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
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.
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.
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
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
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.
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
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
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
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
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.”
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
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.”