Monday, June 28, 2004

Scientists make stem cell breakthrough

Cures for diabetes, Alzheimer's and spinal cord damage could be as little as five years away, after the landmark creation of more than one million stem cells from a single Australian embryo.

The work of Sydney IVF's research laboratories, the achievement is the first time Australian scientists have cultured embryonic stem cells from an Australian embryo on home turf.

Although legal hurdles have set the nation's stem cell research two years behind the United States-led cutting edge, Sydney IVF medical director Professor Robert Jansen is confident of catching up.

"There are several hurdles, ... but there's a small chance it will be inside five years," Jansen said of the possible therapeutic uses of cultured embryonic stem cells.

One of those hurdles has already been overcome by research director Dr Tomas Stojanov and his team - the need to grow the cells on human "feeder layers" rather than culturing them on mouse cells.

However, safety and anti-contamination guidelines are yet to be drawn up, the issue of tissue rejection by stem cell recipients must be overcome and scientists need to work out how to generate enough cells to meet demand.

"At the moment ... there are not enough lines for research and future clinical use," Stojanov said.

The Sydney team is now trying to automate the process of extracting viable cells from unwanted five-day-old embryos, so they can produce stem cells in much greater volumes.

Millions of cells would need to be injected as a treatment for just one patient, Stojanov explained.

The cells cultivated by the Sydney IVF team remain undifferentiated, meaning they have the potential to turn into any cell in the human body.

There's already a huge demand for the IVF clinic's stem cells, from medical research scientists who plan to turn them into nerve, heart and pancreatic cells, among others.

"The obvious direction of the research is the treatment of serious childhood and adult diseases where cells are lost or damaged or destroyed and can't be replaced by the body's own stem cells," he said.

"That's true of some tissues more than others, particularly the brain and spinal cord (and) in childhood diabetes, where the insulin-producing cells of the pancreas have lost their function or are so depleted in number they can't do their job."

Conditions that have the potential to be treated with stem cells include Alzheimer's, Parkinson's disease, multiple sclerosis, motor neurone disease, spinal cord and brain damage, diabetes and heart conditions.

The clinic won licences in April to cultivate stem cells from as many as 600 embryos, after the federal government legislated to allow research on human embryos.

In May this year the clinic thawed an embryo frozen in March 2000, then extracted cells from its centre and placed them on a human cell-based "feeder" culture to grow.

There are strict criteria for the harvesting of stem cells - the embryos must have been created for the purpose of assisted reproduction and the permission of its parents must be obtained.

The embryo also must be one that would otherwise have been discarded, but that doesn't excuse the research in the eyes of Right To Life Australia or the Catholic church.

"Two wrongs don't make a right - they should not have created excess embryos in the first place," said Margaret Tighe, president of Right To Life Australia.

"Quite clearly this involves the destruction of a very small human being for the benefit of other human beings."

Even if embryonic stem cells could save a loved one, Tighe said she would remain against the research going ahead.

The Life Office, an agency of the Catholic Archdiocese of Sydney, condemned the research as unethical and scientifically unnecessary.

"Although embryonic stem cells have been used for research around the world for some time, there have been no human trials and there are still no approved medical treatments," Life Office executive officer Dr Brigid Vout said.

"It is research using stem cells from adults which holds the greatest therapeutic promise.

"Adult stem cells are already being successfully used to cure disease or overcome injury in patients."

Jansen acknowledged that a cure is yet to be effected using embryonic stem cells, but pointed out that the research had only been given legislative approval after vigorous and protracted debate.

"I'm very proud that Australia has risen to the occasion legislatively to permit this," he said.

Prime Minister John Howard also reiterated that the work was legal.

"I support very much the law that was agreed upon at the premiers' conference in 2002 and I want that law observed," Howard told reporters.

More than half of the clients at Sydney IVF were in favour of donating their excess embryos for stem cell research, Jansen added.

"I think most couples, when they've had such an amount of difficulty getting pregnant, realise that their success has depended on people who've donated embryos before for research," he explained.

