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Life Savers 

Medical research being conducted in New Orleans holds promise for saving lives and improving their quality as well.

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.

"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."

click to enlarge 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.
  • 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.
click to enlarge 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.
  • 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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