ANALYSIS-Gene therapy edges towards commercial reality

February 27, 2009

Reuters
ANALYSIS-Gene therapy edges towards commercial reality
02.27.09, 5:46 AM ET

United Kingdom –

* Gene therapy advances after troubled history

* Ark’s Cerepro may be first gene medicine in Europe or U.S.

* More than 1,470 gene therapy trials since 1989

By Ben Hirschler, European Pharmaceuticals Correspondent

LONDON, Feb 27 (Reuters) – Gene therapy may be about to become a commercial reality, 20 years after the first experiments with the ground-breaking medical technology.

But the tale of two biotech companies — one British and one U.S. — suggests a tricky road ahead.

On the one side, French authorities last week allowed an experimental gene medicine from Britain’s Ark Therapeutics to be prescribed to certain patients with brain cancer, even though it is not approved for general use.

The news boosted hopes that the European Medicines Agency will clear Ark’s drug Cerepro for sale across the European Union in the second half of 2009.

By contrast, U.S.-based Introgen Therapeutics — which had been competing to get the first gene therapy approved in Western markets — filed for bankruptcy in December, after a regulatory setback for its experimental cancer drug Advexin.

The last two decades have seen more than 1,470 clinical trials involving gene therapy, two-thirds of them aimed at cancer, according to the Journal of Gene Medicine.

But the only drug to get to market so far has been one for for head and neck cancer from Shenzhen SiBiono GeneTech, which was approved in China in 2003 on data that most analysts do not believe would have supported a Western green light.

Some of the other U.S. and European companies in the space include Genzyme, Targeted Genetics, GenVec, Neurologix, Amsterdam Molecular Therapeutics and Oxford BioMedica.

BUBBLE BOY DISEASE

The idea of using genes to treat disease gained credibility in 1990, when the world’s first clinical tests showed early success against a rare condition caused by faulty genes, called severe combined immunodeficiency (SCID).

People with SCID — also known as “bubble boy disease” — cannot cope with infections and usually die in childhood.

The field then suffered a major setback when an Arizona teenager died in a gene therapy experiment in 1999 gene and two French boys with SCID developed leukaemia in 2002.

More recently, though, doctors have made encouraging advances.

Last year, two separate academic teams reported success in using gene therapy for a type of inherited blindness call Leber congenital amaurosis.

And last month an extended follow-up study of SCID children concluded that eight of 10 treated seemed to have been cured, leading the New England Journal of Medicine to declare that gene therapy was “fulfilling its promise”.

“There have been setbacks but we are finally making progress,” Thierry VandenDriessche, president of the European Society of Gene and Cell Therapy, told Reuters.

“The tools to deliver genes into cells have been perfected and have become safer and more efficient and we are starting to see the fruits of this in the clinic.”

NEW BRANCH OF MEDICINE

Nigel Parker, chief executive of Ark, believes his company is ahead in what will become a major new branch of medicine. He plays down past setbacks as inevitable learning points for any new technology.

“If you think how long it takes for a new therapeutic idea to come to market, it does take about 20 years. So this is not too far away from the normal pharmaceutical cycle,” he said.

Industry analysts are still divided as to how commercially successful Cerepro and other gene-based medicines will be.

“We’re definitely closer but we are still not quite there yet,” said Nomura Code analyst Samir Devani, who forecasts peak worldwide sales for Cerepro of $250 million a year.

Paul Cuddon of KBC is more sceptical about the drug’s prospects, pending the release of full Phase III trial data.

One of the big hurdles for gene therapy has always been how to get therapeutic genes to the right part of the body.

Normally, a virus is used as a carrier. But viruses can trigger serious immune reactions and damaging genetic mutations, if they integrate into the wrong part of the genome. They are also difficult to steer, making it hard to ensure that genes get to the right places in the body. One option is to adopt a more localised approach.

In the case of blindness, a common cold virus is used to deliver a corrective gene directly into the eyes of patients.

Cerepro, meanwhile, works via injections into the brain that transmit a gene for making a protein, which then reacts with an antiviral drug to produce a chemical that kills cancer cells. That makes Ark’s drug a temporary and local treatment.

“If Cerepro gets approved fully for European use, I don’t think that changes the risk profile for any other gene therapy because these products are so specific,” said Piper Jaffray analyst Sam Fazeli. (Editing by David Holmes)

link back url: http://www.forbes.com/feeds/reuters/2009/02/27/2009-02-27T104603Z_01_LQ661216_RTRIDST_0_HEALTH-GENETHERAPY-ANALYSIS.html


Boy in bubble’ story not forgotten 25 years after death

February 22, 2009

Boy in bubble’ story not forgotten 25 years after death

By TODD ACKERMAN Copyright 2009 Houston Chronicle

Feb. 21, 2009, 9:07PM

It was a story that touched the world, the cute little boy who lived virtually his whole life inside a series of sterile plastic bubbles, waiting for a cure for his fatal immune disease that, tragically, never came.