The couple who donated the embryo used to cultivate the stem cells revealed today were "absolutely delighted", Jansen said.

"They expreere entered into a scientific study," he said.
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Saturday, June 12, 2004

New Nerve Cells

Every year, thousands of people end up paralyzed when their spinal cords are injured. Right now, these patients almost never fully recover. But, as this ScienCentral News video reports, one nanotechnologist says there may be a way to grow back injured nerve cells?and repair damaged spinal cords, so that paralyzed patients can leave their wheelchairs behind.

Tiny Scaffolding

Some of the 250,000 Americans who have been paralyzed by spinal cord injuries are pressing medical researchers for a cure. The most prominent is actor and director Christopher Reeve, who was paralyzed after a fall from his horse in 1995. At a symposium on spinal cord research at Rockefeller University, held on November 24, 2003, Reeve commented on "a certain frustration" that he and other paralyzed patients feel over the current pace of American research, which has been hampered by political debate over the use of stem cells. "I think that we need to inject more urgency into the whole process here," Reeve observed.

Another speaker at the Rockefeller symposium was Michael Di Scipio, 34, who was paralyzed after a diving accident in July 1999, when he was 29. A single father, he says his two young children have been injured, too?by what he can't do: "Not being able to run around and play with them, hold them, tickle them, tuck them in, give them a kiss good night. Things we're supposed to do as parents."

One reason that prospects for recovery are dim at present for patients with spinal cord injury is that unlike other cells, nerve cells, or neurons in the central nervous system (the brain and spinal cord) are unique in that they cannot replicate themselves in their mature state. So repairing spinal cords means finding a way to get nerve cells to grow back across the gap in a spinal cord that has been severed.

Some prominent nanotechnologists are hard at work on the problem. Samuel Stupp is professor of chemistry at Northwestern University, where he is director of the Institute for Bioengineering and Nanoscience in Advanced Medicine. He and his research team say they have engineered a nanoscale scaffold upon which new neurons can grow and bridge the gap in a damaged spinal cord.

Stupp starts out with a liquid made up of negatively-charged molecules, which normally would repel each other. "We started with a very simple concept," explains Stupp, "asking, can we design a material from the bottom up, that is made of nanostructures that assemble themselves?? When the negatively-charged liquid comes across positively-charged molecules found in living tissue, such as calcium or sodium ions, they instantly clump together into a gel. This gel forms into tiny fibers, or tubes, each about five nanometers wide and several hundreds of nanometers long. Gabriel Silva, a member of Stupp's research team, explains that each fiber has a hydrophilic, or water loving, core and a hydrophobic, or water-repelling, surface. In water, the fibers assemble themselves into miniature scaffolding. Molecules on the surface of each fiber that are capable of reacting when they come in contact with biological material like neural cells, promote the growth of neurons through and around the scaffolding. "In order to find ways or strategies to re-grow the spinal cord, we need to be able to give cells the right instructions," says Stupp. "We are able to induce neural cells to become neurons, instead of becoming another type of cell of the central nervous system."

When Stupp's team observes the growth of neurons on their scaffold through a microscope, Silva says the neurons they are looking for show as green areas, whereas a less desirable type of neural cell appears as red spots.

As they reported in the journal Science, the researchers were surprised by how much green they saw?in short, many new neurons they have been able to grow. That could mean hope for Reeve, Di Scipio and others like them, who one day may be able to leave their wheelchairs permanently.
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Wednesday, June 09, 2004

Long road ahead for stem cell initiative

Proposal to finance research qualifies for state ballot

A $3 billion state proposition to promote controversial stem cell research in California qualified Thursday for the November ballot, opening what promises to be a bruising campaign that pits moral critics of the research against family members of people with incurable diseases.

The ballot initiative represents an ambitious attempt to circumvent President Bush's stem cell policy, which severely restricts research in the field. Even so, some promoters of the research say state funding would set a dangerous precedent in departing from the system of federally financed biomedical research.

Supporters of the "California Stem Cell Research and Cures Initiative" said they turned in about 1.1 million signatures to California Secretary of State Kevin Shelley, almost twice the minimum needed to put the measure before state voters in the presidential election on Nov. 2.

