Welcome to the ALS News Network

Date : Tue, 05 Feb 2002

From: motterb@jhmi.edu

Welcome, to the Center for ALS Research at Johns Hopkins listserv. This e-mail newsgroup allows us to keep you informed about the latest information on ALS research and treatment.

The Center for ALS Research at Johns Hopkins is a collaboration of the world's best ALS scientists working rapidly to develop new treatments and find a cure for ALS, also known as Lou Gehrig's disease. It's the only institution of its kind dedicated solely to the disease. Research conducted by the Center is meant to translate from bench to bedside in an expedited time frame. Center scientists have made some of the most important discoveries in ALS, leading to advances in understanding and treatment of the disease.

The nature of ALS shapes the Center's aggressive, results-oriented scientific approach. ALS is a devastating, progressive neuromuscular disease that causes complete paralysis and loss of function -- including the ability to eat, speak and breathe -- and eventually, death. ALS progresses quickly and is not curable. Most patients die within five years of diagnosis.

To learn more about The Center for ALS Research at Johns Hopkins, including the latest information on ALS research and treatment, log on to http://www.alscenter.org.

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Rat Model Reveals Astrocyte Role in ALS

From: whubben@als-tdf.org

Date : Wed, 30 Jan 2002

New, Better Rat Model Reveals Astrocyte Role In ALS

Author(s): David Howland
Institute: Johns Hopkins School of Medicine and the Center for ALS: Research at Johns Hopkins Published: 30-Jan-2002

Article:
http://unisci.com/stories/20021/0130021.htm

A team of scientists led by drug maker Wyeth-Ayerst and Johns Hopkins has engineered and tested a new rat model of Lou Gehrig's disease they say is far easier to work with than earlier mouse models.  Because of their larger size, the rats should expedite evaluation of novel treatments, such as those using stem cells, as well as deepen understanding of the fatal disease also known as amyotrophic lateral sclerosis (ALS), the scientists say.

The "transgenic" rat, which carries a human gene, already has revealed the important role played by brain cells called astrocytes, a role obscured in mice.

The ALS rat, believed to be the first transgenic rat model of a neurodegenerative disease, moves from onset of symptoms through to ALS-like disability more quickly than ALS mice, making changes in cells in the rats more striking from day to day, the scientists report in today's online edition of the Proceedings of the National Academy of Sciences.

"The transgenic rats are a powerful tool," says neurologist Jeffrey Rothstein, M.D., director of the Center for ALS Research at Johns Hopkins and an author of the report. "Mice are just too small, for example, for reliable infusions into their spinal cords, the direction research on stem cell treatment is heading."

Scientists at Wyeth-Ayerst engineered the rats to carry an abnormal human gene for superoxide dismutase (SOD1), an enzyme that normally breaks down free radicals, highly reactive molecules that quickly damage DNA and kill cells. Faulty SOD1 behavior, caused by a number of different genetic mutations, is at the root of roughly one-fifth of inherited ALS cases.

The SOD1 rats, like the SOD1 mice before them, develop a disease very similar to ALS in humans, which is characterized by the death of motor nerve cells throughout the central nervous system. The rats are "symptom-free" for a longer time, but then deteriorate much more rapidly than the mice.

While the faster disease progression in rats might hide subtle effects of some potential treatments, the scientists point to the benefit of a model that can easily test stem cells and advance understanding of the disease. Stem cells are primitive precursors to other cells; embryonic stem cells can become any cell in the body, while so-called "adult" stem cells, like neuronal stem cells, are naturally destined to become the cells of a particular tissue.

So far, the new rat has revealed that specialized brain cells called astrocytes play a key role in the early steps of the disease. Astrocytes, which make up more than 50 percent of the brain's tissue, normally bridge the blood vessels and neurons in the brain.
 In these rats, before physical symptoms develop and for reasons
unknown, the main transporter for the neuron-exciting messenger glutamate begins disappearing from the astrocytes. Rothstein suggests the loss of the glutamate transporter may be a crucial initial step leading to the death of motor neurons, deaths that directly correspond to symptoms like limb paralysis.

