Scientists find how deadly new virus infects human cells

By Kate Kelland

LONDON (Reuters) - Scientists have worked out how a deadly new virus which was unknown in humans until last year is able to infect human cells and cause severe, potentially fatal damage to the lungs.

In one of the first detailed studies of the virus - which emerged in the Middle East and has so far infected 15 people worldwide, killing nine of them - Dutch researchers identified a cell surface protein it uses to enter and infect human cells.

The finding, published in the journal Nature, came as the World Health Organization (WHO) confirmed the 15th case of the virus, known as novel coronavirus or NCoV, in a male patient in Saudi Arabia who died on March 2.

Other cases have been in Jordan and Qatar, and in patients in Germany and Britain linked to travel in the Middle East.

NCoV is from the same family of viruses as those that cause common colds and the one that caused the deadly outbreak of Severe Acute Respiratory Syndrome (SARS) that first emerged in Asia in 2003.

The WHO first issued an international alert about it in September after it was identified in a Qatari man in Britain who had recently been in Saudi Arabia.

A study published last month found that NCoV was well adapted to infecting human cells and may be treatable with medicines similar to the ones used for SARS, which killed a tenth of the 8,000 people it infected.

In this latest study, led by Bart Haagmans at the Erasmus Medical Center in The Netherlands, researchers set out to find how the virus got into cells - which receptors it used - and then to find out where in the body those receptors were common.

POTENTIAL VACCINES

"Once you can identify the receptor and you know the distribution of the receptor in the body, then you can get more information on the pathogenesis (the way it infects people) of the virus and the possibility for transmission," Haagmans said in a telephone interview.

Researchers identified the key receptor for the disease as a cell surface protein called dipeptidyl peptidase 4 (DPP4).

They also found cells containing DPP4 receptors were common in the lower respiratory tract but not in the upper respiratory tract - giving clues to why the virus causes illness in the lungs rather than in the nose and throat as a cold virus would.

The findings should help researchers find ways of developing potential drugs or vaccines to block the DPP4 receptors and prevent infection, Haagmans said.

A few drugs that block DPP4 receptors are already on the market, licensed for use in diabetes, but Haagmans said his team already tried using those to stop the virus in laboratory tests and found they did not work.

He said, however, that the team was working with other molecules that might block the receptors and could form the basis for developing a potential vaccine.

Initial analysis by scientists at Britain's Health Protection Agency last year found that NCoV's closest relatives were most probably bat viruses.

Yet further work by a research team in Germany suggests NCoV may have come through an intermediary - possibly goats.

Haagmans said since DPP4 receptors were also present in other species, including bats, his findings showed it was feasible the virus came from bats. He said the idea that goats may have been an intermediary also looked feasible.

(Reporting by Kate Kelland; Editing by Pravin Char)

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New stem cell method makes functioning liver cells

By Kate Kelland

LONDON | Wed Oct 12, 2011 3:57pm EDT

LONDON (Reuters) - British scientists have developed a new stem cell technique for growing working liver cells which could eventually avoid the need for costly and risky liver transplants.

A team of researchers led by the Sanger Institute and the University of Cambridge used cutting-edge methods to correct a genetic mutation in stem cells derived from a patient's skin biopsy, and then grew them into fresh liver cells.

By putting the new liver cells into mice, they showed they were fully functioning.

"We have developed new systems to target genes and ... correct ... defects in patient cells," said Allan Bradley, director of the Sanger Institute.

At a briefing about the work, Bradley said the technique -- the first success of its kind -- leaves behind no trace of the genetic manipulation, except for the gene correction.

"These are early steps, but if this technology can be taken into treatment, it will offer great possible benefits for patients," he added.

Stem cells are the body's master cells, the source for all other cells. Scientists say they could transform medicine, providing treatments for blindness, spinal cord and other severe injuries, and new cells for damaged organs.

Research is focused on two main forms -- embryonic stem cells, which are harvested from embryos, and reprogrammed cells, also known as induced pluripotent stem cells or iPS cells, which are reprogrammed from ordinary skin or blood cells.

When they were first discovered in 2006, iPS cells looked like a perfect solution to the ethical debate over the use of embryonic stem cells because they are made in a lab from ordinary skin or blood cells. Embryonic stem cells are usually harvested from leftover embryos at fertility clinics and their use is opposed by many religious groups.

But in recent years, concerns have been raised that iPS cells may not be as "clean" or as capable as embryonic cells.

Last year, a group led by Robert Lanza, of the U.S. firm Advanced Cell Technology, compared batches of iPS cells with embryonic stem cells and noticed the iPS cells died more quickly and were much less able to grow and expand.

CORRECTING MUTATION

In Wednesday's study, published in the journal Nature, the British team took skin cells from a patient with a mutation in a gene called alpha1-antitrypsin, which is responsible for making a protein that protects against inflammation.

People with mutant alpha1-antitrypsin are not able to release the protein properly from the liver, so it becomes trapped there and eventually leads to liver cirrhosis and lung emphysema. This is one of the most common inherited liver and lung disorders and affects about one in 2,000 people of North European origin, the researchers said.

