Yet another huge success in Israel’s scientific research – they have invented the medicine of completely curing cancer and this medicine will be available to patients from 2020. Another team of Israeli scientists already have found the scientific solutions for diabetic patients who currently are living on insulin injection, while another team has invented micro pancreata.
Isn’t it great news for cancer and diabetic patients around the world?
Certainly it is! These innovations will be beneficial to people around the world. Even our neighbors in South Asia, such as India and Nepal can also use these innovations in treating millions of people from cancer and diabetic. But, we in Bangladesh – cannot be benefited from it. No, it’s not unwillingness of the Jewish State in helping Bangladeshi cancer and diabetic patients from being cured. It is because of our policymaker’s anti-Semitic and anti-Israel mindset that stops us from having benefit of such scientific innovations. Bangladesh unfortunately considers Israel as an ‘enemy state’ simply because of appeasing Iran and those Palestinian terrorists. It should be mentioned here that, after our war of independence in 1971, Israel was amongst the first four nations to recognize Bangladesh, while Palestinians waited until 1973 in doing so.
According to a report published in the Jerusalem Post, a small team of Israeli scientists think they might have found the first complete cure for cancer.
“We believe we will offer in a year’s time a complete cure for cancer,” said Dan Aridor, of a new treatment being developed by his company, Accelerated Evolution Biotechnologies Ltd. (AEBi), which was founded in 2000 in the ITEK incubator in the Weizmann Science Park. AEBi developed the SoAP platform, which provides functional leads to very difficult targets.
“Our cancer cure will be effective from day one, will last a duration of a few weeks and will have no or minimal side-effects at a much lower cost than most other treatments on the market,” Aridor said. “Our solution will be both generic and personal.”
It sounds fantastical, especially considering that an estimated 18.1 million new cancer cases are diagnosed worldwide each year, according to reports by the International Agency for Research on Cancer. Further, every sixth death in the world is due to cancer, making it the second leading cause of death (second only to cardiovascular disease).
Aridor, chairman of the board of AEBi and CEO Dr. Ilan Morad, say their treatment, which they call MuTaTo (multi-target toxin) is essentially on the scale of a cancer antibiotic – a disruption technology of the highest order.
The potentially game-changing anti-cancer drug is based on SoAP technology, which belongs to the phage display group of technologies. It involves the introduction of DNA coding for a protein, such as an antibody, into a bacteriophage – a virus that infects bacteria. That protein is then displayed on the surface of the phage. Researchers can use these protein-displaying phages to screen for interactions with other proteins, DNA sequences and small molecules.
In 2018, a team of scientists won the Nobel Prize for their work on phage display in the directed evolution of new proteins – in particular, for the production of antibody therapeutics.
AEBi is doing something similar but with peptides, compounds of two or more amino acids linked in a chain. According to Morad, peptides have several advantages over antibodies, including that they are smaller, cheaper, and easier to produce and regulate.
When the company first started, Morad said, “We were doing what everyone else was doing, trying to discover individual novel peptides for specific cancers.” But shortly thereafter, Morad and his colleague, Dr. Hanan Itzhaki, decided they wanted to do something bigger.
To get started, Morad said they had to identify why other cancer-killing drugs and treatments don’t work or eventually fail. Then, they found a way to counter that effect.
For starters, most anti-cancer drugs attack a specific target on or in the cancer cell, he explained. Inhibiting the target usually affects a physiological pathway that promotes cancer. Mutations in the targets – or downstream in their physiological pathways – could make the targets not relevant to the cancer nature of the cell, and hence the drug attacking it is rendered ineffective.
In contrast, MuTaTo is using a combination of several cancer-targeting peptides for each cancer cell at the same time, combined with a strong peptide toxin that would kill cancer cells specifically. By using at least three targeting peptides on the same structure with a strong toxin, Morad said, “we made sure that the treatment will not be affected by mutations; cancer cells can mutate in such a way that targeted receptors are dropped by the cancer.”
“The probability of having multiple mutations that would modify all targeted receptors simultaneously decreases dramatically with the number of targets used,” Morad continued. “Instead of attacking receptors one at a time, we attack receptors three at a time – not even cancer can mutate three receptors at the same time.”
Furthermore, many cancer cells activate detoxification mechanisms when in stress from drugs. The cells pump out the drugs or modify them to be non-functional. But Morad said detoxification takes time. When the toxin is strong, it has a high probability of killing the cancer cell before detoxification occurs, which is what he is banking on.
Many cytotoxic anticancer treatments aim at fast-growing cells. But cancer stem cells are not fast growing, and they can escape these treatments. Then, when the treatment is over, they can generate cancer again.