Glutamate excites neurons, whipping them into a frenzy. The glutamate transporter in astrocytes helps maintain an appropriate balance of glutamate outside the neurons so these key brain cells aren't over-stimulated. When the transporter in astrocytes begins
disappearing, glutamate builds up outside the cells, and hence outside neurons, leading to "glutamate toxicity," suggests Rothstein.  "Our idea is that over-stimulation of neurons by glutamate can lead to the neurons' deaths, and we continue to uncover evidence supporting this hypothesis," he says. "That the SOD1 rats already have revealed what is likely a key step in the disease process bodes well for the future of this model."

How mutant SOD1 directly injures a cell is still a mystery, but the rat model should help scientists determine how the faulty enzyme leads to disease, says Rothstein.

In the central nervous system of human patients and SOD1 transgenic mice and rats, globs of faulty SOD1 proteins are found. Scientists know that loss of SOD1 function isn't to blame for the symptoms of ALS; instead, the faulty enzyme picks up a new, still unknown, function.

Finding the link between faulty SOD1 and the disappearing glutamate transporter should help clarify why the many SOD1 mutations appear in patients with inherited ALS and even in some non-inherited cases of the disease, says Rothstein.

The investigations were stimulated by The ALS Association, and funded by the National Institutes of Health, the Center for ALS Research at Johns Hopkins, the Spinal Cord Disease Foundation and the Ludwig Institute for Cancer Research. The Center for ALS Research at Johns Hopkins, formed in March 2000, is a collaboration of scientists worldwide rapidly working to develop new treatments and to find a cure for ALS.

Other authors on the study are principal investigator David Howland, Yijin She, Beth Goad, Jamie Erickson, John Kulik, Lisa DeVito, George Psaltis and Louis DeGennaro of Wyeth-Ayerst; Jian Liu and Don Cleveland of the University of San Diego and the Center for ALS Research at Johns Hopkins; and Nicholas Maragakis and Benjamin Kim of Johns Hopkins School of Medicine and the Center for ALS Research at Johns Hopkins. - By Joanna Downer

30-Jan-2002

Article Archived at: http://www.als-tdf.org/alstdf/research/hubben/
viewarticle.asp?id_article=285

Will Hubben whubben@als-tdf.org

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New Officers in the Stem-Cell Division
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SOURCE : The Washington Post
DATE : January 10, 2002
HEADLINE: New Officers in the Stem-Cell Division
BYLINE : Judy Sarasohn

After a big debut last year in the fight to save stem cell research, the Coalition for the Advancement of Medical Research -- CAMR -- has new officers and a group of some 60 member-organizations that won't let go of the issue this year.

Michael Manganiello, senior vice president and director of government relations for the Christopher Reeve Paralysis Foundation, takes over as president of CAMR, succeeding Larry Soler of the Juvenile Diabetes Research Foundation. Elisabeth Bresee Brittin of the Parkinson's Action Network is treasurer, and Kevin Wilson of the American Society for Cell Biology is secretary.

The coalition also includes such groups as the ALS Association, the
Juvenile Diabetes Research Foundation International, the American Diabetes Association, the American Pediatric Society, Cedars-Sinai Health System, Duke University Medical Center, John Hopkins Medicine and the University of Michigan.

Manganiello said the member-organizations, particularly the patient groups, aggressively lobbied lawmakers and the administration to prevent an outright ban on stem cell research. He noted that President Bush's first prime-time presidential address was on his decision to allow federal funding for limited stem cell research.

"We take a lot of credit" for that, Manganiello said.  Stem cells can develop into other types of tissue, which scientists believe could create new treatments for diabetes, ALS, Alzheimer's disease and other devastating afflictions. They believe that stem cells from embryos are more promising than similar cells in some adult tissues. Bush's decision limits federal funds to studies on stem cells
in existing colonies, or "lines."

Manganiello said that the coalition is in the process of determining its agenda for the year but that it will surely include monitoring of the implementation of the policy and fighting to expand funding. Congress is expected to take up cloning legislation this year that may have an impact on stem cell research.

"Our scientists are concerned that there are not enough lines to do
basic research," he said.