(MENAFN- AzerNews)
The renowned European neurologist residing in Denmark, Mesud
Ashina, is an active member of the Azerbaijani diaspora. As the
President of the International Headache Society and a professor of
neurology at the University of Copenhagen, Mesud Ashina has been
awarded the medal of the Republic of Azerbaijan "For Merit in
Diaspora Activities." By a decree from the head of state on
December 8, 2020, Mesud Ashina was elected to the Board of Trustees
of the "Yaşat" Foundation.
On the initiative of the State Committee on Work with the
Diaspora and the "Yaşat" Foundation, this European neurologist
provides free neurological care to veterans who fought for
territorial integrity and to the families of martyrs, while also
actively participating in a number of other projects. Today, the
prestigious medical journal New England Journal of Medicine
published an article on a new method for treating migraines. This
event is significant not only due to the development of a new drug
for a condition long considered incurable, but also because the
author of the article and head of the study is our compatriot,
Danish-Azerbaijani neurologist Professor Mesud Ashina, one of the
world's leading specialists in this field.
Currently, Professor Ashina holds the position of professor of
neurology at the University of Copenhagen and senior consultant in
neurology at Copenhagen University Hospital – Rigshospitalet. As of
2024, he is recognized as one of the world's foremost experts on
headache disorders, according to the Expertscape ranking. Mesud
Ashina received his medical degree from Azerbaijan Medical
University in 1988. He later completed his PhD and M. at the
University of Copenhagen and completed his neurology residency at
Rigshospitalet.
We interviewed Professor Ashina to discuss his discovery,
research, and the future prospects for migraine treatment.
Professor, could you elaborate on migraines? They are
often perceived as just severe headaches, but in reality, they are
a far more serious condition. Could you dispel some myths,
especially regarding the idea that they are incurable?
Migraine is not simply a severe headache, as many believe. It is
one of the most common and underestimated conditions, affecting
around one billion people worldwide, or roughly one in seven.
Migraine is a chronic neurological disorder that, besides headache,
includes symptoms such as nausea, vomiting, photophobia, and
phonophobia. Attacks can last for several days, and any movement or
sound can intensify the pain to an unbearable level.
It's important to note that about 20% of those suffering from
migraines experience attacks at least twice a week. This means that
nearly 200 million people live with this condition regularly,
losing dozens of days each year to debilitating attacks.
Migraine significantly reduces work capacity and social
activity. In terms of "years lived with disability," it ranks as
the leading neurological disorder. It is a serious chronic
condition that requires a thorough approach to treatment.
Professor, how has the science of migraine evolved, and
how do modern medications influence its treatment? What new
challenges do patients and doctors face in managing this
condition?
Migraine has a unique neurobiology that dictates its course.
Over the past 30 years, science has made significant strides in
treating it. In the early 1990s, drugs specifically designed to
stop migraine attacks were introduced. These medications target
migraines only, without affecting other types of pain, which was an
important breakthrough.
However, a new problem emerged: frequent use of these
medications can lead to a paradoxical headache. This condition is
called "medication-overuse headache" - a headache caused by the
overuse of medications. Therefore, these drugs are effective for
people with infrequent attacks, but when migraines are frequent,
improper use can worsen the condition.
Given recent advances in drug development, can we say
that migraines can now be effectively prevented? What preventive
methods are most effective today, and are they suitable for all
patients?
Yes, migraine prevention has become possible, though in the past
it wasn't specific. Medications developed for other conditions,
such as hypertension and epilepsy, were used to reduce the
frequency of attacks, but they often had side effects and weren't
always effective.
With the advent of new drugs targeting the CGRP molecule,
migraine prevention has become more precise. These drugs can reduce
the number of migraine days for 40% of patients, cutting the
frequency of attacks by 50% or more. However, they do not produce
significant improvement for everyone, indicating that further
development is needed to help a wider range of patients.
Thus, despite progress, migraine prevention is not effective for
all, and new solutions need to be developed.
