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Improving treatments for tuberculosis
The battle against sleeping germs
We thought that we had conquered tuberculosis, but we were wrong. A third of the world’s population is infected with
these dangerous pathogens. Bayer’s scientists are currently conducting clinical trials to evaluate a possible use of the
antibiotic moxifloxacin to control this insidious disease. They are also working with partners in a global network to develop new treatment strategies against the dangerous tuberculosis bacteria.
For a long time everything seems to be
fine, but appearances are deceptive.
It often takes years for people to realize that they have tuberculosis. This is
because when our immune system is fully
intact and sufficiently strong, it keeps
the bacteria in check. But as soon as the
body is infected by other germs, and the
immune defense mechanism is distracted
by other tasks, the pathogens wake from
their enchanted slumber: the centers of
inflammation, also called tubercles, suddenly become active and break out.
Standard treatment today
­consists of four antibiotics
Thousands of pathogens overwhelm the
body, resulting in the dangerous condition known as “open tuberculosis.” And
although the pathogen has long been
known to medical science, tuberculosis (TB for short) is still very difficult to
treat. “At present, TB patients have to
take a standard therapy of four different
20
Someone dies of TB
every 20 seconds.
seconds
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Clinically pure: the antibiotic moxifloxacin
is prepared for clinical testing under sterile
conditions. If these trials are successful,
­pharmacologists like Diana Gross will be
able to produce the drug for TB patients at
affordable prices.
antibiotics for six months,” comments
Dr. Martin Springsklee, Head of Global
Medical Affairs Anti-infectives at Bayer
HealthCare. Although only about 10 percent of people with TB have the open
form, their infectious potential is high. If
left untreated, the disease usually results
in death or at least in serious and lasting
damage.
Another problem is that the available
TB drugs are becoming less effective.
A patient who contracts tuberculosis today will be given drugs that were
developed in the 1960s. “But bacterial
strains have changed in the meantime,
and have become insensitive to many
of the conventional antibiotics,” says Dr.
Maria-Luisa Rodriguez, Global Project
Leader for the development of moxifloxacin in tuberculosis at Bayer HealthCare.
This feared resistance usually happens
when patients abandon treatment or
stop taking the drugs before completing
the course. Then the strongest pathogens
are most likely to survive and reproduce.
And the drugs available are no longer of
any use against tuberculosis caused by
resistant germs. “This is why we urgently
need new active substances and approaches to treatment,” says Mel Spigelman,
Director of the Global Alliance for TB
Drug Development, or TB Alliance for
short. This organization promotes the
worldwide development of drugs to treat
tuberculosis. Says Spigelman, “We are
bringing research institutions, donors
and the pharmaceutical industry to the
same table.”
Moxifloxacin could help
tuberculosis patients
Bayer HealthCare has also joined the TB
Alliance, supporting the fight against
tuberculosis since 2005 by making its
antibiotic moxifloxacin available to the
TB Alliance for clinical studies. Says
Springs­klee, “This substance is already
being used to treat serious lung infections such as pneumonia.” This was a key
starting point for TB research: scientists
successfully tested the efficacy of moxifloxacin on tuberculosis bacteria, which
are easily transmitted via classic droplet
Photos: Sabine Bungert/Bayer AG (3), SPL/Agentur Focus (1), University of St. Andrews (1), TB Alliance (1)
Tuberculosis Medicine
Immune system in action: an eater cell – a macrophage – devours TB bacteria (orange) in the human body.
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“We urgently need
new active substances
and approaches to
treat tuberculosis.”
Mel Spigelman,
Director of the Global Alliance
for TB Drug Development
infection when an infected person coughs
or speaks, and transmission often goes
unnoticed. This is also why the disease
mainly affects the lungs, but in principle
any organ can be attacked. According to
Springsklee, “We found that moxifloxacin
can kill tuberculosis bacteria very quickly,
which makes it a good candidate for a
possible treatment.”
