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in-cites,
June 2005
http://www.in-cites.com/papers/MihaelPolymeropoulos.html
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An
interview with:
Dr. Mihael Polymeropoulos |
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 r.
Mihael H. Polymeropoulos, CEO of Vanda Pharmaceuticals, Inc.,
of Rockville, Maryland, is a psychiatrist and molecular
geneticist who has done research on gene expression in
diseases such as Wolfram syndrome, Huntington’s disease,
Ellis-van Creveld syndrome, and breast cancer. Nine of his 20
most recent papers indexed in PubMed focus on genes related to
Parkinson’s disease, particularly mutation of the α-synuclein
gene. Here, he discusses his highly cited paper on this gene,
along with his previous and current research interests, with
in-cites correspondent Myrna Watanabe. A recent analysis of ISI
Essential Science Indicators
Web product for the last 10 years shows that the paper on
which Dr. Polymeropoulos was lead author (Polymeropoulos, M.H.,
et al., "Mutation in the α-synuclein gene identified
in families with Parkinson’s disease," Science
276:2045-7, 1997) ranks as the second most-cited paper in the
field of Neuroscience & Behavior, with 1,432 citations to
date. His full record in this field includes 18 papers cited
1,930 times to date. He also has 34 papers cited a total of
2,002 times to date in the field of Molecular Biology &
Genetics. When Dr. Polymeropoulos co-authored the 1997 Science
paper, he was in the Laboratory of Genetic Disease Research,
National Human Genome Research Institute of the National
Institutes of Health (NIH) in Bethesda, Maryland. He then took
a position as head of the Pharmacogenomics Department at
Novartis AG. He is one of the co-founders of Vanda
Pharmaceuticals, which was established in 2003 with financing
from Care Capital and Bio*One Capital of the Singapore
Economic Development Board. Dr. Polymeropoulos holds a medical
degree from the University of Patras in Greece, and is a
board-certified psychiatrist.
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In your opinion, why is your 1997 Science paper on the α-synuclein
gene in Parkinson’s disease so highly cited?
I had no idea that the paper was cited that highly. I knew that
it was cited; I was not aware of the impact. All of us in the
sciences want to do our research because of our own curiosity. At
the end of the day, we want to help patients. At least, when you see
an impact when it starts a new field of study, it’s very exciting.
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“That paper proved that genetic factors play a role in Parkinson's disease, and it set a new paradigm in Parkinson's disease.”
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Before that paper was published, there was not a conviction that
Parkinson’s disease had any genetic influence. That paper proved
that genetic factors play a role in Parkinson’s disease, and it
set a new paradigm in Parkinson’s disease. It pointed to a new
molecular mechanism that can, of itself, cause disease.
How did you become interested in studying the genetics of Parkinson’s
disease?
At the time, I was broadly interested in studying genetics of
simple and complex diseases and Parkinson’s was one of them. I was
mapping human disease genes and I mapped and cloned a number of
them. One of them was Wolfram syndrome, a rare disease with
diabetes, and Ellis-van Crevald syndrome—it’s a type of
dwarfism. Another was pycnodysostosis—that’s an interesting
dwarfism that is believed to be the disease that the painter
Toulouse-Lautrec had.
Have you continued your work on the genetics of Parkinson's disease?
If so, have you continued work on the synuclein gene or have you
looked at other genes?
Yes. Soon thereafter, we discovered a mutation in a gene
called UCHL1; that was actually a very significant paper. (Wintermeyer
P., et al., "Mutation analysis and association studies
of the UCHL1 gene in German Parkinson’s disease
patients," Neuroreport 11[10]:2079-82, 2000 and Zhang J,
et al., "Association between a polymorphism of ubiquitin
carboxy-terminal hydrolase L1 (UCH-L1) gene and sporadic
Parkinson’s disease," Parkinsonism Relat. Disord.
6[4]:195-7, 2000). In combination with synuclein, the mechanism of
producing Parkinson’s disease pathology was having abnormal
protein concentrations in the cell or difficulty in removing them. UCHL1
is a protein involved in garbage disposal in the cell; there’s a
defect in that.
What are you working on now? Why?
As the CEO of Vanda Pharmaceuticals, I’m working to apply
genetics and genomics in drug development. Now, I’m using the same
genetic and genomic tools to develop new treatments. For example, we
know a lot of drugs don’t work on everybody. My company is working
to customize drugs based on an individual’s genetic profile. One
of the drugs we are working on is for schizophrenia.
When you did the research for the 1997 paper, you were at the National
Human Genome Research Institute of the National Institutes of Health.
Were you working on similar research when you went to Novartis?
At Novartis, I established a global department for
pharmacogenetics, which involved itself in examining genetic factors
that influence drug response.
With the understanding of the power of genetics and genomics, but
also with the experience of drug development, it seemed that the time
was right to develop a new paradigm in drug development. We ask: What
can we use drugs for? What indications can we use small molecules for?
Who would benefit from the drugs? We do that by identifying genetic
markers that examine who are the patients that would have the best
efficacy and the best adverse effects profile, in whom the drug works
better with fewer side effects.
How did you end up as CEO of Vanda Pharmaceuticals? Was Vanda a
spin-off from Novartis?
No, it was not a spin-off. A number of people who were at
Novartis joined me. The initial funding was funding by Care Capital,
a venture firm in Princeton, New Jersey. One of the people there was
at Novartis. It was founded in the spring of 2003.
Your short biography says you were trained in Molecular Genetics and
Psychiatry. Could you explain this?
I studied medicine in Greece. I studied molecular genetics at the
National Cancer Institute. I’m board-certified in psychiatry. I
spent another 10 years or so at the NIH working on human genetics. I
also practiced psychiatry while I was at the NIH.
Mihael Polymeropoulos, M.D.
Vanda Pharmaceuticals
Rockville, MD, USA
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in-cites, June 2005
http://www.in-cites.com/papers/MihaelPolymeropoulos.html
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cites
