John,
I'm hoping those genes from the NIH study..are a match for some of the ones in this research....if they are from the sounds of it we may be seeing a light in the tunnel...towards the development of effective therapies...
It will be interesting to talk to Dr. MCCarty when he comes back.. I have alot of questions lined up and I'm sure you and others will as well....Lisa

Another Packard Center press release ...along the same lines as this research....hopefully they will find similar genes in the two studies....Lisa


November 29, 2006

FIRST INTERNATIONAL GENE SCREEN FOR TYPICAL ALS IS ON TRACK
Packard Center researcher, support, helps key study.

The largest-scale search for genes that underlie sporadic amyotrophic lateral sclerosis (ALS), the most common form of the disease, has crossed its first hurdle with the successful compiling of genetic information on more than 1,000 patients and controls.

Researchers in the study, supported by The Packard Center for ALS Research at Johns Hopkins, the National Institute of Neurological Disorders and Stroke (NINDS) and the ALS Association, present their initial findings this week at the 17th International Symposium on ALS/MDA at Yokohama, Japan. The symposium is the major venue, worldwide, for reporting studies on the disease.

It’s a good beginning to the first broad screening for genes for the “spontaneous” illness which, like all ALS, destroys the motor neurons that enable movement, including breathing.

Packard Center grantees Bryan Traynor and John Hardy,
Bryan Traynor discusses the gene project at the 2006 Packard Center symposium
both with the NIH, are leading an American and Italian team of researchers in the million-dollar project. “If all goes well,” Traynor says, “the work will clarify the role of genes—or lack of it—in sporadic ALS. That role has long been uncertain,” he explains. “We don’t know, for example, if sALS is triggered by a handful of interacting genes or genes plus environment or environment alone. Our work aims to clarify that.”

In the study, DNA was collected from patients and healthy controls and successfully scanned for specific patterns that appear more frequently in those with the disease than those without it.


Researcher John Hardy
Critical to the work—known to scientists as a high resolution, genome-wide association study—is its technology. It’s a high-throughput approach (that is, it treats many samples simultaneously) that uses robotics and just-available gene finder chips to mine each patient’s DNA for information with a speed and accuracy not possible six months ago.

The project, which began last spring, was completed in record time, reflecting the highly collaborative nature of the involved scientists and clinicians. The NINDS, for example, contributed the American samples in the study from among those that ALS clinicians at multiple medical centers nationwide sent to its new national repository.

The researchers anticipate important analysis and conclusion-drawing will occur in the next few months.

Finding genes that lead directly to ALS or that predispose people to the disease should provide new targets for therapies. In the decade since discovering the cause of some inherited forms of ALS—namely, a mutation producing a flawed version of the enzyme superoxide dismutase (SOD1)—a handful of other ALS-related mutations have been brought to light.

The genetic underpinnings of sporadic ALS, however, are far less certain. Sporadic ALS, affecting 90 percent of ALS patients, apparently arises spontaneously without family history. Even though the disease is clinically indistinguishable from the ALS that runs in families, different genes may be responsible for each. Something is held in common, however, in the way that they both kill motor neurons. That’s why a gene change identified in one type can help understand the other.

Finding a scientifically significant tie between a gene or genes and ALS in this work will set the stage for even larger international investigations. “But even if we get no associations,” says Traynor, “that would suggest that sALS isn’t gene-based, that we should focus instead on the environment.”


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Collection of samples of ALS patient DNA, earmarked for the repository established through the National Institutes of Neurological Disorders and Stroke (NINDS), is ongoing. ALS patients and caregivers can anonymously donate a small amount of blood and give clinical history to aid in the gene hunt. Donations continue to be accepted at Johns Hopkins and ALS centers at other major medical institutions, to aid in this and other projects that will uncover the reasons for the disease.The researchers were funded by the National Institutes of Health, the Muscular Dystrophy Association and the Robert Packard Center for ALS Research at Johns Hopkins.

Mayo is next step in ALS research
Fri, Dec 1, 2006
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Related Stories• Study gives hope to Lou Gehrig's patients - Fri, Dec 1, 2006
. By Jeff Hansel

The Post-Bulletin

Scientists at the Translational Genomics Institute analyzed the genomes of 3,200 individuals to find the genetic triggers of sporadic amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease.

Next, researchers are preparing a search for drugs to treat the devastating illness. They found 50 genetic anomalies involved in development of the incurable condition.

"These genes produce a sort of molecular glue that attaches motor neurons to muscle," says a TGen statement. "It appears that in ALS the nerve is able to peel off the muscle and, when that happens repeatedly, the nerves die."

Some of the genetic abnormalities have never been linked to ALS before.

To find them, researchers analyzed blood samples from 1,200 people with the condition, and 2,000 without.

"This does not mean we've cured ALS," said Dietrich Stephan, deputy director for discovery research at the Translational Genomics Institute (TGen), the non-profit company responsible for the research. This is a necessary and important step toward a cure."

The study was conducted in TGen's Phoenix facility.

Mayo gets involved

The next phase of research, though, will take place in the Collaborative Research Building on the Mayo Clinic campus in Scottsdale.

"That's exactly where we're going to be doing the bulk of these studies," Stephan said.

Translational Drug Development, or TD2, a partnership between Mayo and TGen, will use animal models to test drugs researchers believe have potential to block the effects of ALS.

Scientists will review the genetic abnormalities to see if molecules (in other words, drugs) can be found that would block negative effects on the human body, said Ron Schenkenberger, senior vice president for research and health-care services at the Muscular Dystrophy Association.

One key, he said, is whether the potential compounds are in drugs that are already on the market -- ones approved for other uses by the Food and Drug Administration.

It is not yet known whether treatments can be quickly developed as a result of the discovery, or will instead take many years -- longer than most currently diagnosed with the illness will survive.

But the MDA, which funded the research with a relatively small amount of money -- totaling $1.3 million, according to an MDA spokesman -- says there's a possibility that potential treatments could be found quickly.

That means a search through thousands of drugs already on the market. Because they've been through the FDA approval process, their side effects and risks are already known. That means if an existing drug is found that blocks the effects of ALS, it could be used almost immediately.

Failing that, developing a new drug could take years.

Hanging in the balance are the lives of 30,000 or more Americans now living with the knowledge that life expectancy after diagnosis with ALS, according to the MDA, ranges from two to four years. But famed scientist Stephen Hawking has survived with ALS for many years, Schenkenberger said.

ALS deteriorates nerve cells in the brain and spinal cord that control voluntary muscles, according to MayoClinic.org. Eventually, people who have ALS lose the ability to move their limbs and the muscles needed to breathe.

Using new "microarray" technology by Affymetrix of Santa Clara, Calif., TGen completed the analysis -- from start to finish -- in just nine months. That, says the MDA, shows the speed of research is ramping up.

"Just a couple of years ago, this experiment would not have been possible because there simply wasn't a technology that enabled scientists to sift through the three billion molecules in the genome to find the genetic abnormalities that cause disease," noted Sean George, vice president of the Academic Business Unit at Affymetrix, in a company statement. The study used the same kind of technology that powers supercomputers, George said.

"The quicker we can identify the anomalies, the quicker we can target those for possible intervention," Schenkenberger said.

How soon?

"The time horizon is, at its best, within the lives of people who are still with us -- at its worst within the next two waves of people who are diagnosed," Stephan said.
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