Scanning the DNA of sick infants using a new speed-reading method can diagnose rare genetic disorders in two days instead of weeks, according to research that brings gene mapping a step closer to everyday hospital use.

Researchers at Childrens Mercy Hospitals and Clinics in Kansas City, Missouri, created software that takes raw data from DNA scanning machines and combs though hundreds of genetic disorders to spot disease-causing mutations. The system provided likely diagnoses for three of four sick babies in about two days, results published in Science Translational Medicine found.

The new method has the potential to make genome sequencing practical for neonatal intensive care units, enabling doctors to diagnose mysterious genetic diseases more quickly, said Stephen Kingsmore, director of the Center for Pediatric Genomic Medicine at Childrens Mercy and a study senior author. Fast diagnoses of sick babies could lead to life-extending treatments sooner in some or help avoid futile, costly therapies in others.

This is the biggest breakthrough in this technology for clinical applications we have seen in a few years, said David Dimmock, a geneticist at the Medical College of Wisconsin and Childrens Hospital of Wisconsin in Milwaukee, who wasnt involved in the study. The ability to sequence and interpret a genome in less than week is huge.

Dimmock said researchers at his institution were working on a similar fast genome interpretation system, but hadnt published the results yet. They beat us to the punch, he said.

There are about 3,500 known genetic diseases of which 500 have treatments, Kingsmore said. Many of these genetic illnesses hit young kids. Roughly 20 percent of infant deaths are caused by genetic conditions, according to the study released today.

The Childrens Mercy Hospital system was made possible in part by a new sequencing machine developed by San Diego-based Illumina Inc. (ILMN) that can decode an entire DNA sequence of a person in one day. This generates a colossal volume of raw data that must be analyzed by expert genetic researchers, a process that previously has taken weeks or months.

Heres where the system devised by Childrens Mercy researchers comes into play. Kingsmore and his team devised smart software that allows treating doctors to enter in a sick babys symptoms. The software then matches these reported symptoms to known genetic diseases that have similar symptoms, and scans through the babys genome results for likely harmful mutations in relevant genes.

We think this is going to transform the world of neonatology, Kingsmore said during a conference call with reporters. Until now, this was just not possible to get whole genome scan results quickly enough to help sick newborns in intensive care units, he said. Babies either died or else got better and were discharged home before the results of a gene test were returned.

For cases in which treatments are available, spotting the cause of a disease sooner may allow treatments to be started before it is too late, he said. Kingsmore estimated the total cost of the test to be about $13,500.

The rest is here:
Inherited Diseases Found Sooner in Newborns With DNA Scan

Is gene therapy finally becoming a reality? The European Commission is poised to authorize, for the first time in the Western world, the commercialization of a gene-therapy product. Called Glybera (alipogene tiparvovec), it is designed to treat a rare genetic defect involved in fat metabolism.

Success has been a long time coming. Gene therapy was first administered more than 20 years ago, to a child who had a rare disorder of the immune system called adenosine deaminase (ADA) deficiency. Since then, it has struggled to find its place in medicine amid a roller coaster of successes and setbacks, hype and scepticism that has little precedent in modern times. Although the approval of Glybera is a positive move, it is unlikely to herald a new age of gene therapies not without significant changes to the system. It is no coincidence that no gene therapy has yet been approved in the United States and that no other gene-therapy product is being considered by regulators in Europe.

Here is why. The design, development and manufacture of products such as Glybera a virus engineered to carry a correct copy of the defective gene is complex and done mostly in academic centres. Yet legislation introduced in the past decade in Europe and the United States demands that these products be produced under the same rules that cover conventional drugs, in establishments operated with industry-like standards and certified by government agencies.

This is a formidable challenge for academic centres, which tend to lack the necessary human and financial resources. So why is the development of gene therapy focused there, and not in industry, which seems better suited?

The first reason is the financial uncertainty generated by the complex, confused and poorly harmonized regulatory environment as the history of Glybera shows. At first, the application for its authorization received a negative opinion from two committees at the European Medicines Agency (EMA): the Committee for Advanced Therapies (CAT) and the Committee for Human Medicinal Products for Human Use (CHMP). Only when another body, the Standing Committee of the European Commission, asked the EMA to reconsider the application in a restricted indication did the CHMP eventually recommend approval under exceptional circumstances, requiring post-marketing studies and the set-up of a restricted-access programme. The Dutch firm Amsterdam Molecular Therapeutics, the inventor of Glybera, did not survive the process, and became known as uniQure after refinancing.

Lack of resources is a second reason. For many years, the drug industry stayed away from gene therapy, perceiving it as a dangerous technology of dubious efficacy that was too complex to develop and targeted too small a market.

