Scientists get on base against ALS
BY DAVID STEINKRAUS
Journal Times
Tuesday, July 31, 2007 7:12 PM CDT
Within the last two days, two pieces of medical research have provided new insights into Lou Gehrig’s Disease and where treatments may aim.

One, published online today by the New England Journal of Medicine, is the first to tie the most common form of the disease to several genes and one in particular. The other, published Tuesday in the Public Library of Science and led by a University of Wisconsin research team, reports a potential stem cell therapy for another type of the disease and has an unlooked for link to the New England Journal paper.

Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis or ALS, is a degenerative ailment in which people gradually lose control of their muscles, typically preventing them from going up steps and swallowing. It affects about 1 person in every 100,000, and there has been some research suggesting a higher incidence among Gulf War veterans.

ALS comes in two types. One, called familial because it’s inherited, comprises less than 10 percent of all cases. The other pops up with no warning, is called sporadic ALS, and is a disease of many parts.

“Many genes have to come together in the right constellation with an environmental factor to kick off the disease,” said Dietrich Stephan, director of the neurogenomics division at the Translational Genomics Research Institute in Phoenix. The institute is a nonprofit organization supported by both direct contributions and government grants, and it was formed to nurture the growth of genetic knowledge into therapies.

While research has linked a gene to familial ALS, the same hasn’t been true of sporadic ALS until now.

In the New England Journal of Medicine, Stephan’s group wrote that they tested several hundred people with ALS and looked for small variations in their genetic codes (called single nucleotide polymorphisms or SNPs). They found about 60, and in particular linked one to a gene strongly associated with the disease. The gene is called FLJ10986, and researchers also found the protein which the gene produces.

It’s not well known what this gene does, as evidenced by the fact that it has no name, said Clive Svendsen, professor of anatomy and neurology at the Waisman Center at the University of Wisconsin-Madison. Nor is the genetic discovery definitive, but it’s exciting that Stephan’s group found both a gene and its protein, he said.

A team led by Svendsen published the other piece of research, which was about a therapy for familial ALS. Svendsen’s group genetically altered human stem cells to produced a nerve growth chemical called GDNF, then implanted those stem cells in the spinal cords of rats modified to develop ALS. What the stem cells did is protect nerve cells from damage. What they didn’t do was stop decay of the connections between nerve cells and muscles, the team wrote.

This is where the two research papers cross even though they deal with two variants of the disease. Stephan’s team proposes that ALS may be a problem not of the cell itself but of the connection between nerve cell and muscle, and the SNPs they associated with ALS affect muscle function, which is where his group’s therapy faltered, Svendsen said.

His group’s research, Svendsen said, showed that nerve cells can be protected, and it also showed what may be the first use of stem cell therapy — to deliver drugs very specifically.

It’s too early, Stephan said, for people to run out and have themselves tested for this genetic variation. No drugs treat ALS, and even knowing the genetic risk would be useless because no one knows what environmental factor sets ALS in motion.

Yet Stephan is excited by what he foresees. “I think the fruits of all these genetic studies, this ALS paper in particular, are going to be borne in the next 10 years. And so I think in this next 10 years it’s really going to be an unbelievable time to be alive because we’re going to see so many new and interesting therapeutics coming on line.”

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