The measure, which requires a simple majority to pass, would authorize an average $295 million a year in state-backed bonds to be issued over 10 years. Although the bonds would be guaranteed by tax revenue, no payments would be due for the first five years.

The ballot measure would require all the state-backed research grants to stay within California, funneled to researchers through a new institute that would be set up to weigh proposals. Backers say it is designed to be self- financing and would require no new taxes.

The initiative is backed by prominent scientists and research institutions, including UCSF and Stanford University Nobel laureates, as well as about 40 disease and patient-advocacy groups. Opponents include the Catholic Church and other moral critics, along with some liberal groups that argue the price tag is far too high.

The debate is being watched around the world by researchers anxious to see the stem cell field take off -- if a stable home and financing can be found for it.

Peter Van Etten, head of the Juvenile Diabetes Research Foundation in New York, which provided a $500,000 grant to the initiative campaign, likened the proposition to a biological Manhattan Project.

"The California initiative is an extraordinary undertaking," he said. "If it becomes law, it could significantly accelerate research in many different areas of this field. Certainly it will put a significant amount of money to work in a very focused way."

Supporters say the ballot measure would put California in the front ranks of one of the most promising new fields in medicine, generating jobs and tax revenue even before the research pays off in terms of new treatments for such diseases as diabetes, Parkinson's and spinal cord injury.

The payoff in reduced medical costs would more than cover the cost of the investment, assuming the research produces results as hoped.

"California would clearly become the world leader in curing chronic disease and injury," said Robert Klein, a Silicon Valley real estate developer who serves as state co-chair of the initiative campaign.

California is "the only place in the world that can carry this off," he said, citing the state's large number of biotech enterprises and research institutions, which are expected to provide the bulk of the scientific talent.

But critics say the state can't afford to gamble on an unproven technology that has yet to cure anything. They also contend the measure will divert resources from other health-related programs with more immediate payoffs.

Stem cells are the progenitors of all the cell types that make up the body. Although stem cells can be found in nearly all adult tissues, the debate focuses largely on stem cells derived from early-stage human embryos left over from in-vitro fertilization procedures.

The embryonic stem cells are considered by many scientists to be particularly important for researching basic human biology. The cells also may become building materials, potentially, for transplant organs or for repairing damaged spinal cords and other severe injuries.

Despite that promise, the research is considered morally objectionable by some critics because the embryos must be destroyed to obtain the stem cells.

"You can't take a stem cell out of an embryo without killing it, and the embryo is the earliest form of human life," said Carol Hogan, communications director of the California Catholic Conference in Sacramento, a lobbying and public-policy arm of the state's Catholic archdioceses.

Backers counter that the early-stage embryos involved in the research would be destroyed anyway because they are left over from in-vitro fertilization.

The measure also would specifically ban any research involving the cloning of human babies, although certain other forms of "therapeutic cloning" -- such as to create stem cells genetically customized for a particular patient -- would be allowed.

Economic arguments also promise to figure prominently in the campaign.

State Treasurer Phil Angelides and Controller Steve Westly both issued statements Thursday endorsing the initiative. They portrayed the ballot measure as an investment in California's economic future, akin to past investments in public education and transportation systems.

"To grow an economy, and to solve health problems, you have to be willing to step up and make investments," Angelides said during a telephone interview. "This investment is in the best tradition of California."

The state already has a law on the books promoting California as a safe haven for stem cell researchers. That was done to counter limits set at the federal level.

In 2001, the Bush administration sharply limited federally financed research to stem cells created before August of that year -- an effort designed to allow the field to move forward without financing the destruction of any more embryos. But researchers say there are too few federally sanctioned stem cell lines available. Now, scientists and members of Congress are pushing the White House to relax the policy. The California initiative backers say the state measure would still be needed, even if Bush relents or Democrat John Kerry, a stem cell supporter, wins in November.

A few other states, including New Jersey, have taken pro-stem cell positions with a promise of public financing. But none has moved as aggressively as the stem cell supporters in California to pay for the research.

