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This page:
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Bioactive molecules
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Cancer drug from marine bacteria
• Antitubercular drug
• Cures from squid eggs
• Hope
for Alzheimer's
Other developments:
Fisheries
& aquaculture
Agriculture
& industry
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Marine Life — a
source for potential cures
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The
problems.
Medical professionals and the public are eager for new sources of
medicines that can address some of our top health issues. For instance,
contemporary approaches to drug development have been unsuccessful
in treating several forms of cancer, arthritis, and Alzheimer's
disease. Additionally, while bacterial infections can be treated
with antibiotics, relatively few compounds are available to treat
viruses, parasites, and fungi, which are responsible for thousands
of deaths each year. These problems are compounded by the fact that
terrestrial organisms now yield few new substances with medicinal
properties. Lastly, one of the most pressing health issues, one
with global ramifications, is the rising resistance to antibiotics
among humans and animals.
Potential
solutions. The earth's oceans
are the last great frontier in the search for plants and organisms
with pharmaceutical value. Just within the past 30 years, efforts
began to define the "chemistry" of marine plants and animals.
By the mid 1980s, efforts turned toward potential biomedical applications
of the novel chemicals found in sponges and related colonial marine
invertebrates. In this process, over 2,500 structurally diverse
compounds have been found in marine plants and animals, and several
have been successfully interfaced with the pharmaceutical industry.
Currently, a number of drugs from marine organisms are undergoing
clinical trials as anticancer treatments. In addition, scientists
have isolated and chemically characterized many unique compounds
that have exhibited possible efficacy against fungal infections,
Alzheimer's, strokes, tuberculosis, Cystic fibrosis, viral infections,
and other diseases. It is envisioned that continued exploration
and research will lead to many organisms with unusual structures
and unique compounds with medicinal promise.
In
the following section we have listed Sea Grant projects that are
reaching fruition.
Periodically, we will update this section with new developments.
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New
Developments in Biomedicine |
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Discodermolide
a compound derived from a deep sea sponge, shows potent anti-tumor
activity. Above, leading researcher, Dr. Shirley Pomponi prepares cells
for culture.
Photo:
Harbor Branch Oceanographic Institution, Florida
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Bioactive
molecules with anti-tumor activity
Many
bioactive molecules produced by marine invertebrates have exhibited
potent anti-viral and anti-tumor activity.
One tunicate compound (ecteinascidin 743), investigated
through Florida Sea Grant, is undergoing clinical trials in
the United States and Europe for the treatment of cancer. Another
compound, discodermolide, derived from a deep sea sponge,
is in advanced preclinical trials with a major pharmaceutical
company. A third compound, eudistomins, produced by a
tunicate that lives on mangrove roots, also holds promise as
a potent anti-tumor treatment.
The
natural supply of these compounds is a limiting factor to their
pharmaceutical development by conventional means. Each species
produces a minute amount of the desired bioactive molecules,
and the species could not withstand the massive collection needed
for testing and production. Therefore, the Florida researchers
involved in these projects are attempting to create alternative
sources of these bioactive molecules. One possibility under
investigation is using cell culture to develop a cell line that
will produce the desired compound.
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For
more info on this topic, see these articles from Florida Sea
Grant's Fathom newsletter.
Process
for Lab-Grown Eudistomins Tested (1996)
Cell
Culture Offers Alternative to Harvesting Sea Creatures (1996)
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Anticancer
compounds, are produced by the bacteria living in bryozoan,
a minute animal that forms moss-like, branching colonies.
Photo: California Scripps
Institution of Oceanography.
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Anticancer
drugs from the bacteria inside an animal...
Bacteria
living inside a bryozoan, a moss-like marine animal, are the source
of bryostatins, a new family of anticancer drugs now in clinical trials
for humans. Dr. Margo Haygood, with support from California Sea Grant,
identified the genes that code for the production of bryostatins and
then showed that these genes are expressed in the bacterium Candidatus
Endobugula sertula ( E. sertula). Before this, researchers
had thought the source of bryostatins was the bryozoan itself.
Haygood's overall research efforts
are aimed at solving the dilemma of supply. As with other marine organisms
with pharmaceutical potential, the production of bryostatins is inhibited
by the natural supply of the the marine organisms and the minute amount
of bioactive compounds each creature produces. Haygood first attempted
to overcome this hurdle by culturing E. sertula. When this failed,
she sequenced E. sertula's genes. Her strategy is to find
an easy-to-grow nonmarine bacteria whose genetic apparatus will accept
the gene cluster from E. sertula; the transgenic bacteria would
then synthesize the proteins that produce bryostatins.