Could you please tell us about your own research on
migraines? What is the focus of your work, and what prospects does
it open for understanding the mechanisms of this
condition?
My group has been researching migraines since 2006, focusing on
molecules that play a key role in its development. We aim to
identify molecules involved in triggering attacks to deepen our
understanding of migraine mechanisms. Our research is conducted
directly on people and examines molecules acting on nerves around
the brain's blood vessels, as well as on nerves responsible for
pain conduction.
My hypothesis is that certain molecules can provoke migraine
attacks in patients. This research could help develop new
therapeutic approaches that block these processes, improving the
quality of migraine treatment.
You mentioned that in your research, you induce migraine
attacks in patients. Could you explain how this works and how this
method is unique compared to other studies on neurological
disorders?
Yes, the ability to induce migraine attacks in controlled
conditions is a crucial part of our research. Migraine differs from
other neurological disorders in that its attacks are episodic-they
come and go. This allows us to study migraine in its active phase,
which is not possible with chronic conditions like Parkinson's
disease or dementia, where symptoms are always present.
The uniqueness of my approach lies in inducing migraine attacks
in patients to observe their development and study the biological
mechanisms in real time. It's similar to a situation where a person
knows that wine might trigger a migraine but decides to drink it
anyway. Patients in our studies understand the possibility of an
attack, but they also know they are under medical supervision and
will receive help if necessary.
We use certain molecules to provoke migraine attacks. In people
without migraines, these molecules may cause only a mild,
short-term headache, but in those who suffer from migraines, they
trigger a full-blown attack. This allows us to better understand
how migraines develop at the molecular level and aids in the
development of new targeted treatments.
Thus, our method offers a unique opportunity to study migraines
in the active phase, opening new avenues for effective therapeutic
solutions.
Could you explain the role of molecules in the
development of migraines, and how your experiments have advanced
understanding of their impact on the disease's
pathogenesis?
One of the key molecules involved in the development of
migraines is PACAP (Pituitary Adenylate Cyclase-Activating
Polypeptide). This molecule is present in structures associated
with migraines, such as the perivascular nerves that innervate
brain vessels and regulate their response to stimuli. During the
activation of these nerves, mediators like PACAP are released,
which can trigger migraine attacks.
In 2009, my lab conducted a study in which PACAP was
administered intravenously to patients over a 20-minute period. The
study included two sessions: one with PACAP and the other with a
placebo. In more than 50% of patients, PACAP induced migraine
attacks, confirming its significance in the pathogenesis of the
disorder.
These findings led to the hypothesis that blocking PACAP or its
receptors could become a new method of treating migraines. This
study laid the groundwork for further developments in targeted
therapy, aimed at blocking molecules involved in the onset of
migraines, and opened up the possibility of creating more effective
and precise medications.
*How do the approaches to migraine treatment using small
molecules differ from those using monoclonal antibodies? What are
the advantages and disadvantages of each method, and how do they
influence the choice of treatment strategy?*
Small molecules and monoclonal antibodies have different
approaches to treating migraines. Small molecules, such as receptor
antagonists, block the receptors responsible for migraine
development, providing a short-term effect (6-12 hours). They are
convenient to take, as they are available in tablet form. The
downside is that they need to be taken frequently.
Monoclonal antibodies block the same receptors but provide a
longer-lasting effect, which can last for weeks or months. However,
they require injections, as they are broken down in the
gastrointestinal tract when taken orally.
The choice between small molecules and antibodies depends on the
need for quick symptom relief or long-term prevention, as well as
patient preferences and the ease of administration.
Could you tell us about new approaches to treating
migraines with antibodies, and how your collaboration with Lundbeck
contributes to the development of these methods? What stages of
research have been proposed to test their
effectiveness?
New approaches to treating migraines include the development of
antibodies against molecules like PACAP. One of these methods
involves creating monoclonal antibodies that block PACAP itself,
preventing it from interacting with receptors and thus neutralizing
its effect. This approach is different from traditional ones as it
works at an earlier stage of the pathological process, eliminating
the action of the molecule that triggers the migraine.