“If it does not completely annihilate the cancer, the remaining cells can start to get mutations again, and then the cancer comes back, but this time it is drug resistant,” Morad said.
He explained that because cancer cells are born out of mutations that occur in cancer stem cells, most of the overexpressed proteins which are targeted on the cancer cell exist in the cancer stem cells. MuTaTo’s multiple-target attack ensures that they will be destroyed as well.
Finally, some cancer tumors erect shields which create access problems to large molecules, such as antibodies. MuTaTo acts like an octopus or a piece of spaghetti and can sneak into places where other large molecules cannot reach. Morad said the peptide parts of MuTaTo are very small (12 amino acids long) and lack a rigid structure.
“This should make the whole molecule non-immunogenic in most cases and would enable repeated administration of the drug,” he said.
Morad said their discovery could also reduce the sickening side-effects of most cancer treatments, which stem from drug treatments interacting with the wrong or additional targets, or the correct targets but on non-cancerous cells. He said MuTaTo’s having a combination of several highly specific cancer-targeting peptides on one scaffold for each type of cancer cell would increase the specificity to the cancer cell due to the avidity effect. In addition, in most cases, the non-cancer cells that have a protein in common with the cancer cells do not overexpress it.
“This makes a great difference between the two kinds of cells and should decrease the side effects dramatically,” Morad said.
He equated the concept of MuTaTo to the triple drug cocktail that has helped change AIDS from being an automatic death sentence to a chronic – but often manageable – disease.
Today, AIDS patients take protease inhibitors in combination with two other drugs called reverse transcriptase inhibitors. The drug combination disrupts HIV at different stages in its replication, restrains an enzyme crucial to an early stage of HIV duplication and holds back another enzyme that functions near the end of the HIV replication process.
“We used to give AIDS patients several drugs, but we would administer them one at a time,” Morad explained. “During the course of treatment, the virus mutated, and the AIDS started attacking again. Only when patients started using a cocktail, were they able to stop the disease.”
Now, he said, people with AIDS are HIV carriers, but they are not sick anymore.
The MuTaTo cancer treatment will eventually be personalized. Each patient will provide a piece of his biopsy to the lab, which would then analyze it to know which receptors are over-expressed. The individual would then be administered exactly the molecule cocktail needed to cure his disease.
However, unlike in the case of AIDS, where patients must take the cocktail throughout their lives, in the case of MuTaTo, the cells would be killed, and the patient could likely stop treatment after only a few weeks.
The company is now writing patents on specific peptides, which will be a large bank of targeting toxin peptides wholly owned and hard to break, said Aridor.
Morad said that so far, the company has concluded its first exploratory mice experiment, which inhibited human cancer cell growth and had no effect at all on healthy mice cells, in addition to several in-vitro trials. AEBi is on the cusp of beginning a round of clinical trials which could be completed within a few years and would make the treatment available in specific cases.
Aridor added: “Our results are consistent and repeatable.”
Israeli technology can also cure diabetic:
In 2017, during the MIXiii Biomed 2017 pharma startup competition, a young Israeli company that has cured type-1 diabetes in mice and was already hopeful of doing the same for humans won the first prize beating dozens of other firms.
They have explained how these mice were cured, exactly. According Prof Eduardo Mitrani from the Hebrew University of Jerusalem, the father of this breakthrough technology, and head of the scientific advisory board at Betalin Therapeutics,
Just how these mice were cured, exactly? “They were cured of advanced stages of severe diabetes,” explains Prof. Eduardo Mitrani from the Hebrew University of Jerusalem, the father of this hopefully breakthrough technology, and head of the scientific advisory board at Betalin Therapeutics, named “the most innovative biopharma company of the year” at Biomed.
The diabetes in question is type-1, which is an autoimmune disease that destroys the pancreas’ ability to secrete insulin, as well as severe cases of type-2. These conditions are chronic and need to be treated by insulin shots, for life.
Teams around the world are working on this not-uncommon disease, but the Israeli startup has a unique approach, says Mitrani, its scientific adviser.
Its secret is to treat diabetes not by aiming to transplant naked cells that secrete insulin, but by implanting, lab-built whole, albeit microscopic pancreata. “I think that, with some modesty, we’re the only one trying to recreate the whole organ,” Prof Eduardo Mitrani told the Haaretz.
Why create a whole micro-pancreas, with all the difficulty that entails, rather than just inject healthy naked pancreatic cells like everybody else?
Because that doesn’t work. Transplanted cells die quickly. “It turns out that we are not built of cells but of tissues and organs,” says Mitrani – A pancreatic cell does not and cannot operate in glorious isolation. It operates within the environment of the pancreas, which operates within the environment of the body, etc.