Known as “the boy in the bubble,” or just David, he was the Texas Medical Center’s most famous patient from the early ’70s to the mid-’80s. As a captivated public watched, he grew up isolated from both germs and human touch before finally dying, at age 12, after the failure of a then experimental bone-marrow transplant.

The case was truly unique: Never again would a child live a life in such a cocoon. “It’s such a great human interest story, how so many people came to care about him,” says James Jones, a former University of Houston historian and author of a forthcoming book on the subject. “Most medical stories have a flash-in-the pan quality, but David’s story didn’t go away. For 12 years, thanks to news coverage around his birthday, he captured hearts worldwide.”

Today, 25 years to the day since his death, David Phillip Vetter remains one of Houston’s signature stories, his mark still felt in a legacy of vexing ethical questions and medical advances.

The ethical questions involve David’s role as a sort of living experiment. While keeping him alive was largely seen as a technological triumph and a valiant effort that gave him and his family 12 years together, some bioethicists argue it was a classic example of doctors promising more than medicine could deliver and creating an unacceptable quality of life. That quality took a toll on David’s emotional well-being.

David’s medical legacy is less open to debate. Doctors say he contributed enormously to a better understanding of clinical immunology, an understanding that has resulted in better treatment for many diseases involving the immune system.

At a time when HIV/AIDS was coming onto the scene, David also put diseases of the immune system on people’s radar screen.

“A lot of kids are alive today because David was here,” David J. Vetter said last week in a rare interview about his son. “Perhaps it was meant to be — that he was the little guy through whom doctors and the world were meant to learn about the immune system.”

Vetter said it was “kind of unbelievable it happened to us, plain, ordinary people.” Marveling at his family’s ability to cope, he said it was like “the whole world came crashing down” when David was diagnosed.

David had severe combined immunodeficiency (SCID), an inherited condition in which the patient lacks the white blood cells that fight infection. It afflicts 40 to 50 babies born every year in the United States and is fatal within a year or two without treatment.

In 1971, the year David was born, the only hope was a bone marrow transplant from a donor whose blood matched perfectly. The Vetters hoped their daughter would provide the match.

Sibling died in infancy

Because the Vetters knew there was a chance David would have the immune condition — a first son had died of SCID in infancy — he was delivered by cesarean section in a sterile operating room at Texas Children’s Hospital. Immediately, he was whisked into a sealed bubble intended as a stopgap measure until a match could be found.

“The Vetters were the only parents who asked if we could protect their boy,” said Dr. Mary Ann South, a pediatric immunologist and one of David’s team of doctors. “We’d treated seven or eight children with the disease and all of them died; nothing worked, and they never lived long enough for us to learn about the disease. ”

But David’s sister’s blood didn’t match. The wait for a match, or any kind of cure, dragged on.

The boy with large, dark eyes and a shock of dark hair loved Star Wars films and the Houston Oilers. He longed to drink a Coke and walk barefoot on the grass. He was a straight-A student taught by telephone.

The protective bubbles at the hospital and his parents’ home became larger and larger as he grew. Their walls were fitted with heavy-duty rubber gloves through which doctors cared for him; food was sterilized and slipped in through air locks. NASA designed a spacesuit to give him freedom to walk outside, but David didn’t take to it.

In late 1983, as David began losing hope he would ever leave the bubble, doctors told the Vetters of a promising new bone marrow transplant technique using less than perfect matches.

The transplant seemed to work well initially. But in January 1984, David began showing signs of illness and soon was removed from the bubble for treatment. When he died 15 days later of a form of lymph cancer caused by an undetected Epstein Barr virus in the transplant, it made headlines around the world.

“People often ask what’s the measure of someone’s life, but very few people stood as tall as David,” said Dr. William Shearer, a Baylor College of Medicine pediatric immunologist and David’s doctor in later years. “More than any scientist, he taught us by his life.”

Among the lessons were one of the first proofs that viruses can cause cancer. He also was the source of DNA that helped identify the gene that causes immune deficiencies, a discovery that led to a test for the disease in newborns, when it is most effectively treated.

Debate continues

A recent study found that bone marrow transplants, even imperfectly matched ones, work 90 percent of the time if performed within three months of birth.

