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Dr. Darwin Prockop believes adult stem cell therapies hold great promise for spinal cord injury patients and others and that Tulane can lead the way in offering patient treatments.
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While New Orleans residents decorate for the holidays
and anticipate the excitement of Mardi Gras, then Jazz Fest, Fourth of July, sports
seasons and lots of parades in between, medical researchers in the same city are
observing exhilarating dramas that could change the health and well-being of others.
Dr. Darwin Prockop, director of the Gene Therapy Center at
Tulane University Medical Center, says he's seen adult stem cells do things
that heretofore were considered counter to the laws of biology. Dr. Nicolas
Bazan, director of the Louisiana State University Neuroscience Center of Excellence,
and his colleagues discovered a non-narcotic pain reliever that does its job
without the side effects inherent in other analgesics on the market, including
addiction and liver damage. Still other researchers at the LSU Health Sciences
Center are refining a urine test to help doctors better detect cervical cancer
in HIV-positive women and have developed a drug capable of blocking the deadly
toxins of such infectious bacterial diseases as anthrax, sepsis, the pathogen
that causes urinary tract and other common infections, Ebola, diphtheria, yellow
fever, bronchitis and others. These are only a few of the hundreds of projects
underway in New Orleans' thriving medical industry.
As scientists, American citizens and even Congress debate the
moral, ethical and legal dilemmas of using embryonic stem cells to cure disease
-- which naturally has stymied laboratory research -- Prockop sidesteps those
headaches by focusing on adult stem cells and their potential to help people
paralyzed from spinal cord injuries. In general, stem cells extracted from bone
marrow (adult) and from non-implanted fertilized eggs or umbilical cord blood
(embryonic) have shown astounding promise in helping the body repair damage
to itself by transforming themselves into the specific body cells needed for
the job.
As the label implies, embryonic stem cells are generic cells
that change and multiply to form all the body parts of a human or animal; scientists
believe they could hold the key to therapies for everything from diabetes to
Alzheimer's. Adult stem cells, on the other hand, are considered more limited
in their potential because they already have differentiated into blood cells,
skin cells, etc. Adult stem cells are extracted from bone marrow and are capable
of creating all different kinds of blood cells and have for years been examined
for cancer treatments. Because embryonic stem cells are totipotent -- capable
of becoming any kind of body cell -- and can be maintained in their undifferentiated
state while being grown in a laboratory, many scientists and policymakers are
pushing for reduced restrictions and increased funding for such research. The
problem is opposition to the process because stem cells are extracted from a
fertilized egg. Although the egg has been fertilized in a petri dish, opponents
see the research as sacrificing human life. In a compromise, President George
W. Bush in August 2001 stipulated that only 78 pre-exiting embryonic stem cell
lines that originated from in-vitro fertilization could be used in research
funded by the national government. Researchers complain that the number of cell
lines available are far fewer, hard to get, take a long time to grow an adequate
number for experiments and are very expensive.
Prockop doesn't concern himself with all that, at least for
the moment. He has seen adult stem cells travel to damaged sites and repair
harmed tissue. He also has seen paralyzed rats regain mobility following stem
cell injections. As for arguments that embryonic stem cell research should be
favored because it appears more promising, Tulane's Prockop says he's undeterred
and will have a laboratory ready by January, in conjunction with the Louisiana
Gene Therapy Research Association to produce cells and develop a protocol that
can be tested in humans.
"Three-thousand people a year are permanently
paralyzed from injuries, mostly young males and mostly from motorcycle and car
accidents," Prockop says. "It costs about $450,000 per patient for the first
year, just for nursing home care. When it comes to these patients' lives, just
a little thing like regaining bladder control could change their lives. ...
Among these patients, the suicide rate is astronomical."
He admits, however, that he's hoping for more
than bladder control. "We've had good results in rat models," he says. "We paralyze
them, we put in the (stem) cells and the rats walk. I've seen it." His lab also
is working on a system to make adult stems cells grow more quickly in the petri
dish, which would be required for stem cell therapies to become widely used.
The next step is to obtain FDA approval for a protocol to use the adult stem
cells in paralyzed human patients.
"There's always a risk when you go from animal
to human (applications)," he says. "You have to be ready for the unexpected.
The results we've seen already give us hope of going to other diseases where
the central nervous system is damaged."
Although he's focusing on spinal cord injuries,
Prockop says he's witnessed the potential of adult stem cells to metamorphose
into things other than blood cells and believes the potential may be far less
limited than pro-embryonic stem cell research advocates portray.
