Tag Archives: medicine.

Technion’s Nobel Laureates in Chemistry – Collect the Stamp!

Israel Post – International Year of Chemistry 2011

Technion Prof. Ehud Keinan, President of the Israel Chemical Society, had the vision to celebrate the international year of chemistry in a manner suited to the world-class position of Israel’s three Nobel Laureates in science. With determination and application, he engineered the release of official stamps celebrating the Year of Chemistry, and Israel’s Nobel Laureates.
Ubiquitin
Why our proteins must die so that we may live
Proteins are the machines that drive our bodies. They are responsible for all our activities, from the beating of our hearts, to walking, seeing, hearing, digestion, respiration and even the secretion of waste materials. Unlike useful items that surround us, like furniture and clothing, our bodies’ proteins are dynamic. They are constantly being destroyed and rebuilt, again and again. Our bodies destroy on a daily basis up to 10% of our proteins and generate new ones instead. This phenomenon raises interesting questions: why does this process occur at all, and how does it occur? Which diseases would happen if this mechanism was to fail? How can we cure such diseases? As part of the body’s quality control mechanism, proteins are destroyed after fulfilling their specific function in case they have been damaged by heat, by pollutants, by genetic mutation, or simply because they are no longer needed. Professors Aaron Ciechanover and Avram Hershko of the Technion – Israel Institute of Technology, and Irwin Rose of the University of California, Irvine, USA, were jointly awarded the 2004 Nobel Prize in Chemistry for discovering the mechanism that removes damaged or unnecessary proteins. These proteins are labeled for destruction by another small protein called ubiquitin, whose general structure is shown on the stamp. The structure was adopted from W. J. Cook and his coworkers, the Journal of Molecular Biology, 1987. Once tagged by this “kiss of death” the labeled proteins are removed by a biological shredding machine called the proteasome, while sparing healthy, untagged proteins. Aberrations in this protein destruction process may result in numerous sicknesses, including certain types of cancers and brain diseases. Many pharmaceutical companies are working to develop drugs to combat such diseases. One such drug to treat multiple myeloma, which is a form of blood cancer, is already used clinically.
Ribosome
Ribosome translates DNA code into life
Ribosome is the biological machine in every living cell that makes proteins from amino acids. Genetic information, which is stored in our DNA, is copied into RNA, which is then read by the ribosome and used to create proteins. This process is known as translation, meaning that the ribosome translates the genetic information from RNA into proteins, which in turn control the structure and function of all living organisms. The ribosome is a huge machine, consisting of three RNA chains and more than 50 different proteins. Understanding the ribosomal structure and its operating mechanism is critical for the scientific understanding of all kinds of life. In particular, this insight into the life of pathogenic bacteria opened the door to the use of ribosomes as an important target for new antibiotics. Many of today’s antibiotics cure various diseases by blocking the function of bacterial ribosomes. The 2009 Nobel Prize in Chemistry was awarded jointly to professors Ada E. Yonath of the Weizmann Institute of Science, Venkatraman Ramakrishnan of the Medical Research Council, Cambridge, UK, and Thomas A. Steitz of Yale University, USA. They showed what the ribosome looks like and how it functions at the atomic level. All three used a method called X-ray crystallography to map the position for each and every one of the hundreds of thousands of atoms that make up the ribosome. The image on the stamp, which is adopted from a paper published by Ada Yonath and her coworkers in 2001 in Nature magazine, shows a view into the tunnel of the large ribosomal subunit from which the newly constructed chain of amino acids exits. This huge structure shows the ribosomal proteins (shown in orange), the ribosomal RNA (blue and pink) together with the antibiotic erythromycin (red).
Ehud Keinan
Professor of Chemistry
Technion – Israel Institute of Technology,
President of the Israel Chemical Society,
Editor in Chief, Israel Journal of Chemistry,
Chairman of the Chemistry Committee,
Ministry of Education
 
Dr. Joerg Harms of the University of Hamburg is
acknowledged for the ribosome graphics.
Technical Details:
Issue: January 2011
Design: Haimi Kivkovitch
Stamp Size: 30 mm x 40 mm
Plate nos: 823 (two phosphor bars)
824 (two phosphor bars)
Sheet of 15 stamps, Tabs: 5
Printers: Joh. Enschede, The Netherlands
Method of printing: Offset

Making armor for the brain (The story of Moussa Youdim)

[Jerusalem Post: 11/13/2010]

Iranian-born Technion pharmacologist Moussa Youdim has worked for decades on drugs for Parkinson’s and Alzheimer’s disease and even ALS. Judy Siegel-Itzkovich interviews him.

  

PROF. MOUSSA YOUDIM and his wife Fruma. ‘The Nobel



His father’s struggle with deep depression over business troubles in 1957 changed the course of Moussa Youdim’s life, from studying in medical school to going into pharmacology and discovering a cure for that psychiatric disorder. Many patients with Parkinson’s and other diseases are grateful for that shift in the life of this 70-year-old Jew, who as a very active emeritus professor at the Technion-Israel Institute of Technology will next week share with seven others the $1 million EMET Prize for Art, Science and Culture.