Religious conservatives have made no secret of their opposition. The state's Catholic bishops voted to oppose the ballot measure during their spring meeting, and a coalition of stem cell critics is forming in the state to derail the measure.

"The people promoting this are manipulating victims of chronic diseases and spinal cord injury and other injuries into believing the cure is just around the corner, and that is absolutely not true," Hogan said.

Marcy Darnovsky, associate director of the Center for Genetics and Society, an Oakland group that advocates women's right to choose, also criticized the initiative Thursday, largely on practical grounds.

She disputed claims of a net benefit to the state from jobs and royalties generated in state-backed research centers. "That's a wish," she said. "We don't see any evidence to support that."

By: Carl T. Hall, Chronicle Science Writer
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New hope for spinal injury sufferers

Scientists at Glasgow University are working on a treatment to rebuild the damaged spinal cords of people paralysed by spinal injuries - by using cells taken from the patient's own nose.

The researchers have been given a 322,000 grant by the Medical Research Council to develop studies which could help patients "rebuild" the nerve circuits in their spinal cords.

This could help to restore some feeling and control to paralysed limbs and organs.

And they hope the same approach could also help people with other diseases of the nervous system like multiple sclerosis.

Neuroscientists Dr Susan Barnett and Dr John Riddell plan to use stem cells from a special layer of tissue in the lining of the nose to "plug the gap" left when a spinal cord is damaged.

The cells then create a framework through which the nerves in the spinal cord can regenerate.

The nerves in the nose which provide the sense of smell are unique because they continually regenerate, unlike nerves in the spinal cord and other areas of the brain.

Previous studies by the Glasgow group and others have shown the olfactory cells in the lining of the nose can partially correct some models of spinal cord injury by promoting the growth of nerves.

But Dr Barnett warned a complete cure which would see affected people walking again through nerve regeneration was a very long way off.
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Nasal cells key to paralysis cure

Researcers are developing a method of transplanting nose cells into the spinal cord of paralysed patients to help them walk again.

The ground-breaking Scottish research aims to renew the lost connections between the brain and muscles that give us our movement and sense of touch. If successful, the tests at Glasgow university could provide hope for the 35,000 people in the UK who have a spinal cord injury.

The research team is focusing its study on stem cells in the nose, which provide the sense of smell. They believe these cells from the olfactory system could be key in reconnecting signals in the spinal cord as they constantly regenerate over a person?s lifetime.

The crucial factor blocking patients suffering from complete spinal cord injuries from regaining movement has been the area?s inability to regenerate itself.

Dr Sue Barnett, a cell biologist who is co-director of the project, said: "The basic idea of our research is to take cells from the part of the nervous system that gives us our sense of smell and to put these in the spinal cord. We want to transplant them into the spinal cord injury to create an environment that will be favourable to the regeneration of the injured nerves."

"Our work so far gives us good reason to believe that we can make the stem cells from the nose become the sorts of cells which are needed to support repair of the damaged spinal cord."

"If successful in promoting regeneration, this approach could provide a feasible treatment because it is possible to take cells from the lining of the nose without any permanent effect on the sense of smell."

Research with stem cells has attracted international controversy, in particular research conducted on embryos. Although banned in the US, it is one method being considered for use by researchers to help rebuild the circuits of the spinal cord.

However, one vocal supporter of pioneering stem cell research is Christopher Reeve, the Superman actor paralysed after a riding accident in 1995. He could benefit if the three-year study is a success. Reeve has called for the method to be used for researching treatments for spinal injury patients in the US.

Dr John Riddell, a spinal cord neuroscientist - who is also directing the 322,000 project - said the study also had the potential to help people with other diseases of the nervous system, such as multiple sclerosis.

He added: "It's a very exciting area and there has been a great deal of progress in recent years. Not so long ago, it was thought impossible to achieve any regeneration in the spinal cord."

"Within the next 10 years, I think there will be some form of treatment available to allow some patients to have modest improvements in function."

