Professor Marta Weinstock-Rosin has always been used to live on the wrong side on the fence: in Austria she was ‘too Jewish’, in the British Academy of the fifties she was ‘too much of a woman’, in Israel she appeared to be ‘too British’ and for Novartis she seemed ‘too Israeli’…
/ By Gali Weinreb, Globes Online /
It only takes a minute to know Prof. Marta Weinstock-Rosin, the ‘mother’ of the Exelon drug, used to treat symptoms of Alzheimer disease when you ask to take her picture. She raises her hand and reaches her thumb towards her nose. This gesture is her British manner of telling us: “bite me”. Marta Weinstock-Rosin knows perfectly well that she needs nobody’s permission and she makes sure that everyone knows that. In fact, she has never bothered to get a confirmation for being herself, and there were times that it might have been useful.
A message from above
The discovery happened in the early eighties. Weinstock-Rosin has been investigating morphine’s suppression of the breathing process , one of the biggest problems in its use as a pain killer medication.
“I found that morphine reduces the release of brainstem substance called acetylcholine, making the brain less sensitive to carbon dioxide -” she says. Therefore, she developed, regardless of Alzheimer’s, a substance that prevents the breakdown of acetylcholine in the brain stem.
One of the first materials that she examined seemed highly effective and also durable, but unfortunately, as she thought at that point, had no impact upon the amount of choline in the brain stem, only the front of the brain.
A minute before she completely gave up on that molecule, Weinstock-Rosin went to the library and found by accident a copy of “Science” magazine. “I’ve always been fascinated about science”, she explains, “and suddenly, or maybe it was a message from heaven, I read that Alzheimer’s is characterized by a deficiency of acetylcholine in the hippocampus and frontal brain, and whose absence is somewhat related to cognitive impairment. I remember standing there, without someone to talk to, but I rushed to the lab and I said to myself: ”I must make a change in direction. ”
Weinstock-Rosin believes that this amazing coincidence, or maybe a miracle, was the reason for her current research at the Hebrew University in Jerusalem.
You are not one of us!
She was born In Vienna, Austria, and after her father was arrested for being Jewish, the family has decided to flee to England in 1939. As soon as they arrived, her father was taken into custody again, because he was a citizen of an enemy state. Her mother was forced to wander in England without income, without language and without a profession, and look for something to eat for the children.
“In that time”, tells Weinstock-Rosin, “I learned whatever was necessary about coping with emotional stress. My mother went down to the shelter with us every night and never showed fear. We thought it was great to go down to the shelters, we were singing and laughing. When I saw what was happening on 1991, (G.W the gulf war) how mothers are putting their children to stress, I said no wonder everyone in Israel a little basket case”.
She attributes ‘Coolness’ not only her mother, but the general atmosphere in the UK. “One day we left the shelter and saw that half of the houses on our street were destroyed. Two women came with us have found that have no home at all. Then one of them said to another: ‘Do not worry, we’ll have a cup of tea’, which replied in a calm voice:” Yes Mary, but Where? ‘, and then my mother said:’ These Brits are going to win the war. ”
World war 2 was finally over, but little Marta had some battles ahead of her. “I was a very naughty girl at school, she admits, “But I also was very curious. I had to fight the system until they let me study science. The girls school had no suitable program and the teachers were not good enough, so I attended physics classes at the boys class. When I applied for medical school, my father feared that I will never find a husband”.
As opposed to her papa’s concerns, Marta got married and later got pregnant but kept on working. “It was not accustomed in Britain of the sixties, neglecting your children in order to go out to work. I was a three times strange: an Orthodox Jewish woman. There were just a few Jews at the department. I assume that some of the Ph.D students concealed their religion. I have never thought of doing so, and I never thought to hide it, and I had more publications than anyone, so they had to respect me. At age 24 I already had an article in ‘Nature’ magazine, and I was pregnant at the time.
However, when the time arrived to move ahead and become a senior lecturer, the department’s manager explained to her that: “You are not one of us. You are not eating with us and you never make it to Christmas Parties”. At that moment she decided to fulfill her husband’s dream and move to Israel: “When I came back to my director and told him I was leaving, he told me: “After all that we had done for you…”. I replied: “What have you done for me. I did everything on my own…”.
Marta , her husband and their three little kids immigrated to Israel in the late sixties. “At first I was not happy at all”, she remembers. It was hot and humid, and I could not stand the pushing in the bus, but my husband told me to stop standing in line like a British woman, or we will have to walk” The family finally settled in Israel. Her husband, geriatrician Professor Arnold Rosin got a position in a Hospital in Rechovot, while Weinstock-Rosin started to work in The Tel Aviv University. Later she moved to the Hebrew University.