Having harvested the skin cells, the scientists reprogrammed them back into stem cells and then used a type of "molecular scissor" technique known as a zinc finger nuclease to snip the cells' genome at precisely the right place and insert a correct version of the gene using a DNA transporter called piggyBac.

The leftover piggyBac sequences were then removed from the cells, cleaning them up and allowing them to be converted into liver cells without any trace of residual DNA damage at the site of the genetic correction.

"We then turned those cells into human liver cells and put them in a mouse and showed that they were viable," David Lomas, a Cambridge professor of respiratory biology who also worked on the team, told reporters at the briefing.

Ludovic Vallier, also from Cambridge University, said the results were a first step toward personalized cell therapy for genetic liver disorders. "We still have major challenges to overcome...but we now have the tools necessary," he said.

The researchers said it could be another five to 10 years before full clinical trials of the technique could be run using patients with liver disease. But if they succeed, liver transplants -- costly and complicated procedures where patients need a lifetime of drugs to ensure the new organ is not rejected -- could become a thing of the past.

"If we can use a patient's own skins cells to produce liver cells that we can put back into the patient, we may prevent the future need for transplantation," said Lomas.

(Additional reporting by Simon Roach; Editing by Tim Pearce)

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Stem cells reverse blindness caused by chemical burns

By Alicia Chang, Associated PressLOS ANGELES — Dozens of people who were blinded or otherwise suffered severe eye damage when they were splashed with caustic chemicals had their sight restored with transplants of their own stem cells — a stunning success for the burgeoning cell-therapy field, Italian researchers reported Wednesday.The treatment worked completely in 82 of 107 eyes and partially in 14 others, with benefits lasting up to a decade so far. One man whose eyes were severely damaged more than 60 years ago now has near-normal vision.

"This is a roaring success," said ophthalmologist Dr. Ivan Schwab of the University of California, Davis, who had no role in the study — the longest and largest of its kind.

Stem cell transplants offer hope to the thousands of people worldwide every year who suffer chemical burns on their corneas from heavy-duty cleansers or other substances at work or at home.

The approach would not help people with damage to the optic nerve or macular degeneration, which involves the retina. Nor would it work in people who are completely blind in both eyes, because doctors need at least some healthy tissue that they can transplant.

In the study, published online by the New England Journal of Medicine, researchers took a small number of stem cells from a patient's healthy eye, multiplied them in the lab and placed them into the burned eye, where they were able to grow new corneal tissue to replace what had been damaged. Since the stem cells are from their own bodies, the patients do not need to take anti-rejection drugs.

Adult stem cells have been used for decades to cure blood cancers such as leukemia and diseases like sickle cell anemia. But fixing a problem like damaged eyes is a relatively new use.

Researchers have been studying cell therapy for a host of other diseases, including diabetes and heart failure, with limited success.

Adult stem cells, which are found around the body, are different from embryonic stem cells, which come from human embryos and have stirred ethical concerns because removing the cells requires destroying the embryos.

Currently, people with eye burns can get an artificial cornea, a procedure that carries such complications as infection and glaucoma, or they can receive a transplant using stem cells from a cadaver, but that requires taking drugs to prevent rejection.

The Italian study involved 106 patients treated between 1998 and 2007. Most had extensive damage in one eye, and some had such limited vision that they could only sense light, count fingers or perceive hand motions. Many had been blind for years and had unsuccessful operations to restore their vision.

The cells were taken from the limbus, the rim around the cornea, the clear window that covers the colored part of the eye. In a normal eye, stem cells in the limbus are like factories, churning out new cells to replace dead corneal cells. When an injury kills off the stem cells, scar tissue forms over the cornea, clouding vision and causing blindness.

In the Italian study, the doctors removed scar tissue over the cornea and glued the laboratory-grown stem cells over the injured eye. In cases where both eyes were damaged by burns, cells were taken from an unaffected part of the limbus.

Researchers followed the patients for an average of three years and some as long as a decade. More than three-quarters regained sight after the transplant. An additional 13% were considered a partial success. Though their vision improved, they still had some cloudiness in the cornea.

Patients with superficial damage were able to see within one to two months. Those with more extensive injuries took several months longer.

"They were incredibly happy. Some said it was a miracle," said one of the study leaders, Graziella Pellegrini of the University of Modena's Center for Regenerative Medicine in Italy. "It was not a miracle. It was simply a technique."

The study was partly funded by the Italian government.

Researchers in the United States have been testing a different way to use self-supplied stem cells, but that work is preliminary.

One of the successful transplants in the Italian study involved a man who had severe damage in both eyes as a result of a chemical burn in 1948. Doctors grafted stem cells from a small section of his left eye to both eyes. His vision is now close to normal.

In 2008, there were 2,850 work-related chemical burns to the eyes in the United States, according to the Bureau of Labor Statistics.

Schwab of UC Davis said stem cell transplants would not help those blinded by burns in both eyes because doctors need stem cells to do the procedure.