By Liam McDougall
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Friday, June 04, 2004

Combination Therapy Overcomes Spinal Injuries in Rats

New research that restored significant mobility to paralyzed rats offers hope -- albeit distant hope -- to the 243,000 Americans living with spinal cord injuries, experts say.

"This is quite exciting news, certainly to people with spinal cord injuries, their families and the health-care professionals who care for them. But we have a long way to go," said Dr. Kristjan Ragnarsson, chairman of rehabilitation medicine at Mount Sinai Medical Center in New York City. "Experiments in rats don't always translate very quickly into anything in humans."

Using a novel three-step approach, scientists succeeded in restoring up to 70 percent of normal walking function to the paralyzed rats. The animals received a combination of cell transplants along with two different medications. The result: They also had better foot placement, stability while walking, and coordination of front and back legs, the researchers said.

The study was conducted at the Miami Project to Cure Paralysis, a comprehensive spinal cord injury research center at the University of Miami School of Medicine. The research appears in the June issue of Nature Medicine.

Considerable attention has been focused on trying to restore mobility in people with spinal cord injuries by regrowing nerve cells, but, so far, success has been elusive.

"It is very difficult to bridge the gap between the normal section of the spinal cord over the injured part and into the part below which is relatively normal," Ragnarsson explained. "We have suspected for a long time that the inability of neurofibers to grow across this gap is related to a very hostile terrain."

The issue of "hostile terrain" around the damaged area of the spine proved key to the new study.

"The work that transformed the field of spinal cord repair showed in 1980 that nerve cells in the central nervous system do have the capacity to regrow, but it depends upon their environment," said senior study author Mary Bartlett Bunge. She is a faculty member of the Miami Project to Cure Paralysis and a professor of cell biology and anatomy and neurological surgery at the University of Miami School of Medicine. Bunge designed the study with colleague Dr. Damien Pearse.

Bunge's group at the Miami Project had previously shown that Schwann cells from the peripheral nervous system resulted in new nerve fibers when transplanted to the spinal cord.

"Schwann cells are formed into a cable that acts as a bridge to span the injury site. The bridge provides a supportive and growth-promoting scaffold for the regrowth of nerve fibers," Bunge explained. "The nerve fibers grew on to the bridge [of animals in the 1980 study], but they did not leave it to grow into the spinal cord in the appropriate location."

Other researchers have since discovered that the reason for this lack of growth may have been inadequately low levels of a "messenger molecule" called cyclic adenosine monophosphate (cAMP). Levels of cAMP dropped precipitously in the rats in the new study immediately after they were injured.

For the new study, the researchers first injured rats in the thoracic region of the spinal cord, which resulted in paralysis to the legs. Bruising is the most common form of spinal cord injury among people. An estimated 10,000 Americans suffer such injuries every year.

For two weeks, Bunge and her colleagues injected rolipram, which has been used as an antidepressant in humans and in clinical trials for multiple sclerosis. "The administration of rolipram prevents that initial drop in cAMP," Bunge said.

One week after the injury, the researchers transplanted by injection 2 million Schwann cells into the bruised area of each rat's spinal cord and, at the same time, injected cAMP into the areas above and below the transplant area. The rolipram prevented the breakdown of cAMP so it could accumulate in the animals. The levels of cAMP rose with the triple combination treatment, the researchers said.

The result was an impressive restoration in the ability of the animals to walk.

"This is the best strategy that we have found so far, the best result I have seen in 15 years of very hard work," Bunge said. "I think a combination strategy is gong to be very important because the reactions in spinal cord tissue after injury are many and varied, and therefore there are many issues to be considered and addressed in designing an effective strategy."

While it's too soon for human application, the new research contains some promising aspects.

"In all our work we try to conduct our experiments in a relevant way to human spinal cord injury," Bunge said. "For example, the Schwann cells we transplant are always from an adult animal, comparable to using an injured person's own Schwann cells."

The next steps involve replicating the study in different animals and understanding what amounts of rolipram and cAMP are most effective and when they should be given for optimal results.

