Growth Factor in Stem Cells May Spur Recovery from Multiple Sclerosis May 21, 2012 A substance in human

n mesenchymal (Mesenchymln kmenov buky Nachzej se v kostn deni a mohou vytvet kostn, chrupavitou, tukovou, vazivovou tk a retikulrn s podporujc krvetvorbu. V kultue za specilnch podmnek ale mohou vytvoit i neurln nebo svalov buky, i buky cvnho epitelu.) stem cells that promotes growth appears to spur restoration of nerves and their function in rodent models of multiple sclerosis (MS), researchers at Case Western Reserve University School of Medicine have found. In animals injected with hepatocyte growth factor, inflammation declined and neural cells grew. Perhaps most important, the myelin sheath, which protects nerves and their ability to gather and send information, regrew, covering lesions caused by the disease. "The importance of this work is we think we've identified the driver of the recovery," said Robert H. Miller, professor of neurosciences at the School of Medicine and vice president for research at Case Western Reserve University. Miller, neurosciences instructor Lianhua Bai and biology professor Arnold I. Caplan, designed the study. They worked with Project Manager Anne DeChant, and research assistants Jordan Hecker, Janet Kranso and Anita Zaremba, from the School of Medicine; and Donald P. Lennon, a research assistant from the university's Skeletal Research Center. In MS, the immune system attacks myelin, risking injury to exposed nerves' intricate wiring. When damaged, nerve signals can be interrupted, causing loss of balance and coordination, cognitive ability and other functions. Over time, intermittent losses may become permanent. Miller and Caplan reported in 2009 that when they injected human mesenchymal stem cells into rodent models of MS, the animals recovered from the damage wrought by the disease. Based on their work, a clinical trial is underway in which MS patients are injected with their own stem cells. In this study, the researchers first wanted to test whether the presence of stem cells or something cells produce promotes recovery. They injected mice with the medium in which mesenchymal stem cells, culled from bone marrow, grew. All 11 animals, which have a version of MS, showed a rapid reduction in functional deficits. Analysis showed that the disease remained on course unless the molecules injected were of a certain size; that is, the molecular weight ranged between 50 and 100 kiloDaltons. Research by others and results of their own work indicated hepatocyte growth factor, which is secreted by mesenchymal stem cells, was a likely instigator.

The scientists injected animals with 50 or 100 nanograms of the growth factor every other day for five days. The level of signaling molecules that promote inflammation decreased while the level of signaling molecules that counter inflammation increased. Neural cells grew and nerves laid bare by MS were rewrapped with myelin. The 100-nanogram injections appeared to provide slightly better recovery. To test the system further, researchers tied up cell-surface receptors, in this case cMet receptors that are known to work with the growth factor. When they jammed the receptors with a function-blocking cMet antibody, neither the mesenchymal stem cell medium nor the hepatocyte growth factor injections had any effect on the disease. In another test, injections of an anti-hepatocyte growth factor also blocked recovery. The researchers will continue their studies, to determine if they can screen mesenchymal stem cells for those that produce the higher amounts of hepatocyte growth factor needed for effective treatment. That could lead to a more precise cell therapy. "Could we now take away the mesenchymal stem cells and treat only with hepatocyte growth factor?" Miller asked. "We've shown we can do that in an animal but it's not clear if we can do that in a patient." They also plan to test whether other factors may be used to stimulate the cMet receptors and induce recovery. 20. kv 2012 22:20:10 Dotovan studie "Nadac na opravu myelinu" veden vdci z univerzity "Case Western Reserve" v USA nalezla vylepen s mesenchymlnm kmenovmi bukami na zvecm modelu RS. "Nadace na opravu myelinu" dnes oznmila vsledky nov oven vzkumn studie publikovan v "Nature Neuroscience", kter ukazuje funkn zlepen lebou modulace imunitn odezvy a opravy myelinu s faktory odvozenmi z mesechymlnch kmenovch bunk na zvecm modelu RS. "Jsme nadeni s publikac tto dleit vzkumn studie kter zkoum nov cesty leby RS a kter zvrt pokozen zpsoben nemoc", k Dr. Robert Miller. "Od doby kdy jsme byli pouze v zatcch chpn toho jak mesenchymln kmenov buky poskytuj opravy lz myelinem tak s spodporou tto nadace pokraujeme hlobji v naich znalostech objevovn dalch generac leb RS kter spe stimuj lebu ne potlauj symptomy nemoci". Re: Potenciln nov leba pro opravu myelinu od Franta pon 21. kv 2012 22:48:15 trochu vc na Science Daily http://www.sciencedaily.com/releases/20 ... 104629.htm Vzkumnci z Case Western Reserve University School of Medicine objevili,

e ltka v lidskch mesenchymlnch kmenovch bukch, kter podporuje rst ukazuje, e spout obnovu nerv a jejich funkc na krysm modelu RS. U zvat do kterch byla vpravena injekce s hepatocyte rstovm faktorem, znt ustoupil a neurln buky zaaly rst. Pravdpodobn nejdleitj je, e myelinov izolant kter chrn nervy a jejich schopnost schromaovat a poslat informace, znovu vyrostl a obalil lze zapiinn nemoc. "Nejdleitj z tto prce je, e jsme identifikovali pvodce tohoto zotaven." k Robert H. Miller, professor of neurosciences at the School of Medicine and vice president for research at Case Western Reserve University.