Still, the debate about the ethics of David’s treatment continues. Bruce Jennings, director of the Center for Humans and Nature, said it shows the need to be careful about the faith placed in technology and the temptation to treat children as guinea pigs. But University of Texas Medical Branch at Galveston ethicist William Winslade said harsh criticism isn’t appropriate “at a time when people were doing everything they could to save lives.”

If anything seems certain, it is that David will not easily be forgotten. He has been celebrated in dramatic works, music and sculpture.

A center at Texas Children’s and a school and street in The Woodlands bear his name. And as historian Jones notes, the term bubble has become an enduring part of the language, a parent’s shorthand for the thing they wish they could put their children in to keep them out of harm’s way.

Still, David’s best epitaph may be the one on his gravestone in Conroe.

“He never touched the world,” says the epitaph. “But the world was touched by him.”

todd.ackerman@chron.com

linkback url http://www.chron.com/disp/story.mpl/front/6274796.html


‘Bubble boy’ left legacy of medical advances

February 22, 2009

‘Bubble boy’ left legacy of medical advances

07:29 PM CST on Sunday, February 22, 2009 Associated Press HOUSTON —

A quarter century after a cute child known as “the boy in the bubble” died, he has left a legacy of remarkable medical advances as well as some lingering ethical questions.

David Phillip Vetter lived nearly his whole life inside a series of sterile plastic bubbles, waiting for a cure for his fatal immune disease. As a captivated public watched, he grew up isolated from both germs and human touch before dying, at age 12, after a then-experimental bone marrow transplant failed.

Sunday was the 25th anniversary of his death. “It’s such a great human interest story, how so many people came to care about him,” James Jones, a former University of Houston historian, told the Houston Chronicle for a story in Sunday editions.

“Most medical stories have a flash-in-the pan quality, but David’s story didn’t go away. For 12 years, thanks to news coverage around his birthday, he captured hearts worldwide.” The ethical questions involve David’s role as a sort of living experiment.

But some bioethicists argue it was a classic example of doctors promising more than medicine could deliver and creating an unacceptable quality of life that took a toll on his emotional well-being.

There’s less debate about David’s medical legacy.

Doctors say he contributed enormously to a better understanding of clinical immunology that has resulted in better treatment for many diseases.

Among the lessons doctors learned in David’s case were that viruses can cause cancer. He also was the source of DNA that helped identify the gene that causes immune deficiencies, a discovery that led to a test for the disease in newborns, when it is most effectively treated.

“A lot of kids are alive today because David was here,” his father David J. Vetter said last week in a rare interview. “Perhaps it was meant to be—that he was the little guy through whom doctors and the world were meant to learn about the immune system.”

Vetter said it was “kind of unbelievable it happened to us, plain, ordinary people.” Marveling at his family’s ability to cope, he said it was like “the whole world came crashing down” when David was diagnosed.

David had severe combined immunodeficiency, or SCID, an inherited condition in which someone lacks the white blood cells that fight infection. It afflicts 40 to 50 babies born every year in the United States and is fatal within a year or two without treatment.

In 1971, the year David was born, the only hope was a bone marrow transplant from a donor whose blood matched perfectly.

Because the Vetters knew there was a chance David would have the immune condition—their first son died of SCID in infancy—David was delivered by Cesarean section in a sterile operating room at Houston’s Texas Children’s Hospital.

Immediately, infant David was whisked into a sealed bubble intended as a stopgap measure until a match could be found—hopefully, his sister.

“The Vetters were the only parents who asked if we could protect their boy,” said Dr. Mary Ann South, a pediatric immunologist and one of David’s doctors. “We’d treated seven or eight children with the disease and all of them died. Nothing worked, and they never lived long enough for us to learn about the disease.”

But after his sister’s blood did not match, the wait for a match or any kind of cure dragged on.

The boy with large, dark eyes and a shock of dark hair loved Star Wars films and the Houston Oilers.

He longed to drink a Coke and walk barefoot on the grass. He was a straight-A student taught by telephone.

NASA designed a space suit so he could walk outside, but David didn’t take to it. In late 1983, as David began losing hope he would ever leave the bubble, doctors told the Vetters of a promising new bone marrow transplant technique using less-than-perfect matches.

The transplant seemed to work well initially. But in early 1984, David began showing signs of illness and soon was removed from the bubble for treatment.

When he died Feb. 22, 1984 of a form of lymph cancer caused by an undetected Epstein Barr virus in the transplant, it made headlines worldwide.

A recent study found that bone marrow transplants, even imperfectly matched ones, work 90 percent of the time if performed within three months of birth.

David’s life and legacy are remembered through dramatic works, music and sculpture.