Haywood's team has made more progress
than any other research group in developing a method of producing marine
natural compounds in commercial quantities. If successful, their strategy
for reproducing a bioactive compound could help multiple research efforts
in marine biomedicine. Their work has led
to a U.S. patent, and the results have led to continuing research supported
by the National Cancer Institute and the Department of Defense Breast
Cancer Research Program.
(Excerpted from California Sea Grant.
See article
and photos PDF).
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Enhancing
antitubercular properties of a marine product
Puupehenone
is a bioactive marine natural product obtained from a sea sponge. Puupehenone
and its numerous derivatives have very promising antitubercular, anticancer,
and antibacterial properties. A Mississippi-Alabama
Sea Grant project is focused on enhancing the anticancer and antitubercular
properties through combinatorial chemistry. They will detect the most
active compounds and resynthesize them on a larger scale. The enhanced
compounds will be tested for anticancer activity at the National Center
for Natural Products Research and at Biomar Inc. in Spain, and tested
for antitubercular activity at the Institute for Tuberculosis Research
in the College of Pharmacy at the University of Illinois.
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research manuscript:
Marine Natural Products as Antituberculosis Agents (El
Sayed KA, Bartyzel P, Shen X, Perry TL, Zjawiony JK, Hamann MT)
summarizes attempts to characterize additional structural classes
that could serve as lead antituberculosis agents. |
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Dr.
David Epel and his team have been investigating the protective paste
on squid eggs for their antibacterial properties.
Photo:
California Scripps Institution of Oceanography.
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Antibiotics
from Squid Eggs?
To protect their eggs from fungi, bacteria, and
parasites during incubation, female squid coat their eggs with a paste
made up of a dense bacterial community. Marine biology professor Dr.
David Epel of Stanford University has been investigating the antimicrobial
properties of the squid's secretions in the hopes that the bacteria
will lead to new pharmaceuticals.
Dr. Epel and his team, supported by California
Sea Grant, have discovered two previously unknown types of bacteria
from the California market squid's eggs and it accessory reproductive
glands. Using a new molecular technique, Epel and postdoctoral researcher
Dr. Todd Ciche next identified eight more species of bacteria on the
egg sheath. Cultures of the bacteria revealed that only one of the species
produced antibacterial compounds. Epel and Ciche hypothesize that the
bacteria work in concert, communicating through chemical signals, to
produce antibiotic and anti-fungal compounds. Their future work will
focus on isolating and describing the antibiotics present in the egg
coatings.
(Excerpted from California Sea Grant's web site.
See article
and photos PDF).
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Dr.
Alejandro Mayer has patented a chemical from a marine sponge that might
lead to new nonsteroidal anti-inflammatory drugs.
Photo:
California Scripps Institution of Oceanography.
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Possible
Hope Against Alzheimer's Disease
In his investigation of 38 compounds purified
from tunicates, sponges, and other marine organisms, Dr. Alejandro Mayer,
from Midwestern University, Illinois, has discovered several compounds
that show pharmaceutical promise for multiple sclerosis, Alzheimer's
disease, and head injuries. Dr. Mayer's research, supported by California
Sea Grant, focused on learning if any of the marine compounds could
suppress, inhibit, or control the release of neurotoxic mediator compounds
in the brain. Although mediator compounds are released by the brain's
defense system, a network of microglia cells, to protect against infection,
scientists have found that the release of too many mediators damages
neurons. It is believed that mediator compounds may exacerbate or help
cause Alzheimer’s disease, stroke, and multiple sclerosis.
Of the 38 tested compounds, three inhibited
the release of a mediator that can cause neuroinflammation and a free-radical
type of mediator that might contribute to Alzheimer’s disease.
Moreover, Dr. Mayer found that the marine chemical Manzamine A, extracted
from a marine sponge, inhibits mediator formation in microglia isolated
from newborn rats without killing healthy cells. It is hoped that Manzamines
will lead to the development of a new class of nonsteroidal anti-inflammatory
drugs that specifically target mediator production.
(Excerpted from California Sea Grant. See article
and photos (PDF file).
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