Lundbeck developed an antibody targeting PACAP and approached me
for collaboration, knowing about my research and interest in this
hypothesis. Together, we proposed conducting a study to evaluate
the effectiveness of this antibody in patients with migraines. This
approach to treatment could represent a significant breakthrough,
as it allows for direct targeting of a key molecule involved in
migraine pathogenesis.
I suggested conducting additional studies on healthy individuals
before moving on to clinical trials with migraine patients. Studies
on healthy volunteers (Phase 1) help to test the drug's tolerance,
identify side effects, and determine the optimal dose. My idea was
to test the blocking effect of the antibody by administering PACAP
intravenously to volunteers and simultaneously assessing the
antibody's ability to prevent the physiological reactions caused by
PACAP. This study will help better understand the effectiveness of
the new method and pave the way for the next phase of clinical
trials in migraine patients.
What physiological reactions were you expecting to
see?
We expected reactions such as vasodilation, facial flushing, a
drop in blood pressure, and an increased heart rate-typical effects
of PACAP. If the drug could block these reactions in healthy
individuals, it would increase the likelihood of its effectiveness
against migraines.
The study showed that the antibody against PACAP successfully
inhibited vasodilation, reduced heart rate, and diminished
headaches. This confirmed the potential of the antibody as a
treatment for migraines and other PACAP-related disorders. After
this, I led Phase 2 trials, sponsored by Lundbeck, to study the
preventive effect of the PACAP antibody in migraines.
How was the study with migraine patients organized, and
what stages did it include?
The study included patients with both episodic and chronic
migraines. We organized a multicenter study, where different
centers and researchers were responsible for recruiting
participants.
First, there was a screening to ensure that patients truly had
migraines. After that, they were given electronic diaries to record
all attacks and symptoms. This baseline phase helped confirm the
patient's suitability for the study and checked their readiness to
follow the instructions.
Then, patients were blindly randomized-they didn't know whether
they would receive the active drug or a placebo. Over the next
period, they continued to keep diaries so we could assess the
drug's effectiveness. After the treatment ended, a follow-up period
began to record any potential side effects. This is important for
evaluating the drug's safety not only during treatment but also
after it is metabolized.
In the end, we compared data from before and after treatment to
assess its impact on the frequency and intensity of migraines.
What was the main goal of the study, and what results
did it show?
The main goal of the study was to test the efficacy of high
doses of the drug (750 mg) compared to a placebo. The study showed
significant improvement in patients who received 750 mg of the
drug, confirming its effectiveness in preventing migraine attacks.
This result validated the concept and paved the way for the next
stage-Phase 3 clinical trials.
Phase 3 will include more patients and last longer to provide a
final check of the drug's efficacy and safety. If the results are
positive, the drug will become available on the market, offering a
new tool for migraine prevention.
The significance of the study is that over 15 years, it has
progressed from examining the effect of a single molecule on
migraines to the development of a potential new drug. The drug is
still administered intravenously, but work is underway to create a
form for self-injection under the skin, which will greatly simplify
treatment for patients.
How does this new drug differ from the recently
registered drug that targets another molecule?
The difference between the new drug and the recently registered
one is that they target different molecules and work through
different mechanisms. Imagine that each drug acts on the "doors" of
a cell, but each door leads to different parts of the system,
activating different processes. These drugs use different receptors
to prevent migraines.
This broadens the treatment options, allowing us to choose a
drug based on the individual needs of the patient. In the future,
combination therapy may reduce the number of migraine days even
further if one drug proves insufficiently effective.
It's also important to understand which receptor is the key
player in the pathway through which PACAP triggers migraines. This
will aid in the development of new, more precise drugs. We continue
to explore these mechanisms to offer more effective and specific
migraine treatments in the future. At the moment, this drug is not
available for clinical use, as it is still in the research
stage.
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