause vaginal infections.

Diagnoz.me is now raising seed funding. Livne estimates it will take about two to three years for the product to reach the market. Meanwhile, Livne and Epstein are seeking strategic partnerships and continuing to develop the product with a medical advisory board including, among others, the former head of the Women’s Health Department at the Lin Center in Haifa, and an obstetrician/gynecologist who heads Femicare VZW in Belgium.

Eosinophils: Cells related to allergies and asthma may destroy cancer

by Israel21c Staff

surprising new study from Israel finds that malignant colorectal cancer cells can be eliminated with eosinophils—white blood cells that originate in bone marrow and may once have killed off intestinal parasites, but which today are responsible for chronic asthma and allergies.

The research, published in Cancer Immunology Research this year, was led by Prof. Ariel Munitz of the Tel Aviv University Sackler School of Medicine department of microbiology and clinical immunology and conducted by his doctoral student Hadar Reichman, in collaboration with colleagues in Tel Aviv Medical Center’s gastroenterology department. “Eosinophils are white blood cells that secrete powerfully destructive proteins,” Munitz said. “They may have played an evolutionary role in combating parasites. But now that most people, particularly in the West, enjoy good hygiene and few parasites, the eosinophils have become destructive agents, causing allergies and asthma.

“Our new research theorized that since eosinophils are capable of killing parasites and can cause damage in the lungs of asthma patients, they might play a role in cancer treatment and would be able to kill tumor cells.”

The largest eosinophil reservoir is situated in the digestive system, so the researchers initially decided to test their theories on colorectal cancer. In the first stage of research, they selected samples from tumors of 275 patients to determine the number of eosinophils in a tumor as compared with the stage and severity of the disease.

“We found that the higher the number of eosinophils in the tumor, the less severe the disease, which represents a clear correlation,” said Munitz. “We identified that the cancerous environment attracts these cells, which infiltrate the tumors and flourish there for a long time.”

The researchers subsequently tested their hypotheses in various mouse models of colorectal cancer. They discovered that eosinophils displayed potent anti-tumor activities and could directly kill tumor cells.

“We also found that when eosinophils were activated by a protein called IFN-gamma, they induced an even greater tumor-killing response,” Munitz explained. “Following various extensive analyses, we concluded that eosinophils have unique and distinct activities in comparison with other cells present in the tumor. For example, eosinophils can kill tumors independently of known tumor-fighting cytotoxic T cells.”

He believes eosinophils could be used in treating cancer if their robust anti-tumor response somehow could be unleashed pharmaceutically, or by combining treatments to harness the potent forces of both eosinophils and cytotoxic T cells.

“We have discovered a new target for immunotherapy for cancer patients — the eosinophils,” concluded Munitz. “We hope that our research will serve as a foundation for drug development in a number of different approaches.”

The study was supported by the Israel Cancer Research Foundation, the Israel Cancer Association and the Israel Science Foundation.

Brian Blum is a journalist and high-tech entrepreneur at ISRAEL21c. Abigail Klein Leichman is a writer and associate editor at ISRAEL21c.