Newsroom Archives: News

by Nell Greenfieldboyce on NPR.org

Listen to the story on All Things Considered on NPR

published January 13, 2011

A newly developed test could screen would-be parents for hundreds of different disease genes, to make sure they are not passed on to any future children.

The test’s makers say it should cost less than $400 and that routinely offering it to prospective parents could someday eliminate many deadly childhood diseases.

“We definitely want it to be pre-pregnancy. We do want it to be couples,” says Stephen Kingsmore, a physician-researcher at Children’s Mercy Hospital in Kansas City, Mo., who led the team that developed this new test. “I think it’s going to be a personal decision, whether a couple wants to be tested.”

The inspiration for this new test came from Craig and Charlotte Benson, of Austin, Texas. In 2008, their daughter Christiane was diagnosed with Batten disease, a rare neurodegenerative disorder that currently has no cure. It progresses from vision loss to memory problems and seizures, and eventually death.

“Both her mom and I carry a gene mutation, a single gene mutation,” explains Craig Benson. He and his wife didn’t know they were carriers before they had children — indeed, they’d never heard of Batten disease.

A Test For Rare Genetic Diseases

Craig Benson works for a biotech company, so soon after his daughter was diagnosed, he and his colleagues were discussing how difficult it is for rare childhood diseases to get much attention or research that could lead to cures. They wondered about new ways of trying to prevent these diseases.

They knew that one devastating childhood disease, Tay-Sachs, has been virtually eliminated in people with Eastern European Jewish ancestry. This has been done by offering screening tests to would-be parents with that background. If both parents carry the Tay-Sachs mutation, they can take steps so that they won’t have a baby with this disease.

“We thought, you know, that’s a great idea and a great strategy. Why is that not more broadly applied?” says Benson, who noted that DNA testing technology has been advancing rapidly.

He and his colleagues approached Kingsmore, who was then at a nonprofit called the National Center for Genome Resources in Santa Fe, N.M. They asked him if it would be possible to make an affordable test that could screen all prospective parents for numerous rare genetic diseases.

This week, in the journal Science Translational Medicine,Kingsmore’s team describes that test. For less than $400, it can check a person’s DNA for all mutations in genes related to nearly 448 severe childhood diseases.

Technology Advancing Rapidly

And Kingsmore says that’s just the beginning.

“Over the next six months we’ll be taking the number up to 580 conditions,” he says, “at which point we’ll have represented just about every childhood disease that’s severe enough to merit inclusion.”

He says this test is relevant to everyone thinking of having a child, because their research shows it’s common for people to carry mutations.

“On average we found that each of us carries two or three mutations that could cause one of these severe childhood diseases,” Kingsmore says. Of course, a person would have to be unlucky enough to be having a baby with someone who just happened to be carrying a mutation for the same rare disease.

Right now, preconception genetic screening is recommended for just a few diseases — like Tay-Sachs and cystic fibrosis — in certain populations that have a higher risk.

But Laird Jackson, an expert in prenatal genetic testing at Drexel University, says the technology for widespread preconception screening is clearly already here and should advance rapidly.

“So it really does change things from thinking about its involving just a subset of the population to involving the whole population,” Jackson says. “Everybody has something to think about here, and if testing becomes available, will have something to decide about.”

A Bold Plan For Eliminating Diseases

Already, a couple of companies offer a routine preconception screening test for couples. For example, one test, sold by a company called Counsyl in Redwood City, Calif., is offered through doctors and IVF clinics. But Kingsmore says these currently available tests screen for far fewer diseases and can detect only known mutations — and he says for many rare disorders, all the mutations are not known.

This new test could become widely available soon, and Benson wants to offer it through a nonprofit he started, the Beyond Batten Disease Foundation, so that doctors could provide screening to everyone who wants it.

Benson admits that trying to eliminate rare diseases this way is a bold plan.