"We're dealing with amazing cells; we just
don't know their limits," says Prockop, who considers stem cells' ability to
rejuvenate tissue the body's "fountain of youth." "Stem cells can become many
different kinds of cells. The embryonic stem calls can become anything. We don't
know if our (adult) cells can become everything else in the body -- we're close
to that -- but we know they can become lots of different things. It seems that
if you damage almost any tissue, these cells will go there and repair it. I
just couldn't believe it."
Stem cell research has been conducted for
half a century, but has only been investigated as a therapy for about 10 years,
he says, and the Tulane lab was one of the first to explore them as a possible
therapy. Already the knowledge gained has been counter to stated medical conventions
"The things we've discovered about these cells
over the last five years goes against what the textbooks have said for 100 years
... against the stated laws of biology," Prockop says. "The textbooks said this
will not happen, but we saw it happen. It took a long time to convince people,
but that's the excitement of research."
Less controversial but no less important to
those who need it is a pain reliever patented by LSU's Bazan to be developed
and marketed by St. Charles Pharmaceuticals, a biotech-pharmaceutical start-up
based in New Orleans. The new drug, called SCP-1, is going through clinical
trials and may be ready for the market by 2004.
"It's similar in many ways to Tylenol, but
it doesn't have the side effects that Tylenol sometimes has," Bazan says. Other
pain relievers also cause problems for patients because they are either made
with narcotics, are addictive, can collect toxins in organs or damage the gastro-intestinal
tract. "This is non-narcotic, non-addictive and it doesn't damage the liver
or the GI tract. It's safe," Bazan says. "People will be able to treat chronic
diseases without all the toxic side effects." He also is proud of the homegrown
business and it's potential economic boon to New Orleans. He also is one of
a team of scientists who have developed new drugs to treat stroke and Alzheimer's,
although they are not being tested yet in humans.
More exotic but no less useful is a drug developed
at the LSU Health Sciences Center that blocks sometimes-lethal toxins secreted
by bacteria that cause diseases such as anthrax, Ebola, clostridium, diphtheria,
HIV-1, infectious bronchitis, yellow fever, urinary tract infections, dermatitis,
and sepsis, which kills an estimated 200,000 of the 750,000 Americans who get
it each year and is a leading cause of death among the critically ill.
The drug, called D6R, works by blocking the
enzyme that activates bacterial and viral toxins. A study of the drug and its
efficacy has been published in the current issue of Infection and Immunity,
but researcher Iris Lindberg says it's a long way from clinical trials in humans.
"I think it will be useful for acute infections,"
she says. "but I don't think we'll be able to inhibit this enzyme (that triggers
the toxins) in the long term. We desperately need drugs that interfere with
the toxins."
Studies have shown that the drug has saved
the lives of people infected with diphtheria. "It was a dramatic outcome, but
it's not 100 percent," she says. "Half the animals tested survived what normally
would be a lethal dose of diphtheria toxin.
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Stem cells have shown astounding promise in helping the body repair damage to itself by transforming themselves into the specific body cells needed for the job.
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"What we're looking at is a shift, a new kind
of thinking to block the furon enzyme required for entry of the toxin into the
cell instead of blocking reproduction of the bacteria." The toxins, she says,
are what kill cells.
"[Scientists] have been interested in the
enzyme from way back, and a method that is fairly new is to look for inhibitors.
I thought it wouldn't work, but it does. What's exciting is when you think it
won't work ... then it actually does. You have a lot of experiments to find
out that things don't work. Then it's fun when you get a 'Eureka.'"
Microbiologist Joeli Brinkman says an innovative
urine test developed at the LSU Health Sciences Center may prove a lifesaver
for detecting cervical cancer early in HIV-infected women. Results of her team's
research on the subject were published in the Journal of Clinical Microbiology
in September. The urine test detects human papillomavirus (HPV), which causes
some of the most common viral sexually transmitted diseases worldwide and has
been linked clinically with cervical cancer. HIV-positive women suffer high
rates of HPV infections, experience more multiple infections and are at high
risk for cervical cancer. The urine test would give health workers a screening
option to the invasive cervical swab.
"Mostly in research, what you do is put pieces
in a puzzle," she says. "What you're looking at is scientific framework, coming
along with your piece and adding to that. This is extra. You can go directly
to a therapeutic application.
"Science is a great occupation. You're constantly
asking questions, then you go to the lab and answer them. There's very little
routine."