In the meantime, a one-step approach might help. "We have quite a bit of preparatory work to do before going to a clinical trial, but I think it may be possible to use rolipram by itself because we did see a good effect with rolipram alone," Bunge said. "I want to be cautious, though. I don't want people in a wheelchair to say I'm going down there [Miami] next week. We have to be very well prepared so that we don't do more damage than good."

By Amanda Gardner - HealthDay Reporter (HealthDayNews)
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Hope for spinal cord injuries

(New York) - Travis Roy was a promising hockey player, but during the first few seconds of his first college game in 1995 a freak crash left him paralyzed.

Roy has since become an advocate for paralyzed people, and he is excited about the latest study, even though it is only in rats, "I have hope, and that's a wonderful thing to have in this condition."

The research was carried out at the Miami Project to Cure Paralysis, set up by football Hall of Famer Nick Buoniconti after his son, Marc, was paralyzed in a college football game.

Dr. Mary Bunge and her team used a combination of nerve cell therapy and drugs to restore leg movement in rats that had been paralyzed with a laboratory-inflicted spine injury, "This is the most important work to come out of my laboratory in the 15 years that I have been in the Miami project."

The research starts with the observation that nerves in limbs such as the finger can re-grow if they are injured, something that doesn't happen with nerves in the spine. So, the scientists set to change the conditions in the spine to allow injured nerves to re-grow.

They accomplished it by transplanting nerves that do regenerate into the spines of the rats. They were able to keep the nerves growing with a natural body chemical called cAMP and a drug called Rolipram, and the rats were able to walk again.

The research is still years from helping human patients, but it provides hope for the quarter million Americans who live with spinal cord injuries that the condition will someday be reversed.
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Old drug has new potential

EPO: A popular medicine for anemics holds promise for a range of other conditions, including stroke, heart attack and spinal cord injury.
By David Kohn - Sun Staff

In 1987, neurologist Hannelore Ehrenreich noticed something odd in anemic patents being treated with a drug called erythropoietin. After taking the drug for just a few days, they seemed mentally sharper and more alert.

After several years studying the drug's effect on brain cells, she had an inspiration: Maybe the anemia drug could also heal brain damage caused by strokes.

Among colleagues, her theory was not a hit. "People laughed at me. They said I was crazy," remembers Ehrenreich, a researcher at the University of Gottingen in Germany. But 12 years later, her notion looks increasingly prophetic.

Erythropoietin, known as EPO, is showing promise not only for stroke, but also for a wide range of ailments including heart attack, multiple sclerosis, spinal cord injury, and nerve and intestinal problems. Some researchers think it could even prove helpful with schizophrenia and Alzheimer's disease.

EPO (pronounced EE-poe) seems to protect a variety of organs and tissues from harm, including the heart, the brain and nervous system.

"We're very excited about it because it has widespread and very potent activity," said neuroscientist Michael Brines, director of research at Warren Pharmaceuticals. The company is looking at EPO's ability to heal spinal cord and cardiac damage. Animals treated with the drug show "remarkable" recovery, Brines said.

EPO has been around for millions of years; it exists in a wide range of animals, including fish and humans. Three decades ago, in one of the first feats of genetic engineering, scientists created a synthetic version of the substance.

Since then, artificial EPO has become a popular medicine for increasing red blood cell levels in anemics. Because boosting these cells increases the amount of oxygen available to muscles and lungs, the drug has also been used by elite endurance athletes looking for an unfair advantage. Many national and international sports organizations have banned its use.

But in the past four years, researchers have realized that EPO can do much more. "It has a lot of potential in terms of preventing tissue death," said Johns Hopkins University cardiologist Gregg Semenza, who is studying EPO's effect on the heart. In studies of rats, it significantly decreased heart attack damage.

High hopes

Another Johns Hopkins cardiologist, Joshua Hare, is studying EPO in pigs, whose hearts more closely resemble humans'. The data isn't in yet, but based on others' work and his own rat study, Hare has high hopes.

"It could greatly reduce the size of a heart attack, and the amount of damage," he said.