“I don’t know that we’ve really sat down and contemplated all of the impact that this test and this idea might have,” he says.

He just hopes it means other families won’t have his family’s experience — getting blindsided by a devastating disease that they’d never even heard of.

http://www.npr.org/2011/01/13/132908098/new-gene-test-screens-nearly-500-childhood-disease

by Mary Ann Roser in the Austin American Statesman

published January 12, 2011

An Austin couple, on a quest to find a cure for their terminally ill daughter, spearheaded a discovery of a genetic test that could one day help would-be parents discover if they are at higher risk for having a baby with a genetic disorder.

The test can’t save Christiane Benson, the 8-year-old daughter of Craig and Charlotte Benson of Austin, who has Batten Disease, a neurodegenerative disorder that leads to blindness, mental deterioration, a loss of motor skills and death typically in the teens or early 20s. But some of the money ultimately raised by the testing will be used to fund research aimed at finding a treatment or cure for Batten Disease. The rest will go toward improving the test, said Craig Benson, 48.

A paper published today in Science Translational Medicine describes the “next-generation sequencing” technology that the researchers say could help prevent parents from unwittingly passing diseases to their children. Researchers said the paper, in which they describe how they examined the entire genetic code of 104 human blood samples, also contains some surprises that could enhance understanding about disease inheritance.

The test would be able to detect some 448 devastating rare disorders.

The Bensons, below, founded the nonprofit Beyond Batten Disease Foundation in August 2008 after Christiane was diagnosed. They have raised several million dollars and dedicated more than $1.5 million toward developing the genetic test.

“What this means for Christiane … is the faster we can generate funds, the faster we can help find something that can slow or stop this disease,” Craig Benson said. “Beyond that, I would say, for Christiane, this is her legacy.”

Researchers led by the nonprofit National Center for Genome Resources in Santa Fe looked for genetic mutations in the blood samples and found, to their surprise, that the average person carries about three recessive childhood disease mutations. If each parent carries the same defective gene, they have a one in four chance of having a child with the disorder. Christiane’s brother, Garland, 6, does not have Batten Disease.

The idea of the test is for couples to be screened before having a baby. If they found out they shared the same recessive gene, they could choose to adopt or have a baby another way. The journal article carries an editor’s note that says “it may be some time” before the new test is available. The Bensons and the researchers are more optimistic; they think the test will be on the market by the third quarter of this year.

The test was better than 95 percent accurate — about as good as one can be in a laboratory setting — but it needs to be validated by thousands of samples clinically before it can be offered to the public, said Dr. Stephen Kingsmore, the senior author of the paper.

A more detailed story will appear in tomorrow’s print edition of the Statesman.

http://www.statesman.com/blogs/content/shared-gen/blogs/austin/health/entries/2011/01/12/austin_parents_of_terminally_i.html

by Joseph Hall on healthzone.ca

When his daughter was five, Craig Benson noticed she was inching nearer the television set, bringing her books closer to her face.

Benson thought little Christiane might simply need glasses.

But whirlwind months of tests and medical specialists would find her worsening vision was due to something much more than myopia.

A most rare and catastrophic thing.

“A pediatric ophthalmologist in Houston . . . said ‘Well we’ve done a lot of tests. There’s one more thing we probably ought to test for just to rule it out; it’s probably the worst-case scenario,’ ” says Benson, the CEO of a Texas-based biotechnology company.

“And that’s the first time I’d heard the name Batten Disease.”

The disease, which attacks the eyesight before going after movement centres in the brain, also causes seizures and affects about 3 in every 100,000 children in Canada and the U.S.

Unknown to either, Benson and his wife Charlotte both carried a recessive gene for the ailment which, when passed on to their daughter, would doom her to death in her teens.

In the wake of Christiane’s 2008 diagnosis, Benson set up the Beyond Batten Disease Foundation to seek a treatment or cure for the ailment.