Were you were satisfied with the Academy’s attitude towards you?
“Look, I prefer clear rules, so everyone knows for sure what he does or does not deserved. This is the British part remained and in Israel it is not always the situation. In my opinion it does not add Israel worldwide respect. We must behave openly and honestly.
But England is not perfect either. I prefer a thousand times bending the rules here on the types of fraud and about cliques sophisticated of England. In both countries being a woman, religious and not knowing the language is not a hit, but here with a little good will I can get along, and in England it iis not enough” .
“Teva had zero experience”
Weinstock-Rosin’s discovery occurred at a time of applied academic esearch boom, resultant awakening of the university administration realized the economic potential of the field.
“Before that time, should I tried to convince other researchers to hooker
I would not receive a response more difficult.” After all, ‘we Hebrew University, the flagship of the basic science’, . they told me so at the School of Pharmacy. Now is called the Institute of medicine, and there One does not want to develop drugs. ”
At the same time in the major pharmaceutical companies were very open purchase of patents from universities, even without clinical feasibility. Today they usually prefer to purchase the drugs at a later stage, often the inventions just could not get up there, due to lack of funding.
When Exelon was found, the situation was different, but life was not simple at all.” I wrote the pharmaceutical patent on my own, without the assistance of patent editors. It was registered in 1985, only in Israel. The research’s funding was only a $100, 000, but led to the Ministry of Science decision to primary check the drug’s commercial potential through an Israeli pharmaceutical company, or in other words: Teva, which was the only Israeli pharmaceutical firm in that time.”
I presented the product to them and they took the time to examine it and in the mean time the patent clock was ticking. By the time they got back to us and informed us they are interested – I already knew that they won’t do it. They had zero experience in Alzheimer disease and they still don’t”.
We shell get back to the triangle of Weinstock-rosin, Teva and Alzheimer disease, but it is interesting to note that by that time she also started developing the Copaxone, Teva’s flagship drug until today. I wonder what would happen today the company has also had Exelon, sell for a billion dollars. After a while, Weinstock-Rosin was looking for another ‘bride’ “I spoke at a conference on Alzheimer’s in my development, and at the end of the lecture I realized it was now or never and I said, ‘Well guys, it’s for sale!”.
The hidden scientist
The agreement was signed shortly afterwards with Sendoz (today, a part of Novartis), that committed to bear all costs of product development and grant Weinstock -Rosin and the university fine royalties. However, reveals Weinstock-Rosin, “they made us not to tell that the drug has been invented in Israel”.
One can assume that the lady who always fought for the right thing did not like this clause, but she could bear this insult for the sake of science and medicine. For many years she could not take the credit for the drug, already considered to be groundbreaking. “The university wanted to grant me The “K” award for donation to mankind. I told them:” Have you forgotten? It is not an Israeli invention, and I did not get the award.”
Professor Weinstock-Rosin was deeply involved in the developing of the medication, even without the credit, and also wrote scientific articles in the field. Her name has been omitted. “They said it was due to the Arab boycott, but I suspect it was much more convenient to say that they invented the drug”.
Only in 1997, more than a decade after the agreement had been signed, Weinstock-Rosin was invited to the Novartis (that now owned Sandoz) conference. In the course of her lecture, she saw an own image on the screen, with the subtitle: “Marta Weinstock-Rosin, the mother of Exelon”. “Now it is allowed to tell” Novartis people told me, and all my friends and the Israeli and worldwide scientific community said: “WHAT, how come we did not know anything?”
After the drug was launched, she decided to receive large amounts, probably dozens of $ million. She invested part of the sum in scientific research, including her new founded company, ‘Avraham Pharmaceuticals Ltd’. and she also donates large amounts for philanthropy, but refuses to discuss it.
“I have 20 grandchildren, and all of them are financially taken care of. I’ve been telling myself, why wait till I get to heaven. My lifestyle has not changed. The only thing is that I pay the physiotherapist myself, without bothering about insurance issues”.
The next generation of Anti-Alzheimer medications
In the years that passed since the Exelon has been launched, Weinstock-Rosin has been working on a new drug, treating MCI – Alzheimer p Ltd.rimary cognitive disorder.
