Tuesday, 9 December 2014

Glatiramer acetate improves memory loss.......in mice

LoPresti P. Glatiramer Acetate Guards Against Rapid Memory Decline During Relapsing-Remitting Experimental Autoimmune Encephalomyelitis.Neurochem Res. 2014 Dec 7. [Epub ahead of print]

Cognitive decline presents a therapeutic challenge for patients with multiple sclerosis (MS), a disease characterized by recurrent autoimmune demyelination and by progressive CNS degeneration. Glatiramer acetate (GA, also known as Copolymer 1, Cop-1, or Copaxone), commonly used to treat MS, reduces the frequency of relapses; it has both anti-inflammatory and neuroprotective properties. However, clinical trials have not definitively shown that GA improves cognitive impairment during MS. Using an in vivo animal model of autoimmune demyelination, i.e., relapsing-remitting experimental autoimmune encephalomyelitis (EAE), we tested short-term memory in EAE mice (EAE), in EAE mice treated with GA for 10 days starting at the time of immunization (EAE + GA), and in age-matched healthy, naïve mice (Naïve). Short-term memory was assessed using the cross-maze test at 10, 20, and 30 days post-immunization (d.p.i.); data were analyzed at each time point and over time. At 10 d.p.i., EAE and EAE + GA mice had better memory function than Naïve mice. However, at the later time points, EAE mice had a steep negative slope of memory function (indicating decline), whereas EAE + GA mice had a flatter, less-negative slope of memory function. Notably, the memory function of EAE mice significantly decreased over time compared with that of Naïve mice, indicating that EAE had a negative impact on cognitive ability. In contrast, there was no statistically significant difference between the slopes of memory function in mice with EAE treated with GA versus Naïve mice, which revealed effective, albeit partial, protection by GA treatment against progressive memory decline during EAE disease. Of particular interest, although EAE mice had memory decline over 30 d.p.i., their clinical disease scores improved during that time. Thus, our results suggest that EAE mice had a significant progressive memory decline and that GA, administered at the time of immunization, partially guards against rapid memory decline.



We know that GA has more mechanisms of action than peas in a pod and now the EAEers tells us that it stops Cognitive decline. 

So in this study the mouse remembers a maze and moves through it to get the reward. However, when they get EAE the get nerve problems and they don't remember too well.

So stop EAE with GA and you don't get the nerve damage and so the mice remember better....Go figure.

So if EAE causes pain and GA stops EAE then GA stops pain and on and on and on and on....Chicken and Egg

If animals can't move well then they wont do too well in tests that require movement but it is also the case that it takes a few days for the results of the inflammatory response to develop into nerve loss so animals could have improved  movement due to problems in the spinal cord that are not in sync with brain problems. 

If clinical studies do not show that GA improves cognitive decline, should we care what happens in the humble mouse? 
So much for 3Rs. Maybe you find this type of info useful?

4 comments:

  1. You're so right MD, who cares what happens in the humble mouse model EAE. Copaxone has been around for a long time > 20 years, to still do this kind of research on mice is frivolous, hopefully pharma took care of him. The publishing journal must be starved for publications.

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    1. Amen, I thought that it was proven that the mouse model is no good for testing the EAE pretend disease on? Also I have read many studies including one from UBC that discredits the first generation of drugs, including Copaxone?
      I am now confused as I do read your blog regularly but still we are reading about drugs that cost a fortune and have been proven Not to make a difference in the out come of MS for the long term?
      I think Dr. Ebbers said it well!! And he is a neurologist.. Thank You for all your hard work and contributions, time for better testing and a new model of MS.

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    2. EAE is no good for testing pretend disease.
      I disagree it....and yes I am biased so take no notice, as many of you will. animal models have their part to play and I could cite a host of studies that show that beta interferons and GA are not the bees knees they are cracked up to be. Remember they are not the bees knees in MS either. Likewise the regulatory agencies such as NICE have reported that the first line drugs are not cost effective.

      These "placebo plus" drugs :-) serve a purpose and do alright for some people. However we have moved forward and it is now the case that there are even more effective drugs for MS. We report on drugs and they cost a fortune and they are effective at what thy do, that is stop or slow the occurrence of relapse. This is proven. What is not know is the longer-term effects.

      There is a number of people that think that "Prof Ebers said it well as a neurologist" that relapses don't matter. This was used by the CCSVI fanatics to justify the anti-drug stance that the likes of Dr. Dre I believe supports.

      As a basic scientist I can say that Prof Ebers is retired. Maybe ProfG will meet him in Canada this week.

      We live in a different world of markedly more effective drugs and not just the realms of placebo plus or no treatments on which the original thoughts were based.

      As I have said many times, tell the person who has been left disabled by a relapse, that they don't matter. They clearly do and are best avoided

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    3. P.S. With glaterimer acetate in animals you can make it work very well or not so well depending how and when you give it. Likewise you can make fingolimod work very well or not so very depending on how and when you give it.

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