But he did something more. Through the foundation, he commissioned research to seek a diagnostic screen that would ensure future parents did not get blindsided by the lurking genes for hundreds of genetic disorders they could pass on to their children.

Wednesday, that test was unveiled.

And in one fell swoop, it holds out the possibility that many of the most devastating childhood genetic diseases could be largely eradicated in a generation.

The new and inexpensive screening test, presented in the journal Science Translational Medicine, can detect a couple’s risk of passing on some 580 congenital ailments to their offspring. The single test, which will be in trial use this fall, scans a prospective parent’s genome for rare “recessive” disease genes that can lurk benignly in their DNA and can show if they share the imperiling genes with their partner.

“We wanted to have a test at the end of the day which would cost about $500 dollars and yet would survey the risk for all catastrophic childhood diseases,” says Dr. Stephen Kingsmore, the senior study author.

In creating and testing the screening device, researchers also discovered – to their shock — that we all carry an average 2.8 of these dormant disease genes.

“On average you or I or anybody in a North American population has two to three catastrophic disease mutations in their genome,” Kingsmore says. “If you are starting to have a family, this is the type of information you might want to know.”

Known as carriers, parents with recessive genes for diseases like cystic fibrosis, dwarfism or sickle cell anemia do not suffer from the associated ailment. But they risk passing it off to their children if their partner also has the mutant gene.

Each of us carries two copies of almost all of our genes, one each from our mother and father. In the case of genetic illnesses, both recessive genes need to be present before the disease or condition will develop.

Parents with the same recessive disease genes run a one in four risk of passing the ailment off to their children.

“You might want to know whether or not your partner or your spouse shares risk for any of the same diseases that you do,” says Kingsmore. “And if that was indeed the case you’d be well advised to get genetic counselling before you got pregnant.”

Testing of the technology will begin at Kansas City’s Children’s Mercy Hospital over the coming months and a working prototype should be set for clinical trials by the fall, says Kingsmore, director of the facility’s pediatric genome centre.

It should be available for similar trials in this country soon after.

In the past 25 years, more than 1,100 disease-causing genes have been identified. While the new screen now captures the most common ones, more are being added all the time, Kingsmore says.

The device works by focusing on segments of DNA where the recessive genes are known to exist, and reproducing those specific snippets thousands of times over. It then sends those amplified DNA segments through a high-powered sequencer to determine whether the genes are present in their healthy or mutated forms.

“These technologies are immensely powerful and they are reducing the cost of genome analysis thousands of fold,” says Kingsmore. “What we’ve done in this paper is to apply that technology for the first time to something which would be a routine doctor’s test.”

He estimates the cost of a single screen, which would use computer analysis to create an easily interpretable report, would be around $500.

Currently, in Canada only a few genetic illnesses are commonly screened for in couples prior to conception, and even then, only for specific high-risk populations. These include cystic fibrosis in northern European populations and Tay-Sachs disease in Ashkenazi Jewish populations.

In the case of Tay-Sachs, parental screening over the last 40 years has reduced the occurrence of the lethal neurological ailment by 90 per cent.

“That’s been fabulously successful; we’ve seen Tay-Sachs disease almost be eradicated . . . because they did (the screening) before marriage to see if indeed you were both carriers,” Kingsmore says.

The Tay-Sachs success, Kingsmore argues, shows that routine screening for all the inherited diseases that his technology will allow would lead to similar reductions in the other ailments. As well, he says the low cost for a test that captures a whole spectrum of ailments would make the screens affordable to health-care systems for population screening.

“Each of the disorders in and of itself is rare, but when you multiply that by 600 diseases or so, it becomes cost-effective,” he says. “That’s why it hasn’t been done before; the cost of testing for just one disease up until now has been hundreds or thousands of dollars.”

Though rare, with some affecting less than one in a million children, the genetic diseases together account for 20 per cent of all infant deaths and about 10 per cent of pediatric hospital admissions.