The new medication is being developed by Avraham Pharmaceuticals Ltd. Until today, the company raised more approximately $ 25 millon the ‘Yissum Research Development Company Ltd.’, the technology transfer arm of the Hebrew University of Jerusalem, ’ Pontifax’, ‘Clal Biotechnology Industries’ and the ‘Technion Research and Development Foundation Ltd.’ As said before, Weinstock-Rosin has also invested in the company herself. The company is run by Dr. Yona Gefen, , former director of product development BioLineRx. Chairman is Ya’acov Michlin, CEO of application.
The product was developed for treating both Alzheimer and MCI, but failed experiment with Alzheimer’s. The company continues to develop it to MCI because Professor Weinstock-Rosin believes that though these are different illnesses, the drug works on both through different mechanisms.
The product has also gone through Teva, but it forgot to bring it back to its founder… the drug is actually a chemical fusion inhibitor Atztin the same family choline Exelon and Azilect drug activity part of nature, developed by Prof. Moussa Youdim of the Technion, and listed and sold as a cure for Parkinson’s.
In order to develop the medication, Weinstock-Rosin and Youdim had to take an intellectual risk Azilect is a drug that inhibits an enzyme called MAOb and serves as a drug to treat early stages of Parkinson’s disease. In the human body are two types of MAO. MAOa inhibitors are effective drugs in treating depression, but not used due to serious side effects called “cheese effect” – MAOa used digestive enzymes dissolution as tyramine, found in various foods such as cheese. MAOa delay gastrointestinal causes tyramine reaches the blood and causes a rise in blood pressure and even stroke.
However, Weinstok – Rosin revealed that despite delays in Sldustigil MAOa and MAOb the brain is not keeping him in the digestive system and will not cause side effects as a result of an excess of tyramine. Small doses the drug do not delay or MAO acetylcholine esterase, but may be effective through its control of the immune system. “And hurry up already, ” says Weinstock-Rosin to the company’s CEO, Yona Gefen, “All my friends are asking when they will use the drug.”
The Exelon is sold today by Novartis in billion dollars a year. It is one of the few drugs on the market for the disease, improving patients memory and brings about 30% of patients for up to a year, slowing the progression of the disease for two years. Patent on the drug is supposed to expire in 2014.
A few years ago Weinstock-Rosin , accompanied by Professor Simon Benita, a Hebrew University colleague, traveled to Novartis headquarters in order to convince the company’s management to support the development delayed released Exelon. “Delayed release should lead to fewer side effects that cause symptoms because the drug enters the brain too quickly. Novartis had not accepted the argument, claiming that the side effects are nausea and vomiting, and it’s not about the brain? We proved the connection.” Now hope Rosin – Weinstock that Exelon patch delayed release will come into the market, give a few more decades of a patent, and will also generate revenues to Novartis, the Hebrew University Weinstock-Rosin, her physiotherapist and her grandchild . About 35 million people are about to suffer from Alzheimer’s by 2015, and the cost of treatment of the disease is expected to reac $ 19 billion – making it one of the world’s most expensive diseases.
For many years, he Alzheimer treating market leader was Pfizer’s Ariceptwhich, like Haklson, preventing the breakdown of Acetylcholine. Its patent expired in 2010 and currently some new drugs dominate the market – Rivastigmine, Galantamine (Reminyl) of Janssen and Memantine of Lundbeck and Forrest Laboratories.
Only this year two promising drugs failed clinical experiments, including a product of Pfizer and Jhonson & Jhonson, developed in the Tel Aviv University. Another Israeli attempt, made by ‘Allon Therapeutics Inc.’ failed to achieve the desired result.’
Since that early diagnosis is crucial for dealing with the disease, ‘Ely Lilly’ acquired the company ‘Avid Radiopharmaceuticals’ for a sum of $ 811 million. Avid developed a new imaging test amyloid beta. The test is also used as a tool for diagnosis and drug development process.
In Israel there are two more medical device companies, also engaged in Alzheimer research: Brainsway, which is at a stage of clinical trials, in order to examine the a short-term brain magnetic stimulation of the brain of long-term Alzheimer disease log term, and Neuronix, that deals with short-term brain stimulus the brain, but when the stimulus moves the patient’s cognitive training improves the condition, according to experiments conducted company. Weinstock – Rosin believes that a combination of unexaggerated body exercise, challenging brain activity and proper nutrition can slow the disease’s progression. “According to studies performed by my Geriatrician husband. Prof. Arnold Rosin, public awareness to the disease has already been slowing down Alzheimer progression without any treatment.”
– So, what should we eat?
The studies results are slightly contradictory. Vitamin C has an interesting course of action, but its presence in the body might reduce concentrations of other materials that act effectively on the target. Maybe blueberries. Maybe walnuts., truth is that we not really know yet.”