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Important discovery that increases understanding of multiple sclerosis15 Sep 2004http://www.medicalnewstoday.com/newssearch.php?newsid=13430Scientists at the University of California, Santa Barbara have made animportant discovery that will increase the understanding of multiplesclerosis, a debilitating disease of the central nervous system in whichthe myelin sheath, an insulating membrane surrounding the nerve cells inthe brain and spinal cord, start to unravel for reasons as yet unknown.In a paper appearing in today's issue (Sept. 14) of the Proceedings ofthe National Academy of Science, several UC Santa Barbara researchersdescribe the results of a study that shows why the unraveling occurs.The myelin sheath is made up of a lipid bilayer (similar to those makingup the cell membrane) wrapped many times around the nerve axon -- thepart of a nerve cell through which impulses travel away from the cellbody.One specific protein, called myelin basic protein, acts to hold themyelin sheath together tightly around the axon. The axons serve as theelectrical wires that connect the nerve cells, and the myelin serves asthe insulation to keep the electrical impulses flowing quickly andreliably."If the myelin breaks down, for whatever reason, the nerve electricalimpulses leak out, slow down, and generally don't work very well," saysJoe Zasadzinski, professor of chemical engineering at UCSB.Zasadzinski, with co-authors Israelachvili, professor of chemicalengineering, graduate student Yufang Hu and postdoctoral fellow IvoDoudevski, and Husted, director of UCSB's Center for the Studyof Neurodegenerative Disorders write that "We have discovered that inthe progression of MS, there are small changes in the lipid compositionof myelin. There is less negatively-charged lipid in the membrane andmore neutral, or uncharged, lipids. Myelin basic protein is positivelycharged and gets in between the bilayers to link up thenegatively-charged lipids and glue the myelin sheath together."The scientists explain that the tightest seal occurs when the amount ofnegative charge from the lipids just match the amount of positive chargefrom the protein. If there is too much of either one, then the bilayersstart to repel each other rather than bind."Although we can't say why the lipid composition changes, now with thisnew knowledge, perhaps we can suggest methods of trying to treat theunraveling before it gets too far along," Zasadzinski says. Zasadzinski,Husted and Israelachvili also discovered that the myelin basic proteinacts as a patch to fill in any holes in the myelin bilayers. "It issimilar to the stuff you put in your tires to fix punctures,"Zasadzinski explains. "The myelin basic protein floats around until itfinds a hole, binds to the edge of the hole and then pushes the lipidsto fill in the hole, insuring good insulation from the myelin sheath."Joe Zasadzinski can be reached at 805-893-4769 Orgorilla@...Contact: Joan Magruderjoan.magruder@...805-893-3071University of California - Santa Barbarahttp://www.medicalnewstoday.com/newssearch.php?newsid=15540Paratek'>http://www.medicalnewstoday.com/newssearch.php?newsid=13430http://www.medicalnewstoday.com/newssearch.php?newsid=15540Paratek Pharmaceuticals, Inc announced results of preclinical studiesdemonstrating that a new class of compounds, orally availablenon-antibacterial tetracyclines, has shown promising activity in apreclinical animal model of multiple sclerosis (MS). Affectingapproximately two million people worldwide, MS is a chronic,inflammatory condition of the nervous system and the most common,non-traumatic, neurological disease in young adults. Dr. McKenney,a Paratek scientist, will present the findings during an oralpresentation at 2:30 p.m. PST (5:30 p.m. EST) today at Neuroscience2004, the Society for Neuroscience's 34th Annual Meeting in San Diego.For the first time, Paratek is presenting data showing that itsnon-antibacterial tetracycline compounds in a preclinical model of MShave efficacy comparable to minocycline, an antibiotic also in thetetracycline family. A previous clinical study directed by Dr. LuanneMetz at the University of Calgary has demonstrated disease protection inMS patients treated with minocycline. Unfortunately, long-term treatmentwith minocycline or any other broad-spectrum antibiotics causes manypatients to experience intolerability related to antibiotic sideeffects. In today's presentation, Paratek will report that threenon-antibacterial tetracycline compounds, with different structures,demonstrated activity in reducing limb paralysis in the preclinical EAE(Experimental Autoimmune Encephalomyelitis) model of MS. These compoundshave no detectable antibacterial activity.Paratek Pharmaceuticals, Inc. and Serono (virt-x: SEO and NYSE: SRA)announced today that they have entered into an agreement to discover,develop and commercialize an orally-available disease modifyingtreatment for multiple sclerosis (MS). The agreement covers thecompounds for which Dr. McKenney presents data today.Stuart Levy, Paratek's Vice Chairman, Chief Scientific Officer andCo-Founder, commented, "The clinical research community has longregarded a pill for MS as an ultimate goal, but so far attempts todevelop a safe, feasible, orally available drug candidate have failed.Our team has successfully modified the tetracycline molecule, keepingthe core structure that confers anti-MS activity while removing portionsof the molecule with antibacterial effects. This represents an excitingadvance not only for MS, but potentially for many otherinflammation-related disease areas. "Dr. Draper, Associate Director at Paratek, stated, "Paratek hasdeveloped world-class expertise in modifying the tetracycline class,which has a 30-year track record in the marketplace and a favorable,well-documented safety profile. This new, proprietary class ofnon-antibacterial tetracycline compounds will avoid the negativeconsequences associated with long-term antibiotic use and will notfurther contribute to the development of antibiotic resistance. Webelieve that these highly active, orally available compounds will alsoprove to be well-tolerated for MS, and we are very proud of thisaccomplishment."About Multiple SclerosisMultiple sclerosis is a chronic, inflammatory condition of the nervoussystem and is the most common non-traumatic neurological disease inyoung adults. Multiple sclerosis may affect approximately two millionpeople worldwide. While symptoms can vary, the most common symptoms ofmultiple sclerosis include blurred vision, numbness or tingling in thelimbs and problems with strength and coordination. The relapsing formsof multiple sclerosis are the most common.About Paratek PharmaceuticalsParatek Pharmaceuticals, Inc. is engaged in the discovery andcommercialization of new therapeutics that treat serious andlife-threatening diseases, with a particular focus on the growingworldwide problem of antibiotic resistance. Paratek's lead programs areadvancing novel compounds that can circumvent or block bacterialresistance, as well as drugs that can prevent infection by interferingwith Multiple Adaptational Response (MAR) mechanisms in bacteria. Out ofthese efforts, Paratek has discovered a new class of antibiotics, theaminomethylcyclines that target the need for new and potentantibacterials to overcome the problem of rapidly growing bacterialresistance. The Company's lead antibiotic clinical candidate, BAY73-7388, the first product from this class, is being developed in acollaborative partnership with Bayer HealthCare AG for the treatment ofserious infections.Outside the antibacterial therapeutic area, Paratek has also establishedan internal effort to exploit its novel families of compounds and theirunique mechanism of action in selected anti-inflammatory andneurodegenerative conditions. Paratek has an active chemical synthesiseffort to produce novel and diverse small molecules, with the goal ofdeveloping non-antibacterial products with improved activity in seriousdiseases based upon a growing body of clinical and basic researchsupporting this approach.Paratek is privately held and headquartered in Boston, Massachusetts,USA. For more information, visit Paratek's website athttp://www.paratekpharm.com.Contact: Compakcompa@...212-213-0006Burns McClellanhttp://www.medicalnewstoday.com/newssearch.php?newsid=15540