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Member
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Join Date: Jan 2008
Location: Maryland outside WASH DC
Posts: 258
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Member
Join Date: Jan 2008
Location: Maryland outside WASH DC
Posts: 258
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Quote:
Originally Posted by Bentnub
Neurologische Universitätsklinik, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany.
Axonal destruction and neuronal loss occur early during multiple sclerosis, an autoimmune inflammatory CNS disease that frequently manifests with acute optic neuritis. Available therapies mainly target the inflammatory component of the disease but fail to prevent neurodegeneration. To investigate the effect of minocycline on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the optic nerve, we used a rat model of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis. Optic neuritis in this model was diagnosed by recording visual evoked potentials and RGC function was monitored by measuring electroretinograms. Functional and histopathological data of RGCs and optic nerves revealed neuronal and axonal protection when minocycline treatment was started on the day of immunization. Furthermore, we demonstrate that minocycline-induced neuroprotection is related to a direct antagonism of multiple mechanisms leading to neuronal cell death such as the induction of anti-apoptotic intracellular signalling pathways and a decrease in glutamate excitotoxicity. From these observations, we conclude that minocycline exerts neuroprotective effects independent of its anti-inflammatory properties. This hypothesis was confirmed in a non-inflammatory disease model leading to degeneration of RGCs, the surgical transection of the optic nerve.
PMID: 17239606 [PubMed - indexed for MEDLINE]
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THANKS!
Targeting "things" to reduce BOTH Inflammation and glutamate excitotoxicity makes a lot of sense.
I am not a fan of minocycline treatment because I feel that it's main benefit comes from reducing MMP-9s and the damage the MMP-9s do in the MS's destructive processes. I have been researching safe ways to reduce glutamate excitotoxicity via a number of common supplements.
I hope you realize that it is NOT the antibiotic nature of minocycline that provides its MS benefit. I would not take it or recommend taking it for a long period of time. There are better & safer alternatives.
jackD
Quote:
Breakthrough in research for multiple sclerosis (MS)
28 Oct 2004
Paratek Pharmaceuticals, Inc announced results of preclinical studies demonstrating that a new class of compounds, orally available non-antibacterial tetracyclines, has shown promising activity in a preclinical animal model of multiple sclerosis (MS). Affecting approximately 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. David McKenney, a Paratek scientist, will present the findings during an oral presentation at 2:30 p.m. PST (5:30 p.m. EST) today at Neuroscience 2004, the Society for Neuroscience's 34th Annual Meeting in San Diego.
For the first time, Paratek is presenting data showing that its non-antibacterial tetracycline compounds in a preclinical model of MS have efficacy comparable to minocycline, an antibiotic also in the tetracycline family. A previous clinical study directed by Dr. Luanne Metz at the University of Calgary has demonstrated disease protection in MS patients treated with minocycline. Unfortunately, long-term treatment with minocycline or any other broad-spectrum antibiotics causes many patients to experience intolerability related to antibiotic side effects. In today's presentation, Paratek will report that three non-antibacterial tetracycline compounds, with different structures, demonstrated activity in reducing limb paralysis in the preclinical EAE (Experimental Autoimmune Encephalomyelitis) model of MS. These compounds have 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 modifying treatment for multiple sclerosis (MS). The agreement covers the compounds for which Dr. McKenney presents data today.
Stuart Levy, Paratek's Vice Chairman, Chief Scientific Officer and Co-Founder, commented, "The clinical research community has long regarded a pill for MS as an ultimate goal, but so far attempts to develop a safe, feasible, orally available drug candidate have failed. Our team has successfully modified the tetracycline molecule, keeping the core structure that confers anti-MS activity while removing portions of the molecule with antibacterial effects. This represents an exciting advance not only for MS, but potentially for many other inflammation-related disease areas. "
Dr. Michael Draper, Associate Director at Paratek, stated, "Paratek has developed 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 of non-antibacterial tetracycline compounds will avoid the negative consequences associated with long-term antibiotic use and will not further contribute to the development of antibiotic resistance. We believe that these highly active, orally available compounds will also prove to be well-tolerated for MS, and we are very proud of this accomplishment."
About Multiple Sclerosis
Multiple sclerosis is a chronic, inflammatory condition of the nervous system and is the most common non-traumatic neurological disease in young adults. Multiple sclerosis may affect approximately two million people worldwide. While symptoms can vary, the most common symptoms of multiple sclerosis include blurred vision, numbness or tingling in the limbs and problems with strength and coordination. The relapsing forms of multiple sclerosis are the most common.
About Paratek Pharmaceuticals
Paratek Pharmaceuticals, Inc. is engaged in the discovery and commercialization of new therapeutics that treat serious and life-threatening diseases, with a particular focus on the growing worldwide problem of antibiotic resistance. Paratek's lead programs are advancing novel compounds that can circumvent or block bacterial resistance, as well as drugs that can prevent infection by interfering with Multiple Adaptational Response (MAR) mechanisms in bacteria. Out of these efforts, Paratek has discovered a new class of antibiotics, the aminomethylcyclines that target the need for new and potent antibacterials to overcome the problem of rapidly growing bacterial resistance. The Company's lead antibiotic clinical candidate, BAY 73-7388, the first product from this class, is being developed in a collaborative partnership with Bayer HealthCare AG for the treatment of serious infections.
Outside the antibacterial therapeutic area, Paratek has also established an internal effort to exploit its novel families of compounds and their unique mechanism of action in selected anti-inflammatory and neurodegenerative conditions. Paratek has an active chemical synthesis effort to produce novel and diverse small molecules, with the goal of developing non-antibacterial products with improved activity in serious diseases based upon a growing body of clinical and basic research supporting this approach.
Paratek is privately held and headquartered in Boston, Massachusetts, USA. For more information, visit Paratek's website at http://www.paratekpharm.com
Multiple Sclerosis - Paratek is developing orally available non-antibacterial tetracyclines for the treatment of multiple sclerosis (MS). These compounds are disease modifying agents to reduce demyelination, relapses and progression in patients suffering from various forms of MS, including relapsing and remitting MS. This effort follows the recent publication of very favorable clinical data with minocycline (reference 26). Paratek’s novel compounds offer the potential to show improved activity but without the side effects associated with broad spectrum antibiotics, which can be a problem with long-term use of minocycline. Paratek established a Collaborative Research and License Agreement with Serono SA in October 2004 to develop novel and improved tetracycline derived compounds for MS. Paratek presented data on its novel non-antibacterial tetracycline derivatives in the EAE model in October 2004 Lead candidate compounds for preclinical development are expected to be designated by mid 2006.
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The second stage of MS -THE NEURODEGENERATIVE STAGE - where the excess glutamate kills neurons.
http://home.ix.netcom.com/~jdalton/ms-two-stages.pdf
Below pic/chart is from this report. NOTE EXCESS GLUTAMATE
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