Kingsmore says parents who find they have common disease genes could receive genetic counselling about the nature of the ailment and the chances their children will inherit it.

Benson says adoption or in vitro fertilization options could help parents circumvent the risk.

If they decide to have children, regardless, prenatal genetic screening could determine if the fetus will develop the condition. This pre-birth diagnosis can lead to early medical treatments for the many diseases that have existing therapies, Kingsmore says.

But it also raises the spectre of selective abortion for many conditions — like forms of dwarfism and deafness — that are not lethal or largely treatable.

Unlike Tay-Sachs, which is invariably debilitating and lethal, many genetic disorders have a wide severity spectrum, says Dr. Jeff Nisker, a medical ethicist and professor of obstetrics and gynecology at the University of Western Ontario.

So any use of such an all-encompassing test must be accompanied by a genetic counselling mechanism to explain to parents what those variable outcomes might be for any given ailment, he says.

Nisker also says the test would require a broad discussion amongst Canadians about the types of conditions that can be legally screened for.

Kingsmore says the screen can also be used to diagnose genetic diseases in children like Christiane Benson.

“We can shorten that horrible window when parents are going from . . . specialist to specialist not knowing what’s wrong with their child and feeling totally helpless,” he says.

Benson, whose foundation spent about $1.5 million to fund the screen’s development, says that any profits from its use will be poured back into the fight against Batten Disease and other genetic ailments.

http://www.healthzone.ca/health/newsfeatures/research/article/920592–new-test-can-detect-more-than-500-genetic-diseases

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by Sandra Bretting

published in 2010

A recent $2.5 million gift to the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital has paved the way for noted Italian researcher Andrea Ballabio, M.D., to serve as visiting scientist at the institute for a year. Ballabio and his team conduct research into neurodegenerative disorders and lysosomal storage disorders, such as Batten disease.

The gift comes from Cherie and James C. Flores, who donated $2 million to the effort, and from the Beyond Batten Disease Foundation, which contributed $500,000. The foundation was established by Charlotte and Craig Benson, whose daughter, Christiane, was diagnosed with juvenile Batten disease in 2008.

Batten disease is a rare genetic disorder that attacks the nervous system. It was first documented nearly one hundred years ago, but research has been limited until now. There is no treatment and no cure. The earliest signs are subtle and often do not occur until a child is about 5 years old.

“It is heartbreaking to think that this disease will one day rob Christiane of her ability to see and walk and use her mind. And, eventually, it will take her from us, unless we act now,” Benson said.

“We have to believe that there’s an answer, and we are confident that there is hope for the future in terms of developing treatments for Batten disease,” he continued. “Texas Children’s Hospital is uniquely positioned to make progress against genetic disorders like Batten disease through facilitating collaborative research and recruiting world-renowned scientists like Dr. Ballabio and his associates.”

Ballabio has served on the molecular and human genetics faculty of Baylor College of Medicine. Currently, he is the scientific director of the Telethon Institute of Genetics and Medicine in Naples, Italy. He and his team recently discovered the gene that controls the body’s ability to degrade and recycle toxic molecules. The build-up of these molecules is the cause of numerous genetic disorders, including Batten disease, along with other neurodegenerative disorders such as Alzheimer’s, Parkinson’s and Huntington’s diseases.

“We have identified a ‘master’ gene that acts as a genetic switch,” Ballabio said. “By enhancing the function of this master gene, we can increase the clearance capacity of the cell and its ability to degrade toxic proteins. We believe this knowledge will help us develop better treatments and, ultimately, find a way to prevent these diseases.”

Phase one of Ballabio’s research at Texas Children’s began in July and is focused on the development of animal models for Batten disease and other disorders. Phase II, beginning next summer under the leadership of Ballabio’s research associate, Marco Sardiello, Ph.D., will investigate which drugs are able to promote activation of the master gene.

https://waystogive.texaschildrens.org/page.aspx?pid=1765

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