Bill-ut
06-26-2008, 01:30 PM
Robert Packard Center ALS News Network View this article online at:http://www.alscenter.org/news/briefs/080612.cfm IN ALS, IT'S NOT THE NUMBER OF AILING ASTROCYTES THAT COUNTS The spinal cord after an auto accident or some other physical traumacould best be described as being in a biological uproar. A wide varietyof cells disappear. The chemical environment changes. And of interest toPackard researchers is the sharp upturn in the number of astrocytes. Thestar-shaped cells that are motor neurons' companions quickly become farmore common - often within 24 hours of injury. This jump is likely protective, studies show; if you block theastrocyte response in lab rats after a trauma, for example, injury ismuch greater. "But in ALS, important differences exist," says Packard scientistNicholas Maragakis. Certainly, as in trauma, astrocytes increase in bothanimal models of the disease and in the humans who have it. The numbersin both are comparable. But somehow, any neuroprotection that astrocytes offer after a cut or ablow isn't apparent in ALS. "We really understand very little about howthese cells behave before or after symptoms appear, Maragakis explains,"and what's behind it." So he and colleagues aim to change that. A decade of research, much of it in Packard labs, shows that more thannumbers of astrocytes increase in injury or disease. The cellsthemselves balloon out and their internal chemistry changes as differentgenes switch on or off. And a host of recent studies in animal models of ALS points to a rolefor ailing astrocytes in motor neuron death. Astrocytic molecules thatclear toxins from the motor neuron environment, for example, are inshort supply. And clumps of abnormal protein clutter astrocytes'cytoplasm. "By the time ALS symptoms appear," Maragakis explains,"astrocytes are clearly far from normal and become more so as thedisease continues." They may not start ALS, but the diseased cellscertainly have a hand in its progress. The approach Maragakis and other Packard scientists are taking isthorough: to try to block the major astocytic changes in good animalmodels and see if that either halts or slows ALS. In the first of these studies, just reported in the journalExperimental Neurology, he blocked mature astrocytes from dividing. Histeam used two animal models of ALS, one, the classic SOD1 mouse modelthat contains a flawed gene for familial ALS. The other: mice whosecentral nervous system has been attacked by Sindbis virus. Both typestypically have a significantly higher astrocyte count than healthyanimals. The result was useful, though not glamorous. The already high astrocytenumber didn't increase. "That suggests that most of them come from adifferent source - stem cells," says Maragakis. (New research from hislab has confirmed this alternate stem cell source. Now it appears to bethe key one.) And of more interest, survival of the lab animals' motor neurons orsurvival of the animals themselves didn't change. "What this tells us,"he explains, "is that whatever astrocytes do to advance ALS most likelyhas to do with which genes are active or in how they affect the spinalcord environment. It's not the actual number of dividing astrocytesthat's so important." ___________________________________ About The Robert Packard Center for ALS Research at Johns Hopkinswww.alscenter.org Located in Baltimore, the Robert Packard Center for ALS Research atJohns Hopkins is a worldwide collaboration of scientists aimed atdeveloping therapies and a cure for amyotrophic lateral sclerosis (ALS),also known as Lou Gehrig’s disease. The Center is the only institution of its kind dedicated solely to thedisease. Its research is meant to translate rapidly from the lab benchto the clinic, largely by eliminating time spent waiting for grants andlowering institutional barriers to sharing scientific results. Scientists and clinician members of the Packard Center have moved drugsreliably and rapidly from preclinical experiments to human trials.Direct or indirect links to international biotech or pharmaceuticalcompanies bring the infrastructure and experience needed to makepromising drugs into therapies. Packard scientists are the first to propose and test a combinationapproach to drug therapy, a tactic that has worked for AIDS, cancer andother diseases. ALS is a progressive, disabling neuromuscular disease that causescomplete paralysis and loss of function - including the ability toeat, speak and breathe. ALS progresses quickly and is not curable. Mostpatients die within five years of diagnosis. _________________________________________Rebecca BergerResearch Program CoordinatorRobert Packard Center for ALS Research at Johns Hopkins5801 Smith Avenue | McAuley Suite 110Baltimore, MD 21209410.735.7678 direct410.735.7680 faxrberger6@jhmi.edu www.alscenter.org ************************************************** ******************************Click on the link below to unsubscribemailto:sympa@lists.johnshopkins.edu?sub ject=unsubscribe%20alscenter&body=PLEASE%20SEND%20THIS%20EMAIL%20OUT%20FOR%20UN SUBSCRIBING Please follow the instructions below if the above link does not work: Compose an email to: sympa@lists.johnshopkins.edu With Subject: unsubscribe alscenterNote: 'unsubscribe alscenter' should be on the SUBJECT line, NOT IN THE MESSAGE BODY. To contact the list owner: mailto:alscenter-request@lists.johnshopkins.edu******************** ************************************************** **********