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NIH Supports Tam’s Project
to Characterize Components
in Antibiotic of ‘Last Resort’
In the fight against drug-resistant infections, UH College of
Pharmacy Associate Professor Vincent H. Tam, Pharm.D.,
BCPS, is working to understand the various components of a
potent antibiotic of “last resort” in an effort to develop safer, more
effective formulations of the drug and better strategies for its use.
Research NEWS
The antibacterial drug Polymyxin B – which attacks bacteria
by altering the permeability of the outer membrane, leading to
cell death – was introduced for clinical use in the late 1950s,
before federal regulations required manufacturers to file detailed
documentation on their products’ composition and formulations.
Polymyxin B and many other drugs developed before the advent
of modern disclosure regulations were “grandfathered” in, and
manufacturers were not required to disclosure the specific
components in their formulations.
Although highly effective against many gram-negative bacteria,
Polymyxin B is considered an antibiotic of “last resort” because
it has the disadvantage of being more toxic, particularly to the
kidneys, than newer drugs. However, as bacterial strains develop
resistance to all other antimicrobial agents, more toxic drugs
like Polymyxin B may be called upon to treat severe, persistent
infections.
“If we were to develop this drug today, there is no way it could get
approved by the current approval standards because there is so
much we don’t know about it,” Tam said. “We now have a medical
need for this drug, which makes a compelling argument to study
its basic properties so we know how to most optimally use it.”
In addition to studying the individual components in
commercially available formulations of Polymyxin B, the project
team will evaluate whether new formulations or new strategies
could be developed to reduce toxicity while maintaining efficacy.
For example, strategies employing a combination of such factors
as dose, dosing frequency and duration of therapy could be
Matt White photo
Associate Professor Vincent Tam and graduate student Kamilia Abdelraouf are
working to characterize the components of Polymyxin B, an older antibacterial
that is highly effective against bacterial infections but also more toxic to the
patient.
used to control the infection with minimal collateral damage to
the kidneys or other organs. Another option could involve premedicating
or buffering the kidneys before Polymyxin B is used to
protect the tissue from damage.
Tam is collaborating with UHCOP Professor Ming Hu, Ph.D., on
the project, which is being funded by a three-year, $450,000 grant
from the National Institute of Allergy and Infectious Diseases.
Tam is believed to be the first Pharm.D. translational researcher
within the college to receive a direct NIH award as principal
investigator in the past decade.
NIH Grants $353K Supplement to Asthma Project by Bond, Knoll
The investigation by UH College of Pharmacy researchers
into the use of beta-blockers as a therapeutic for mild, chronic
asthma recently received a welcome boost, with the National
Institutes of Health providing a $353,000 administrative
supplement for the project.
Earlier this year, Professor Richard A. Bond, Ph.D. (’88), B.S.
(’83), and Associate Professor Brian J. Knoll, Ph.D., received a
two-year, $682,000 grant from the National Institute of Allergy
and Infectious Diseases for their study into the mechanisms that
resulted in decreased airway hyperresponsiveness and produced
broad anti-inflammatory effects in animal models of asthma.
The decrease in airway hyperresponsiveness also was seen in
two small clinical trials treating mild asthmatics.
In one segment of the project, the lab of longtime collaborator
Burton F. Dickey, M.D., professor and chair of the Pulmonary
Medicine department at M.D. Anderson Cancer Center, will
produce transgenic mice to test the team’s hypothesis that
a primary target cell for the effect of beta-blockers are the
epithelial cells lining the airway instead of the underlying
smooth muscle tissue as suggested by some researchers.
The supplement brings the total support for this phase of
their research to $1.04 million, which was funded through
the American Recovery and Reinvestment Act of 2009 (aka
“Stimulus Package”).
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