Surprisingly, some researchers say the two companies that make EPO seem less than enthusiastic about the drug's possible new uses. They accuse the companies, Amgen and Ortho Biotech, of showing little interest in funding new EPO research - possibly because new studies could uncover side effects that would endanger the drug's multibillion-dollar sales as an anemia drug. Both companies deny that.

Another possible reason for this alleged indifference: Recent studies looking at EPO as a cancer treatment found evidence that the drug may harm those patients.

Ironically, it is EPO's status as an approved drug that excites many researchers. Because it has been widely used for decades, researchers and regulators already know that it is relatively safe. "The beauty of EPO is that it's really well tolerated," said Ehrenreich, who is studying the drug as a stroke treatment.

She has found that patients given EPO injections within eight hours of a stroke did significantly better than those given a placebo. The EPO group had less brain damage and retained more functional ability: Only 14 percent ended up in nursing homes, compared with about half the placebo patients.

Ehrenreich recently started a larger study, which will examine more than 500 patients. If that trial goes well, EPO has a good chance of being approved in Germany, and perhaps the European Union, as a stroke treatment, she said.

In stroke and heart attack, EPO seems to work via the same mechanism, by blocking a process known as programmed cell death.

After many kinds of injury, cells around the damaged area destroy themselves in a misguided effort to promote healing. Ironically, this secondary suicide, called apoptosis, often causes more damage than the original injury. Somehow, Semenza says, EPO shuts off the cellular and genetic signals that trigger cell death.

Scientists have had little success in finding ways to stop apoptosis in humans. If EPO can do this, it would be a "huge deal, a new approach to tissue damage in general," says Hare.

Another promising area is spinal cord injury, which also involves programmed cell death. An Italian researcher reported that in rats with spinal cord injury, the drug markedly improved recovery. "It was one of the best effects we've ever seen," said University of Miami neuroscientist Dalton Dietrich, who is finishing a similar study funded by the National Institutes of Health. If the results of that study are positive, he likely will do a small human study next.

Protector of nerves

Even beyond blocking cell death, EPO seems to be a powerful protector of nerves, and researchers are studying it for use in patients with other neurological disorders. Johns Hopkins neurologists Sanjay Keswani and Ahmet Hoke are beginning an EPO study of people with transverse myelitis, an autoimmune disorder that damages the nervous system and often leads to paralysis.

Keswani believes the drug could treat a wide range of neurological diseases, including multiple sclerosis, a progressive paralysis that afflicts more than 350,000 Americans. "Any neurodegenerative disease, it's got potential," he said.

Others think EPO could be used to treat some chronic brain diseases. Ehrenreich, for example, is trying EPO on a group of 40 schizophrenics. In that illness, the cortex (the brain region responsible for logical thinking) gradually shrinks. EPO may thwart this neuronal loss, Ehrenreich says.

Neuroscientist Stuart Lipton is studying EPO's effect on HIV-related brain damage. In many cases, the disease causes mental problems, often to the point of a full-scale dementia resembling Alzheimer's.

Lipton, director of the Center for Neuroscience and Aging Research at the Burnham Institute in San Diego, says the early results look promising. He and others suspect that EPO could also be used to stave off Alzheimer's disease, the mysterious ailment that progressively kills neurons throughout the brain.

EPO does have limitations. For one, it can't be taken orally. Because it is a large protein that is broken down in the stomach, it must be injected. More importantly, in non-anemic patients it can raise red cell levels to the point that blood thickens and clots more easily, raising the risk of heart attack or stroke.

Particularly when EPO is used over months or years, as it would be in neurodegenerative disease, this effect might pose a serious hazard, researchers say.

To get around the problem, several companies, including Warren Pharmaceuticals, are working on versions of EPO that don't raise red cell levels. Lipton is also trying to combine EPO with other drugs, allowing doctors to use the hormone at lower doses.

He and others suspect that EPO isn't the only drug that will turn out to have benefits far beyond its original purpose. Many widely used compounds likely have hidden talents just waiting to be discovered, they say.

"There's a lot of stuff going on under our noses," said Hare, the Hopkins cardiologist. "You've got to be looking for something to find it."
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