Miller a Caplan (autoi studie) v roce 2009 oznmili e injekn vpravili lidsk mesenchymln kmenov buky do krysho modelu RS, zvata se uzdravila z pokozen zpsobenho nemoc. Na zklad jejich prce prv b klinick zkouky ve kterch jsou RS pacientm injekn vpravovny jejich vlastn kmenov buky. Vzkumnci v tto studii nejprve chtli otestovat zda-li ptomnost kmenovch bunk nebo jinch bunk bude podporovat zotaven. Injekc vpravili mym medium s mesechymlnmi kmenovmi bukami, odebran z kostn den, kter rostli/rostlo. Vech 11 zvat, kter maj verzi RS, vykzalo rychlou redukci jejich funknch nedostatk. Analzy ukzaly e nemoc zstvala ve svm kurzu bez toho aby molekuly byly vpraveny v urit velikosti; to znamen e se molekulrn vha pohybovala od 50 do 100 kiloDaltons. Vzkum jinch a vsledky jejich vlstn prce naznauj e hepatocyt rstov faktor, kter je vyluovn mesenchymlnmi bukami to pravdpodobn podporoval. Vdci vpravovali injekc zvatm 50-100 nanogram rstovho faktoru kad den po dobu pti dn. Mnostv signlnch molekul, kter podporuj znty se zmnilo zatmco mnostv signlnch molekul, kter potaj znty, vzrostl. Neurln buky rostly a nervy lec hol, dky RS, byly opt obaleny myelinem. 100 nanogramov injekce se jevily, e poskytuj o trochu lep zotaven.

K otestovn systmu dle vzkumnci zablokovali bunn receptory, v tomto ppad cMet receptory o kterch je znmo, e pracuj s rstovm faktorem. Jakmile zablokovali receptory s funkc blokovn cMet protiltky, tak ani mesenchymln kmenov buky a ani injekce hepatocytovho rstovho faktoru nemly dn vliv na nemoc. V jinm testu, injekce antihepatocytovho rstovho faktoru tak blokovaly zotaven.

"Mohli by jsme nyn dt pry mesenchymln kmenov buky a lit jen s hepatocytovm rstovm faktorem?" pt se Miller. " Ukzali jsme, e to meme dlat na zvecm modelu, ale nen jasn jestli to meme udlat u pacient." Oni maj tak v plnu testovat zdali by jin faktory mohly bt pouity k stimulovn cMet receptor a navodit zotaven. Fze 1 klinick studie veden na Clevelandsk klinice bude zkoumat innost novho zpsobu myelinov opravy pomoc mesenchymlnch kmenovch bunk. Polovina z 24 plnovanch pacient je ji do studie pihlena. The Myelin Repair Foundation Partners with Gencia Corporation to Advance Myelin Repair Therapeutics for Multiple Sclerosis (MS) ARATOGA, Calif. & CHARLOTTESVILLE, Va.--(BUSINESS WIRE)-The Myelin Repair Foundation (MRF) and Gencia Corporation today announced a collaboration to advance myelin repair therapeutic development for Multiple Sclerosis (MS). Through its unique Accelerated Research Collaboration (ARC) model, the Myelin Repair Foundation will partner with Gencia Corporation to assess the myelin regenerating capabilities of the companys proprietary therapeutic compounds for MS. Through this unique partnership, Gencia Corporation will work closely with researchers at the Myelin Repair Foundations Translational Medicine Center, a laboratory facility dedicated to the evaluation of promising multiple sclerosis candidates for myelin repair. Led by MRF personnel with extensive biopharma experience moving therapeutic compounds into the clinic, the MRF Translational Medicine Center investigates and advances promising myelin repair drug targets toward commercialization. The Myelin Repair Foundations patient-centric, collaborative approach to develop the next generation of MS therapeutics makes them an ideal partner for us to bring new treatments to the clinic, said President and CEO Allen Cunningham from Gencia Corporation. We are excited to work side by side with MRF, utilizing their novel myelin repair research tools and assays at the MRF Translational Medicine Center. With this partnership, we are well positioned to expedite myelin repair therapeutics development forward, meeting the needs of MS patients.