The EMET Prize, awarded annually since 2002 for excellence in academic and professional achievements that have far-reaching influence, is sponsored by the A.M.N. Foundation for the Advancement of Science, Art and Culture in Israel, under the auspices of the prime minister. Youdim will receive his prize for brain science in the category of life sciences.

With a surname that comes from the Hebrew word yod’im (know) as his family for over 400 years in Persia were known for their intellectual pursuits, Youdim was given the name Moussa after an official in Teheran’s American Hospital who mistook her for Muslim and told his mother that she must call him Ali. When she protested that she was Jewish, he instructed her to name him Moussa. Since then, even though he is sometimes mistaken for being a Muslim (especially by airport security personnel), he has refused to change it to Moshe.

Warm, outgoing, polite and a man of the world, Youdim holds more than 100 international patents in neuropsychiatric drug development and cardiovascular drugs. He acts as a consultant for several major international pharmaceutical companies, and serves on many national and international scientific and grant-giving committees.

Not only have the contributions of the leading pharmacology researcher been included in many standard text books, but he has published a stupendous 800 scientific articles, edited 45 books, served on the editorial boards of 44 international scientific journals, lectured around the globe and received many national and international awards and several honorary doctorates – most recently the European College of Neuropsychopharmacology LifeTime Achievement Award and election to the Leopoldina Germany Academy of Sciences.

HE GOT used to traveling and managing on his own from a young age. Around his 12th birthday, he was sent to a boarding school in the English city of Brighton, and from there left for Canada to study medicine at McGill University – until his businessman father took sick – when there were no safe medications for depression, Youdim recalls in an interview with The Jerusalem Post. His father was given electroshock treatments in England and felt better, but he had recurrent attacks and was never the same.

Youdim’s mother became the family breadwinner.

In 1960, the only existing antidepressant medication, iproniazid, had been meant for treating tuberculosis, but it was found to make people who took it happier. Yet, it killed some people who took it along with cheese or wine, launching a race to find a safe antidepressant.

After taking courses in bio- and neuro-chemistry, he became enthralled with the idea of understanding how the brain works, and wondered how to fix it. Graduating with a BSc and MSc and then his doctoral degree in biochemistry at McGill’s Allan Memorial Psychiatry Institute, he returned to England for post-graduate work at the University of London and taught at Oxford and at the College de France in Paris.

YOUDIM RECALLED that nearly 40 years ago, he heard a lecture by Holocaust survivor Joseph Knoll about work on an antidepressant called deprenyl. Unfortunately, it wasn’t effective, but it also was not harmful to people who drank wine or ate cheese. A few years later, Youdim and Prof. Peter Reiderer of Austria thought and demonstrated that deprenyl was effective in treating Parkinson’s, the degenerative disorder of the central nervous system that impairs motor skills, cognitive processes and other functions, and whose symptoms include tremor, rigidity and unstable posture, along with cognitive and neurobehavioral problems, dementia and sensory and sleep difficulties.

Deprenyl, later named selegiline in the US, became the first monoamine oxidase B inhibitor for the treatment of Parkinson’s disease. But they found that deprenyl may indeed have side effects; Youdim searched for a deprenyl-like drug that would be more effective. He finally stumbled upon a candidate drug that was in his possession; he developed it into rasagiline (now patented as Azilect and sold by the Israeli company Teva Pharmaceuticals).

Margaret Thatcher’s anti-Socialist tenure as British prime minister annoyed Youdim and other scientists no end – “she was called a ‘milk snatcher’ when she took away free milk supplies for schoolchildren – and though he was happy at Oxford, he became alienated from England.

Simultaneously, Youdim visited Israel (although most of his family ended up in Los Angeles) and was invited to see the Technion’s new medical school, where the dean offered him a job to establish and head a pharmacology department; the only one in Israel then was at the Hebrew University in Jerusalem. “I liked Europe, but I thought Israel would be exciting – and indeed it has been.”

ALTHOUGH ACADEMIC pharmacology is necessary to build the pharmaceutical industry, Israel had few prominent people in the field, and the Weizmann Institute of Science in Rehovot never set up its own pharmacology department because it didn’t regard it as pure but rather applied science. It is ironical that many people at Weizmann now consider themselves drug developers, he adds.

Although he had received enticing offers from the US and Iran, Youdim agreed to come to Haifa to live in 1977. “I had to recruit people for the department and was asked to go to ulpan to learn Hebrew, but I taught in English; I didn’t have the time to learn Hebrew. I was given five years, but I still don’t really speak it,” he admits with some amusement.

He and his first wife had three children – Shai, Tal and Avigail, none of whom went into science – and they later divorced. On a blind date 15 years ago, he met Fruma, a high-school English teacher and mother of two whose Holocaust-survivor parents moved from Austria to Israel when she was two years old. Moussa and Fruma married a decade ago, and – speaking Hebrew like a native and feeling “totally Israeli” – she makes up for his lack of fluency in the language. When not flying around the world together, they live in a penthouse on a hill in Haifa that overlooks much of the city and the sea. After chairing the pharmacology department at the Technion’s Rappaport Faculty of Medicine until 1994, he went on to direct the Technion’s Eve Topf and US National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research and Teaching.