There are some positive signs, because this last perception, at least, is changing: the industry now recognizes that rare diseases and orphan-drug legislation provide attractive opportunities. Some recombinant proteins and monoclonal antibodies originally developed as orphan drugs have been repurposed for larger indications.

The industry now recognizes that rare diseases and orphan-drug legislation provide attractive opportunities.

An example of how academia and industry could cooperate comes from the recent alliance between the drug giant GlaxoSmithKline (GSK) in London, and the charity-funded San Rafaelle Telethon Institute for Gene Therapy (TIGET) in Milan, Italy. GSK gained an exclusive licence to develop and commercialize the ADA treatment, and will co-develop with TIGET gene therapies for six more genetic diseases. The contribution of public or charity-funded organizations in early development phases lowers the cost and risk of investing in diseases with a tiny market, and gives the industry access to technologies that can be expanded to more profitable applications, thereby repaying the investment and allowing resources to be fed back into rare diseases. Unfortunately, promising therapies for hundreds of orphan diseases are unlikely to attract similar industrial interest.

So, how do we ensure that scientists will continue to develop such treatments? Should they all turn to the hospital exemption, which permits experimental therapies to be manufactured and used under the responsibility of a physician without regulatory supervision?

Continued here:
Gene therapies need new development models

A new method of genetic testing appears to be able to help doctors diagnose critically ill babies more quickly than ever before, according to a new study.

The method allows doctors for decode a baby's entire genome in two days -- breathtakingly fast compared to current methods that can take six weeks or more.

In the new study, the researchers report using the approach to decode the entire genomes of six acutely ill newborns admitted to neonatal intensive care units, two of whom had already been determined to have genetic diseases. What they found in this proof of concept, they said, could be used in the future to more quickly diagnose sick newborns and treat them early.

The study was published Wednesday in the journal Science Translational Medicine.

"We think that we have come up with a solution for the tragic families who have a baby who's born and the doctors are not sure of what the cause of the baby's illness is," said the study's senior author, Dr. Stephen F. Kingsmore, director of the Center for Pediatric Genomic Medicine at Children's Mercy Hospitals and Clinics in Kansas City, Mo.

Many of the 3,500 known genetic diseases cause medical problems during the first month of life, the researchers wrote in their study. In the United States, over 20 percent of infant deaths are caused by genetic disorders and birth defects.

"Up to one third of babies admitted to a neonatal intensive care unit in the United States have genetic diseases," Kingsmore said, adding that babies with genetic problems often die or are sent home before a diagnosis is made.

For families coping with the tragedy of a sick newborn, the test may make a big difference.

"The family doesn't know what's going on," Kingsmore said. "The doctors are working heroically to figure out what's wrong. That can go on for weeks."

Armed with an early genetic diagnosis, Kingsmore said that doctors can communicate more clearly with the family.

Original post:
Fast Gene Screen May Help Sick Babies

CHICAGO (Reuters) - U.S. scientists have sequenced the entire genetic code of four gravely ill newborns and identified genetic diseases in three of them in two days, quick enough to help doctors make treatment decisions.

Doctors behind the preliminary study released on Wednesday say it demonstrates a practical use for whole genome sequencing, in which researchers analyze all 3.2 billion chemical "bases" or "letters" that make up the human genetic code.

"It is now feasible to decode an entire genome and provide interim results back to the physician in two days," said Dr. Stephen Kingsmore, director of the Center for Pediatric Genomic Medicine at Children's Mercy medical center in Kansas City, Missouri, whose study was published in the journal Science Translational Medicine.

The study tested two software programs developed at Children's Mercy that were used in conjunction with a high-speed gene sequencer from Illumina called HiSeq 2500, which can sequence an entire genome in about 25 hours.

The company helped pay for the study and company researchers took part in it.

Next-generation gene sequencing machines have driven down the cost of whole genome sequencing, but making practical use of the data has been more challenging, largely because of the time it takes to analyze all of the data.

As many as a third of babies admitted to a neonatal intensive care unit in the United States have some form of genetic disease. Treatments are currently available for more than 500 diseases, but identifying them quickly has been a problem.

Typically, genetic testing on newborns using conventional methods takes four to six weeks, long enough that the infant has either died or been sent home.

"Up until now, they have really had to practice medicine blindfolded," Kingsmore said in a telephone briefing with reporters.

Dr. Neil Miller, director of informatics at Children's Mercy, said the software programs help doctors identify which genes to test, and analyze the data quickly.

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Rapid gene machines used to find cause of newborn illnesses