Gencias forward-thinking approach to remyelination aligns nicely with our goal to bring the next generation of MS treatments to patients, said Chief Research Officer Dr. Jay Tung, Ph.D, from the Myelin Repair Foundation. We are thrilled to be working with Gencia to examine new ways to treat MS. As a non-profit organization, we seek to partner with innovative companies doing exciting MS research in myelin repair. The Myelin Repair Foundations rigorous, industry-leading Translational Medicine Platform consists of its Translational Medicine Center, contract research organizations and the MRFs research consortium. The goal of the MRF Translational Medicine Platform is to ensure comprehensive validation of potential therapeutics into clinical development. About the Myelin Repair Foundation The Myelin Repair Foundation (MRF) (www.myelinrepair.org) is a Silicon Valley-based, non-profit research organization focused on accelerating the discovery and development of myelin repair therapeutics for Multiple Sclerosis. Its Accelerated Research Collaboration (ARC) model is designed to optimize the process of medical research, drug development and the delivery of new patient treatments. About Gencia Corporation Gencia Corporation is a privately held biopharmaceutical company focused on discovering and developing novel therapeutics to treat disease. The company's programs leverage the fundamental role that mitochondria play in health, aging and disease. Gencias pipeline contains biologics and small molecules for the treatment of central nervous system (CNS) disease, inflammation and rare genetic disorders. Contact: Myelin Repair Foundation Jennifer Chang (408) 871-2410 jchang@myelinrepair.org

Human ES Cells Progress Slowly In Myelin's Direction Apr. 10, 2009 Scientists from the University of Wisconsin report in the journal Development the successful generation from human embryonic stem cells of a type of cell that can make myelin, a finding that opens up new possibilities for both basic and clinical research. The cells the researchers made are called oligodendrocytes, which are responsible for making myelin in the central nervous system. Myelin forms an insulating sheath that surrounds nerve fibres, both protecting them and speeding up the transmission of nerve impulses. Its loss or damage has serious consequences, as is seen in the condition of multiple sclerosis, because without it nerves lose the ability to transmit impulses to each other and to function properly.

Unlike human embryonic stem (ES) cells, it's relatively easy to persuade mouse ES cells to turn into oligodendrocytes; it's often done by exposing these cells to a protein called Sonic Hedgehog, which produces oligodendrocytes in the spinal cord of developing embryos. Now Su-Chun Zhang and his co-workers show in the May issue of Development that treating human ES cells with this same protein also turns them into oligodendrocytes they just take longer to do it, 14 weeks as opposed to the 2 weeks taken by mouse ES cells. They also report another difference between mouse and human ES cells: a growth factor called Fgf2 that promotes oligodendrocyte development in mouse ES cells actually stalls it in human ES cells. As Dr Zhang reveals, these findings were quite unexpected. 'This was quite a surprise given that this is exactly how we direct mouse ES cells to become oligodendrocytes. But we have discovered an unexpected twist in the cell's response to the same external factor', explained Dr Zhang. 'It nevertheless explains why so many research groups have failed to persuade human neural stem cells to become oligodendrocytes for the past decade.' As Dr Zhang went on to discuss, these findings are also of clinical importance. 'We are now able to generate a relatively enriched population of oligodendrocyte precursor cells that may be used to repair lost myelin sheaths. These findings also raise awareness of the direct translatability of animal studies to human biology. In this regard, the human oligodendrocytes generated from human ES cells or the generation of disease-induced pluripotent stem cells can provide a useful tool in the future for screening pharmaceuticals directly on human cells.' The authors are from the Departments of Anatomy and Neurology at the School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, USA. They are funded by the National Institute of Neurological Disorders and Stroke and The National Multiple Sclerosis Society.

Science News New Possibility of Reversing Damage Caused by Multiple Sclerosis Dec. 6, 2010 Damage caused by multiple sclerosis could be reversed by activating stem cells that can repair injury in the central nervous system, a study has shown. Researchers from the Universities of Cambridge and Edinburgh have identified a mechanism essential for regenerating insulating layers known as myelin sheaths -- that protect nerve fibres in the brain. In additional studies in rodents, they showed how this mechanism can be exploited to make the brain's own stem cells better able to regenerate new myelin.

In multiple sclerosis, loss of myelin leads to the nerve fibres in the brain becoming damaged. These nerve fibres are important as Theky send messages to other parts of the body. The scientists believe that this research will help in identifying drugs to encourage myelin repair in multiple sclerosis patients. Professor Robin Franklin, Director of the MS Society's Cambridge Centre for Myelin Repair at the University of Cambridge, said: "Therapies that repair damage are the missing link in treating multiple sclerosis. In this study we have identified a means by which the brain's own stem cells can be encouraged to undertake this repair, opening up the posibility of a new regenerative medicine for this devastating disease." The study, funded by the MS Society in the UK and the National Multiple Sclerosis Society in America, is published in Nature Neuroscience. Professor Charles ffrench-Constant, of the University of Edinburgh's MS Society Centre for Multiple Sclerosis Research, said: "The aim of our research is to slow the progression of multiple sclerosis with the eventual aim of stopping and reversing it. This discovery is very exciting as it could potentially pave the way to find drugs that could help repair damage caused to the important layers that protect nerve cells in the brain." Multiple sclerosis affects almost 100,000 people in the UK and several million worldwide. It often targets young adults between the ages of 20 and 40.