"I don't want to give the false hope that this will answer their prayers," he said.

Dr. Sophie Deng, a cornea expert at the UCLA's Jules Stein Eye Institute, said the biggest advantage was that the Italian doctors were able to expand the number of stem cells in the lab. This technique is less invasive than taking a large tissue sample from the eye and lowers the chance of an eye injury.

"The key is whether you can find a good stem cell population and expand it," she said.

Copyright 2010 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed. Guidelines: You share in the USA TODAY community, so please keep your comments smart and civil. Don't attack other readers personally, and keep your language decent. Use the "Report Abuse" button to make a difference. Read more.

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Stem cells reverse blindness caused by chemical burns

By Alicia Chang, Associated PressLOS ANGELES — Dozens of people who were blinded or otherwise suffered severe eye damage when they were splashed with caustic chemicals had their sight restored with transplants of their own stem cells — a stunning success for the burgeoning cell-therapy field, Italian researchers reported Wednesday.The treatment worked completely in 82 of 107 eyes and partially in 14 others, with benefits lasting up to a decade so far. One man whose eyes were severely damaged more than 60 years ago now has near-normal vision.

"This is a roaring success," said ophthalmologist Dr. Ivan Schwab of the University of California, Davis, who had no role in the study — the longest and largest of its kind.

Stem cell transplants offer hope to the thousands of people worldwide every year who suffer chemical burns on their corneas from heavy-duty cleansers or other substances at work or at home.

The approach would not help people with damage to the optic nerve or macular degeneration, which involves the retina. Nor would it work in people who are completely blind in both eyes, because doctors need at least some healthy tissue that they can transplant.

In the study, published online by the New England Journal of Medicine, researchers took a small number of stem cells from a patient's healthy eye, multiplied them in the lab and placed them into the burned eye, where they were able to grow new corneal tissue to replace what had been damaged. Since the stem cells are from their own bodies, the patients do not need to take anti-rejection drugs.

Adult stem cells have been used for decades to cure blood cancers such as leukemia and diseases like sickle cell anemia. But fixing a problem like damaged eyes is a relatively new use.

Researchers have been studying cell therapy for a host of other diseases, including diabetes and heart failure, with limited success.

Adult stem cells, which are found around the body, are different from embryonic stem cells, which come from human embryos and have stirred ethical concerns because removing the cells requires destroying the embryos.

Currently, people with eye burns can get an artificial cornea, a procedure that carries such complications as infection and glaucoma, or they can receive a transplant using stem cells from a cadaver, but that requires taking drugs to prevent rejection.

The Italian study involved 106 patients treated between 1998 and 2007. Most had extensive damage in one eye, and some had such limited vision that they could only sense light, count fingers or perceive hand motions. Many had been blind for years and had unsuccessful operations to restore their vision.

The cells were taken from the limbus, the rim around the cornea, the clear window that covers the colored part of the eye. In a normal eye, stem cells in the limbus are like factories, churning out new cells to replace dead corneal cells. When an injury kills off the stem cells, scar tissue forms over the cornea, clouding vision and causing blindness.

In the Italian study, the doctors removed scar tissue over the cornea and glued the laboratory-grown stem cells over the injured eye. In cases where both eyes were damaged by burns, cells were taken from an unaffected part of the limbus.

Researchers followed the patients for an average of three years and some as long as a decade. More than three-quarters regained sight after the transplant. An additional 13% were considered a partial success. Though their vision improved, they still had some cloudiness in the cornea.

Patients with superficial damage were able to see within one to two months. Those with more extensive injuries took several months longer.

"They were incredibly happy. Some said it was a miracle," said one of the study leaders, Graziella Pellegrini of the University of Modena's Center for Regenerative Medicine in Italy. "It was not a miracle. It was simply a technique."

The study was partly funded by the Italian government.

Researchers in the United States have been testing a different way to use self-supplied stem cells, but that work is preliminary.

One of the successful transplants in the Italian study involved a man who had severe damage in both eyes as a result of a chemical burn in 1948. Doctors grafted stem cells from a small section of his left eye to both eyes. His vision is now close to normal.

In 2008, there were 2,850 work-related chemical burns to the eyes in the United States, according to the Bureau of Labor Statistics.

Schwab of UC Davis said stem cell transplants would not help those blinded by burns in both eyes because doctors need stem cells to do the procedure.

"I don't want to give the false hope that this will answer their prayers," he said.

Dr. Sophie Deng, a cornea expert at the UCLA's Jules Stein Eye Institute, said the biggest advantage was that the Italian doctors were able to expand the number of stem cells in the lab. This technique is less invasive than taking a large tissue sample from the eye and lowers the chance of an eye injury.

"The key is whether you can find a good stem cell population and expand it," she said.

Copyright 2010 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed. Guidelines: You share in the USA TODAY community, so please keep your comments smart and civil. Don't attack other readers personally, and keep your language decent. Use the "Report Abuse" button to make a difference. Read more.

View the original article here