These micro-pancreases have been a great success in mice, as reported a year ago in PLOS ONE.
The testing technique for the technology involved chemically destroying the mice’s insulin-producing cells, then implanting the micro-pancreata into the newly hyperglycemic rodents. (Being self-contained units, the micro-organs can be implanted virtually anywhere in the body.)
If the mouse lives, the micro-pancreas is working – it’s controlling the animal’s glucose levels. If the mouse dies, it isn’t working.
“We found we could keep the mice functioning even for three months, the longest period tested,” says the professor, elaborating that without a working pancreas, we (and mice) cannot survive for more than a few days at most.
As a control for the experiment, they took mice that had survived all that for a month and removed the micro-pancreata, following which the animals died.
Ideally the team would have used pancreatic cells to create the micro-scaffolds on which they build their micro-organs, but they discovered that lung tissue worked better. For one thing, as Mitrani explained to Haaretz, 95% of the tissue in our pancreases is involved in producing digestive enzymes, not insulin regulation. For another, the lung tissue with its enormous surface area proved most compatible.
The engineered organs are made in the lab, and in contrast to say human ears grown on transgenic mice, these are microscopic.
Pressed on whether a microscopic micro-pancreas is enough to sustain a human, Mitrani explains simply: “You need a lot of them.” Then he turns enthusiastic. “In fact, that’s what make it so functional!” he told Haaretz. “Its very microscopic dimensions. By being so small, it doesn’t need vascularization. It functions through diffusion, and will function anywhere in the body.”
To elaborate the point: once implanted in the chemically-diabetic mice, the micro-pancreases do become vascularized, which means, they connect to our blood systems. That is, says Mitrani, simply what organs have evolved to do.
Theoretically, because it’s so small, the micro-pancreas can survive without connecting to our blood systems. But actually that’s how it monitors our blood glucose, and produces the correcting insulin.
When might this micro-pancreas technique be available for more than mice? Not for years, Mitrani confirms, and that’s assuming they can raise the money for clinical trials, always a problem for biotechnology startups. Once they have the financing, they need to do broader animal testing, then human testing, which would be done either in Canada or the United States.
“The most successful marriage in evolution is between cells and their supporting connective tissue. Nature has been looking at it for 500 million years,” says the professor. “We are unique because we are trying to preserve and reproduce this interaction.”
Another Israeli innovation for the diabetic patients:
If you are currently living on insulin injection, here is good news for you from an Israeli pharmaceutical company. Although diabetes is often associated with insulin injections, Jerusalem-based pharmaceutical company has developed an innovative oral insulin capsule that transforms injectable treatments into oral therapies. The capsules, for both types of diabetes, are in advanced Food and Drug Administration (FDA) clinical trials since 2016 and expected to be in the market from 2020.
Nadav Kidron, CEO and cofounder of Jerusalem-based Oramed Pharmaceuticals grew up in a home where diabetes was always part of the conversation. His mother, Miriam, worked for almost 20 years in the Diabetes Unit at Hadassah-Hebrew University
Together with Nobel Prize winner Prof. Avram Hershko, they developed a previously-unimaginable solution that enables proteins, such as insulin, to be delivered orally and intact into the liver – the organ that regulates the secretion of insulin into the bloodstream.
“Rather than treating excessive glucose in the blood, we shut off production from the source. This is a much more physiological way of treating diabetes. The vision is that the new paradigm of treating diabetics is by diet, exercise, oral insulin and, eventually, injectable insulin,” Kidron said.
ORAL ADMINISTRATION of current injection-only therapies for conditions including diabetes also offers clear benefits for patient lifestyles.
“There should be a world that will push back the point where patients are insulin-dependent, which is also far more expensive. The dream is to see smiling kids and adults because they can have a better lifestyle which can cost less, and both they and society will be much happier.”
In November 2015, Oramed signed licensing and investment agreements worth up to $50m. with Chinese investment and incubation company HTIT for exclusive rights to market the company’s insulin capsules in China, Hong Kong and Macau. Kidron anticipates that their product will be registered in China before the US.
“The East has been catching up with the West. There are 100 million diabetics in China, but the problem is that two-thirds are undiagnosed,” said Kidron. “Due to their adoption of a non-healthy lifestyle and due to the number of undiagnosed patients for now, there are huge fears over how they are going to treat diabetes.”
Oramed’s platform can take any protein otherwise injected and administer it orally instead. The company is currently working on other products including GLP-1 Analog, which causes people to lose weight and stimulates insulin production.
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