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Human Therapeutics Bacteriophages were first used
therapeutically in humans during 1919 (shortly after their
discovery), to treat severe cases of bacterial dysentery in four
children in Paris, France. All of the treated children recovered
from what otherwise could have been a fatal infection. The study
was conducted in close collaboration with Felix d’Herelle, one
of the discoverers of bacteriophages. However, it was not
published in the scientific literature until several years later
(reviewed in 1). Therefore, the first published
report about using bacteriophages to treat human infections
dates to 1921, when Richard Bruynoghe and Joseph Maisin
published a short paper describing the successful use of
bacteriophages to treat staphylococcal skin disease in six
patients 2. Since that time, phages have been used to treat
bacterial infections in millions of humans in a variety of
clinical settings. Phages have been administered to humans:
- Orally, in tablet and liquid formulations
- Rectally
- Locally (skin, eye, ear, nasal mucosa, etc.), in tampons,
rinses and creams
- As aerosols and intrapleural injections
- Intravenously
There have been no reports of serious complications
associated with the use of phages in such settings 1,3.
Therapeutic phage preparations also were produced in the
U.S.A. during the 1930s and 40s, by well-known pharmaceutical
companies, including Eli Lilly, E. R. Squibb and Sons, and
Swan-Myers (a division of Abbott Laboratories). However, the
advent of antibiotics caused interest in phage therapy to
decline in the West, and therapeutic phage applications were all
but abandoned in the United States, Western Europe and the rest
of the developed world. At the same time, therapeutic phage
applications continued in the FSU and many Eastern European
countries, where therapeutic phage preparations are currently
available for sale in pharmacies and specialized research
centers and clinics.
The rapid and alarming emergence of antibiotic-resistant
“superbugs” has rekindled interest in phage therapy in the West.
Indeed, the increasing emergence of antibiotic-resistant
bacterial pathogens may have very serious public health
ramifications, and it may seriously impact the way medicine is
practiced today in much of the world. The problem was emphasized
recently in a report by a special Task Force co-chaired by the
CDC, FDA and NIH, which stated that “The world may soon be faced
with previously treatable diseases that have again become
untreatable, as in the pre-antibiotic era.” Intralytix believes
that phage therapy can be a potent tool for dealing with
bacterial infections of humans and domesticated animals, and
that phage therapy will help to reduce problems caused by the
emergence of antibiotic-resistant bacteria (i.e., bacteria that
are untreatable with currently available antibiotics). In many
cases, it may be the only safe and effective approach currently
available for saving a patient’s life.
Intralytix is developing several phage preparations for
preventing and treating bacterial diseases of humans. The
company’s first human health product is a topical preparation
(designated WPP-201™) for treating bacterially-infected skin
ulcers commonly found in diabetic patients. The product will
address an urgent, unmet medical need: in the U.S.A., ca. 90,000
amputations per year are due to complications precipitated by
diabetic foot ulcers. Although circulatory impairment plays a
major role, the majority of these amputations are necessitated
by infections that are resistant to current, state-of-the-art,
antibacterial therapies. The company is preparing for WPP-201™’s
first clinical trial in humans, and we expect the outcome to be
very favorable.
Another example of a phage-based, antibacterial,
wound-healing preparation being developed by Intralytix, Inc. is
a product called PhagoBioDerm™. PhagoBioDerm™ is a biodegradable
polymer matrix (composed of naturally-occurring amino acids)
impregnated with naturally-occurring bacteriophages (and,
optionally, with other active ingredients), which can be used to
treat bacterial infections of chronic wounds, injury-related
wounds (including combat-associated wounds caused by gunshots
and mine explosions), and burns. PhagoBioDerm™ has been used
successfully/is currently used to treat infected wounds in the
Republic of Georgia (some of those therapeutic uses are
described in the scientific literature 4-6).
Areas of Practical Applications
Properly developed and manufactured phage preparations can be
invaluable in dealing with bacterial infections of humans, when
used as:
- a prophylactic and/or therapeutic agent to reduce the
levels of bacterial pathogens in infected wounds and to
improve healing of those wounds. Intralytix, Inc. has
developed a phage mixture (“phage cocktail”) for such
applications (WPP-201™), and the company is planning to
initiate, in the near future, human clinical trials of the
product.
- an active component of a topical, biodegradable polymer
matrix designed to assist in wound healing. Intralytix has
received a patent for PhagoBioDerm™ (a biodegradable matrix
impregnated with bacteriophages), which can be invaluable for
treating infected wounds. The company expects to initiate
clinical trials of the preparation in conjunction with the
WPP-201™ trials, or shortly after the WPP-201™ trials are
completed
- a prophylactic and/or therapeutic agent against bacterial
diseases, especially those caused by multidrug-resistant
bacteria against which there is no currently effective
prophylaxis or treatment. Some examples of such infections
include those caused by vancomycin-resistant enterococci,
methicillin-resistant Staphylococcus aureus, and
multidrug-resistant Pseudomonas aeruginosa.
- a prophylactic and/or therapeutic agent against bacterial
diseases where biofilm formation may complicate conventional
therapy. Some examples include those caused by multidrug-resistant
P. aeruginosa; e.g., pulmonary infections often found in
cystic fibrosis patients, and chronic wound infections.
- a prophylactic and/or therapeutic agent designed to reduce
or eliminate the bacteria that cause dental caries,
gingivitis, and bad breath; e.g., phage-containing mouthwash
and toothpaste.
References:
1. Sulakvelidze, A., Alavidze, Z., and Morris, J. G., Jr.,
Bacteriophage therapy, Antimicrob Agents Chemother 45 (3),
649-659, 2001.
2. Bruynoghe, R. and Maisin, J., Essais de thérapeutique au
moyen du bactériophage du Staphylocoque, J Compt Rend Soc Biol
85, 1120-1121, 1921.
3. Alisky, J., Iczkowski, K., Rapoport, A., and Troitsky, N.,
Bacteriophages show promise as antimicrobial agents, J Infect 36
(1), 5-15, 1998.
4. Jikia, D., Chkhaidze, N., Imedashvili, E., Mgaloblishvili,
I., Tsitlanadze, G., Katsarava, R., Glenn Morris, J., Jr., and
Sulakvelidze, A., The use of a novel biodegradable preparation
capable of the sustained release of bacteriophages and
ciprofloxacin, in the complex treatment of multidrug-resistant
Staphylococcus aureus-infected local radiation injuries caused
by exposure to Sr90, Clin Exp Dermatol 30 (1), 23-26, 2005.
5. Markoishvili, K., Tsitlanadze, G., Katsarava, R., Morris, J.
G., Jr., and Sulakvelidze, A., A novel sustained-release matrix
based on biodegradable poly(ester amide)s and impregnated with
bacteriophages and an antibiotic shows promise in management of
infected venous stasis ulcers and other poorly healing wounds,
Int J Dermatol 41 (7), 453-8, 2002.
6. Stone, R., Bacteriophage therapy. Stalin's forgotten cure,
Science 298 (5594), 728-31, 2002.
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