Together with other partners, TB Alliance’s and Bayer HealthCare’s scientists
launched the REMox TB trial, in which
moxifloxacin is being tested in around
1,900 patients with tuberculosis as part
of a four-drug therapy. “The trial is taking place at over 48 sites in nine countries, making it one of the biggest efforts
in modern tuberculosis drug research,”
Spigelman reports. Bayer’s scientists are
contributing not only a drug but also
their entire body of development exper-
tise. “We are committed to producing and
marketing the drug at affordable prices
for patients with TB if the REMox TB trial
is successful,” Rodriguez says. This would
be an important milestone in tuberculosis treatment, “because someone dies of
TB every 20 seconds. Up to nine million
people contract the disease every year,”
Springsklee explains.
Tuberculosis bacteria use
­numerous biological tricks
Bayer HealthCare and TB Alliance want
to cut the length of treatment from six
months at present to four months. This
would be a considerable advantage,
“because a shorter course of treatment
increases the likelihood that patients
complete the course,“ Rodriguez comments. This is essential to combat bacte-
Tuberculosis bacteria recognize no frontiers
Worldwide, up to 9 million people contract tuberculosis every year. Tuberculosis is particularly widespread in sub-Saharan Africa, Asia and
South America as well as in countries where many people are infected with the immunodeficiency disease HIV, as these disorders mutually
potentiate each other. The world map shows the estimated number of new cases of tuberculosis in 2011. Bayer’s scientists are collaborating in a research program with the TB Alliance to help reduce the number of tuberculosis patients worldwide.
Estimated number of
new cases of TB per
100,000 inhabitants
0 - 24
25 - 49
50 - 149
150 - 299
≥ 300
Not applicable
No estimate available
Source: Global Tuberculosis Report 2012, WHO, 2012.
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Tuberculosis Medicine
Stephen
Gillespie
research talked to Professor Stephen
Gillespie from the University of St. Andrews,
Scotland, about tuberculosis
“A serious chronic
disease”
How do people become infected with tuberculosis, or TB
for short?
The disease is caused by mycobacteria, which primarily spread
from person to person as a droplet infection. However, not everybody who is a carrier of the pathogens expels them in his or her
exhaled breath. That only happens in people with open tuberculosis: here, the disease source in the lungs is connected with the
airways and the bacteria can escape into the exterior.
How can the disease be treated?
Patients are put into isolation until they are no longer infectious.
At present, combination treatment with various antibiotics is
required to kill all the bacteria. However, we urgently need new
active ingredients to get resistant pathogens under control.
Research groups all over the world are working intensively on
new active ingredients for tuberculosis.
Why is tuberculosis so dangerous?
Expert check: while Diana Gross (top photo) controls and checks tablet
production, Dr. Martin Springsklee and Dr. Maria-Luisa Rodriguez plan
the clinical trial and other projects that could help TB patients in future.
rial resistance, because the tuberculosis
germs, known as mycobacteria, operate
by means of biological tricks: the bacteria
can freeze their metabolism, going into
a kind of sleep. This makes them almost
inaccessible to drugs, because the active
substances usually attack microbes’ vital
processes.
The initial results of the REMox TB
trial should be available in early 2014. But
one positive side effect has already been
achieved. The trial has led to the creation
of a professional medical infrastructure
that will not only benefit TB patients
Open TB is a very serious, chronic disease. After some time,
the patients are exhausted to the point that their lives are at
risk. They can no longer work and their families are reduced to
poverty. Many of them are unable to afford treatment.
but will also serve as a valuable basis
for future projects. A global network for
drug research and development is vital,
as drug-resistant bacteria do not recognize national borders. Globalization has
therefore made tuberculosis a disease
that could nowadays in theory affect
anyone.
Bayer’s scientists are supplying important weapons in the fight against this
insidious disease in the form of their
active substance and their knowledge.
­Initiatives such as the worldwide effort to
combat malaria are also under way,
because both tuberculosis and malaria are
neglected diseases which mainly affect
poverty-stricken and already weakened
individuals.
Multimedia report on South Africa:
tuberculosis
http://bayer.com/re2505
www.research.bayer.com/tuberculosis
More information on this topic
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