“He never touched the world,” reads David’s epitaph on his gravestone. “But the world was touched by him.”

Linkback url: http://www.khou.com/news/state/stories/khou090222_mp_bubble-boy-legacy.410d16a5.html


Italian professor makes scientific breakthrough

February 22, 2009

Italian professor makes scientific breakthrough

Dr. Alessandro Aiuti introduces new gene therapy to treat “bubble” syndrome

By Mariella Policheni

Forced to live within the confines of the home, unable to have contact with the outside world or to live a normal life like other children – those afflicted by Severe Combined Immunodeficiency Disease (ADA-SCID) can finally smile.
The treatment administered by the team guided by professors Alessandro Aiuti and Maria Grazia Roncarolo at the Istituto San Raffaele, has been proven to be effective: the final results of the experimentation that began in 2000 were published in the New England Journal of Medicine.
It is a therapy that has changed the lives of many “bubble babies” – so called because they are forced to live in a sterile environment – who are now finally free to go out, whether it’s to school, or to play with friends. They are now able to lead a much more normal life.
Professor Aiuti is a medical researcher who boasts a brilliant scientific career. After acquiring his degree in medicine and surgery at the Università di Roma La Sapienza, and completing his doctorate in Human Molecular and Cellular Biology research at the same university, he went on to specialize in Haematology at the Università degli Studi di Milano. From 1994 to 1996, he did research at the Genetics Department at Harvard Medical School in Boston, and is currently associate professor of Pediatrics at the Univesità degli studi di Roma Tor Vergata. He has also published 63 scientific works in international magazines.

The stem cell gene therapy being used by your team has proven to be successful. How many children have you treated?

“Since 2000, we’ve successfully treated 12 children who came from all over the world. Among them was Parker, a Canadian child.”

We’ve been following Parker DesLauriers’ story. What can you tell us about this case?

“A year and a half has passed since Parker underwent treatment. The results are good. Parker is recovering and his immune system is returning to normal function, so we are satisfied with his response to the therapy.”

Will Parker have to return to Milan for a checkup?

“Parker is a child who is growing nicely, and will return to Milan two years after the therapy.”

How did you apply the technique?

“We remedied the defect in the stem cells by taking bone marrow from children and then transplanting back their own marrow. By doing this, the cells made their way back to the bone marrow where they began producing blood cells including lymphoid cells – the cells that protect us from infections but that have been missing in these children since birth.”

Can gene therapy involving stem cells treat other illnesses? What are your goals for the future?

“Goals for the future are to expand the use of stem cells to the Wiskott-Aldrich Syndrome, another form of immunodeficiency, and to Metachromatic Leukodystrophy, a degenerative nervous system condition.”

This Italian research demonstrates the excellent preparedness of Italian scientists. You live and work in Italy, but many other researchers have leftthe country. Is it difficult to work in Italy? Why did you stay?

“I returned after two years in Boston, because I believed in the value of Italian research. We have many excellent scientists. It is possible, by carrying out high-quality research, to obtain results – for us, this was made possible thanks to the Fondazione Telethon. Unfortunately, government funding during recent years is still not enough to draw researchers back to Italy. It’s very important to have more investment in research. Good quality work can be achieved in Italy, and this example shows that we need to have more faith in research.”

Your work is very difficult with a high degree of commitment but also a lot of satisfaction. How do you feelabout being able to save the lives of the many children who come to Milan each year from all over the world?

“I am a doctor above all, so seeing tangible results from many years of laboratory research is great satisfaction – especially seeing children grow up to be healthy, and to see them playing. For me, it’s like having many offspring scattered throughout the world – it’s the source of great joy.”

Publication Date: 2009-02-22
Story Location: http://www.tandemnews.com/viewstory.php?storyid=8935


Gene therapy cures ‘bubble boy disease’

February 4, 2009

Gene therapy cures ‘bubble boy disease’

NEW YORK — Gene therapy seems to have cured eight of 10 children who had potentially fatal “bubble boy disease,” according to a study that followed their progress for about four years after treatment. The eight patients were no longer on medication for the rare disease, which cripples the body’s defenses against infection. The successful treatment is reported in Thursday’s issue of the New England Journal of Medicine and offers hope for treating other diseases with a gene therapy approach.

Bubble boy disease is formally called severe combined immunodeficiency, or SCID. This genetic disorder is diagnosed in about 40 to 100 babies each year in the United States. The nickname comes from the experience of a Houston boy, David Vetter, who became famous for living behind plastic barriers to protect him from germs. He died in 1984 at age 12.

He had the most common form of SCID. Recent studies found that gene therapy produced impressive results for that form of the disease, but also carried a risk of leukemia.

