According to our January 2008 Special Topic on
migraine research over the past decade, Jes
Olesen’s work ranks at #7, with 59 original
articles and review papers cited a total of 1,333 times
to date. InEssential Science
Scientific, Dr. Olesen’s record
includes 178 papers, the majority of which are
classified in the field of Neuroscience &
Behavior, cited a total of 3,069 times from January
1, 1997 to December 31, 2007.
Dr. Olesen is a professor at the University of Copenhagen as well as
the chief of the Danish Headache Center, headquartered in the Department of
Neurology at Glostrup University Hospital in Copenhagen. He is also a
member (and past president) of the International Headache Society, the
European Federation of Neurological Sciences, and the European Brain
Council, as well as a fellow of the Royal College of Physicians.
In the interview below, Dr. Olesen talks
with ScienceWatch.com correspondent Gary Taubes
about his migraine research.
What prompted the line of research on calcitonin gene-related
peptide that led to your highly cited 2004 New England Journal of
Medicine article (Olesen J, et al., "Calcitonin gene-related
peptide receptor antagonist BIBN4096BS for the acute treatment of
migraine," 350: 1104-10, 11 March 2004)?
We had done a lot of work on a particular signaling molecule, called CGRP,
which stands for calcitonin gene-related peptide. It’s found in
nerves that surround the brain blood vessels—the arteries of the
brain—and it is a very strong opener of the arteries; it widens the
arteries in the brain. We had shown that when you actually give this
substance to migraine patients, you can induce a migraine attack. That work
was published in the late 1990s, originally in Cephalalgia. That
result suggested that CGRP plays a very important role in migraine, and if
we could somehow block the effect of that molecule, we might have a new
kind of treatment for the disorder.
This particular New England Journal of Medicine article was
reporting on a clinical trial studying a compound that had been developed
by Bohringer Ingleheim in Germany. The compound proved to work and so was a
proof of principle: here was a potentially whole new class of drugs that
could now be developed, because blocking this particular receptor works in
migraine. After the trial, Merck developed a better compound that is now in
phase III trials.
Can you quantify for us how well the Bohringer Ingleheim
compound did in the trial?
a subjective phenomenon and that
makes it extremely difficult to
This was a phase II study, a proof-of-concept study, which means we had
relatively small numbers. So we were able to say it works, that it looks
pretty good, but we couldn’t say, for instance, how it worked
compared with other treatments. Roughly, it looked about the same as the
common drugs for migraines, called triptans. There are a lot of additional
issues that have to be worked out in further trials. This particular
compound was never going to go anywhere because you have to give it by
intravenous injection. That’s unsuitable for a drug but suitable for
a trial to prove the principle. The Merck compound can be given orally, as
a tablet, and so that’s what we’re now studying.
What have you been working on since that 2004
Our main focus is on repeating the success we had with CGRP. That means
looking at other messenger or signaling molecules, seeing whether they can
induce a headache in normal volunteers and a migraine in migraine
sufferers, and then finding out whether these compounds work in animal
experiments, with the hope of generating more targets for migraine drugs.
Have you found any?
Yes. We have found some, and they are going to be published. I think this
is the way to find new drugs for migraine.
Is that the exclusive focus of your lab at the
There’s one other molecule we’ve been working on, which we
haven’t discussed—nitric oxide. It can also induce a migraine
attack. If you inhibit the production of this molecule in the human body
you have a treatment for migraine attacks. We showed that quite a few years
ago and since then we’ve been studying how this molecule can possibly
be involved in migraine.
Do you know what it does to bring on the
That’s not completely clear, which means the explanation is a
complicated one. What nitric oxide certainly does is open up blood vessels,
the arteries of the brain. It may also have some interaction with CGRP.
These two seem to be interrelated in a number of ways. It’s also
involved in central pain mechanisms—in our sensitivity to pain, how
we perceive pain.
The papers you list as significant on your website have
very little overlap with ESI’s assessment of your most-cited
papers. You seem more concerned with genetic determinants of migraine
types. Why is that?
We have done a lot in genetics, but we’ve not had a great success
finding new genes. That’s a common phenomenon in this field. Genetic
research on migraines seems to be on the down slope. People were
enthusiastic about genetics a number of years ago but now it doesn’t
look like it’s going to tell us much about migraine or headache,
apparently because these are very complex disorders.
What’s the most difficult or challenging aspect of
The most challenging aspect of this work is that we don’t have any
clear biological markers. We cannot take a blood test and make a migraine
diagnosis from it, or score the severity of the migraine, and so on.
Migraine is a subjective phenomenon and that makes it extremely difficult
What do you see the next five years bringing in migraine
research and therapy?
Much more knowledge about the molecular mechanisms of migraine; several new
drug targets and one or two new drugs on the market that work by a totally
If you had an unlimited source of funding—if this
were an ideal world—what experiment would you do that you
couldn’t do now?
Actually, I would just do a lot more of the research that we are doing
right now. I’d also make sure that all our discoveries would be
translated into drug development, which is not happening at the moment.
Companies don’t seem to appreciate the importance of what we do.
Because it’s new. Companies always like to do more of the same.
Is there one message you would give to the lay public
about your research?
The final message is that investing both from a public and a private
perspective in migraine research is probably one of most profitable and yet
under-resourced areas you can find. We have data showing that. We have a
recent publication showing that migraine has the poorest resource support
of any major brain disorder.
Why do you think that’s the case?
Because there is no biomarker; there are no structural lesions. And
it’s mostly a female disorder—80 or 90 percent of the burden of
migraine is on women.
Does that funding situation cross national
If anything, it’s even worse in the United States than it is in
Jes Olesen, M.D.
Danish Headache Center
University of Copenhagen
Olesen's most-cited paper with 138 cites