ALTHOUGH HE says he has has never regretted becoming an Israeli, Youdim encountered roadblocks in the bureaucracy and the academic establishment.

“It’s a small country, with one pie, and everybody wants a piece of it. If you didn’t grow up here, you may have difficulty. Politics is important and intertwined with other things.” But, he says, all this can be overcome, and his own success story proves it.

Two years after his arrival, he suggested to Teva – then a small generic medicine producer – that they offer a deal for rasagiline, but officials turned him down. But in 1987, as Teva was beginning to develop original drugs such as Copaxone for multiple sclerosis, Youdim got a call, this time to invite him to establish a unit to work on his Parkinson’s drug along with Technion colleague Prof. John Finberg.

Today, approved by the US Food and Drug Administration, it offers hope to millions of Parkinson’s patients (1.5 million Americans and four million Chinese alone). With annual sales worth $400 million and royalties earned by the Technion and the scientists, Azilect is now being marketed worldwide; it is considered the first neuroprotectivedisease modifying drug for Parkinson’s.

Azilect does not cure the disease, says Youdim, but it has been shown to slow the degenerative process in the brain and has been found in lab studies to actually improve damaged neurons. “The jury is still out. I have nothing to do with clinical studies, but all reports show it helps and has no more side effects than a placebo. There are patients who have been taking it for six or seven years and still benefit from it.”

There are also signs, he says, that a derivative of rasagiline named Cardiamit would help patients suffering from cardiovascular disease, and this is about 20 times more common than Parkinson’s; he has conducted research in this with Technion physiologist Prof. Ofer Binah. This drug is being developed at the Technion’s Alfred Mann Institute.

Asked about implants of electrodes in the brain to alleviate tremors, Youdim says those are not the solution for the large numbers of Parkinson’s patients. A drug is their only hope, as you can’t perform such operations on everyone, he adds.

Youdim has an even bigger target – Alzheimer’s disease. Working with Hebrew University pharmacology Prof. Marta Weinstock-Rosin and Teva, he has developed a new type of drug called Ladostigil (TV 3326), which is now entering Phase II clinical trials in Europe. It integrates rasagiline’s anti-Parkinson benefits with the anti-Alzheimer effects of Weinstock- Rosin’s drug rivastigmine. This is natural, he says, as many Parkinson’s patients also suffer from this dementia disease. The exclusive commercial rights for Ladostigil, which is already the first multi-functional anti-Alzheimer’s drug to reach clinical trials, have been granted to Avraham Pharmaceuticals by the technology transfer arms of the Technion and HU. If everything works out, he believes that Ladostigil will be his second original drug to be put on the market.

Youdim has established the importance of monoamine oxidase and brain iron metabolism for brain function that can lead to cognitive impairments and neurodegenerative diseases. Excessive iron produces oxygen free radicals, which cause degeneration and aging, including brain damage.

Alzheimer’s, he notes, is a very complex, multifactorial disease. “It is not purely neurological; there are probably also some psychiatric aspects, as many patients also have a predisposition to depression.”

More recently he has developed with Prof. Mati Fridkin of Weizmann Institute novel multifunctional iron chelators with monoamine oxidase and cholinesterase inhibitory activity for treatment of amyotrophic lateral sclerosis (ALS or Lou Gehrig disease, a form of which afflicts British theoretical physicist Prof. Stephen Hawking and many others around the world) as well as Lewy Body disease and Type 2 diabetes. “We’ve already published a paper on it, and are working on Huntington’s as well – the familial [genetic] degenerative neurological disease that is even more terrible. I work harder than ever before, even though officially I am retired.” He has been invited twice to Beit Hanassi to see President Shimon Peres, who has asked a group of Israeli neuroscientists to advise him on the establishment of a virtual neuroscience institute linking via Internet a number of research institutions that would collaborate on developing novel approaches to treat neuropsychiatric disorders and benefit the Israeli economy.

As for his native country of Persia, Youdim recalls that in 1978, when he was in Israel, the Shah of Iran invited him to Teheran, decorated Youdim on the monarch’s birthday and gave him a royal medal. “The Soviet Union fell, so fundamentalist Iran could as well. If I were one day invited back, I would visit. It’s a beautiful country.”

Youdim says he hasn’t even asked how much money his share of the EMET Prize will be, but “I don’t care about money; we have enough. I have received so many honors in Israel and abroad that a Nobel Prize is not my goal. There are so many brilliant scientists who have not become Nobel laureates. What is important to me are the many e-mails and phone calls I receive from grateful patients who have been helped by rasagiline. One example was a woman who called at 4 a.m. from Dallas to thank me because her husband had responded to the drug.”

But he will be excited and moved at the EMET Prize ceremony, he concludes. “I will surely think of my father and mother, who meant so much to me. They would certainly be proud.”