The new study involved a different, less common form of SCID – and one that holds a key position in medical history. In 1990 it became the first illness to be treated by gene therapy, according to the U.S. government. Two Ohio girls improved but continued to take medication.

This form of SCID arises in babies with a genetic defect that leaves them deficient of an enzyme called adenosine deaminase.

Patients can be treated with twice-weekly shots of the enzyme or a bone marrow transplant, but the medicine is expensive and marrow transplants don’t always work.

Gene therapy for the new study was performed in Italy and Israel. Researchers removed marrow cells from the patients, equipped the cells with working copies of the gene for the enzyme, and injected the cells back into the patients. In most cases, that was done before age 2.

The journal article reports the outcome two to eight years later, with an average of four years. All 10 patients were still alive, but two needed further treatment. None showed signs of leukemia or other health problems from the therapy, the researchers said.

Dr. Donald Kohn, a SCID expert at Childrens Hospital Los Angeles and the University of Southern California, said scientists are trying to understand why gene therapy produces a leukemia risk with the most common form of SCID but not the enzyme-related form.

The new findings are good news for the idea of using gene therapy to treat some other blood cell disorders, including sickle cell disease, said Kohn, who didn’t participate in the new study.

linkback url: http://abclocal.go.com/wabc/story?section=news%2Ftechnology&id=
6631182&rss=rss-wabc-article-6631182


New gene therapy could help Lehi’s ‘bubble girl’

February 3, 2009

Tuesday, 03 February 2009

New gene therapy could help Lehi’s ‘bubble girl’

Ace Stryker – Daily Herald

To see the video:  http://videos.heraldextra.com/p/video?id=3035039

A Lehi mother says she’s looking into experimental gene therapy to help her 7-year-old daughter, who was born with “bubble boy disease,” after European scientists cured eight of 10 children using the method.

Emily Heaps was born with severe combined immunodeficiency, a genetic defect that robs the body of its natural immune system. Contrary to popular belief, Emily doesn’t live in a bubble; her world is kept clean using equal portions Lysol and diligence. But since a bone marrow transplant last August, she’s been mostly isolated at home as her system recovers. It will be eight months before the family has a good idea of whether her body will accept the transplant, said her mother, Jill.

“She could start rejecting any time,” she said, noting that Emily should be able to return to school and church when the wait-and-see period is up.

But if the transplant doesn’t take, Jill said the family is encouraged by the results of gene therapy coming out of Europe. She said Emily’s doctors are looking into the test cases and could pursue something similar if necessary.

“That’s definitely an option if this transplant doesn’t work,” she said. “The first option is always the bone marrow transplant if you can have a match.”

There are concerns with the gene therapy route, Jill said: Some patients have developed leukemia as a result. But faced with the decision between that and no treatment — which would inevitably be fatal — it’s not a difficult choice, she said.

“When you get to the point where you don’t have a choice, you’re going to try anything you can,” she said. “If you have other choices, you always go for those first.”

The eight patients in Italy and Israel who were cured with the gene therapy are no longer on medication for the rare disease. The successful treatment was reported in last Thursday’s issue of the New England Journal of Medicine.

Severe combined immunodeficiency is diagnosed in about 40 to 100 babies each year in the United States. The nickname comes from the experience of a Houston boy, David Vetter, who became famous for living behind plastic barriers to protect him from germs. He died in 1984 at age 12.

Emily’s strain of SCID — a relatively rare one caused by a mutation in the gene that encodes a protein called adenosine deaminase — is one that holds a key position in medical history. In 1990 it became the first illness to be treated by gene therapy, according to the U.S. government. Two Ohio girls improved but continued to take medication.

In the test cases, researchers removed marrow cells from the patients, equipped the cells with working copies of the gene for the enzyme, and injected the cells back into the patients. In most cases, that was done before age 2.

Dr. Donald Kohn, a SCID expert at Childrens Hospital Los Angeles and the University of Southern California, said scientists are trying to understand why gene therapy produces a leukemia risk with the most common form of SCID but not the enzyme-related form.

The journal article reports the outcome two to eight years later, with an average of four years. All 10 patients were still alive, but two needed further treatment. None showed signs of leukemia or other health problems from the therapy, the researchers said.

• The Associated Press contributed to this report.
Ace Stryker can be reached at 344-2556
linkback url: http://www.heraldextra.com/content/view/298260/17/lThis e-mail address is being protected from spam bots, you need JavaScript enabled to view it
<!–
document.write( ‘</’ );
document.write( ‘span>’ );
//–>


%d bloggers like this: