A paper from Sriram and Steiner criticizing EAE

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A paper from Sriram and Steiner criticizing EAE

Postby dignan » Sat Dec 10, 2005 10:53 am

Look, it's an article from a well-known researcher (Dr Sriram) slamming the use of EAE as a model in MS! It's good to see.



Experimental allergic encephalomyelitis: A misleading model of multiple sclerosis.

Ann Neurol. 2005 Dec;58(6):939-45.
Sriram S, Steiner I.
Department of Neurology Vanderbilt Medical Center, Nashville, TN.

Despite many years of intensive research, multiple sclerosis (MS) defies understanding and treatment remains suboptimal. The prevailing hypothesis is that MS is immune mediated and that experimental allergic encephalomyelitis (EAE) is a suitable model to elucidate pathogenesis and devise therapy.

This review examines critically the validity that EAE is an adequate and useful animal model of MS and finds credible evidence lacking. EAE represents more a model of acute central nervous system inflammation than the counterpart of MS.

We propose to reconsider the utilization of EAE, especially when this model is used to define therapy. This will also force us to examine MS without the restraints imposed by EAE, as to what it is, rather than what it looks like.

Ann Neurol 2005;58:939-945.

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Misleading indeed!

Postby SarahLonglands » Sun Dec 11, 2005 4:31 pm

A very good paper co-authored by Ram Sriram from Vanderbilt and Israel Steiner from Jerusalem. I saw the full paper prior to publication and it is well worth the read for anyone who can get hold of it.

Sarah :wink:
An Itinerary in Light and Shadow Completed Dr Charles Stratton / Dr David Wheldon abx regime for aggressive secondary progressive MS in June 2007, after four years. Still improving with no relapses since starting. Can't run but can paint all day.
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Re: A paper from Sriram and Steiner criticizing EAE

Postby HarryZ » Sun Dec 11, 2005 5:39 pm

Dignan,

A couple of years ago, Dr. P.O. Behan wrote his Pathogenesis of MS and stated that the EAE model was pretty much useless in trying to correlate what happened in that poor mouse to what took place in human MS patients. He went on to say that there has never been one treatment that worked in the "mouse" that had any benefit to humans.

I guess this is another reason why MS research progression has been quite abysmal over the years.

Harry
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Re: A paper from Sriram and Steiner criticizing EAE

Postby NHE » Sun Dec 11, 2005 11:35 pm

Several of the papers that I've read recently using the EAE mouse model have made reference to the SJL/J mouse. Below is a description of the SJL/J phenotype provided by Jackson Laboratories. The description is particularly interesting to read. It seems that these mice are really screwed up. Not only do they have a high susceptibility to EAE, but they also develop prolific cancers as well as spontaneous myopathy making it a model for muscular dystrophy. It does make one wonder if when this mouse is found to benefit from treatments for EAE, that it's actually also deriving some benefit for its other problems as well.

SJL/J
Strain Former & Common Name(s): SJL; Swiss Jim Lambert
Important Note: This strain is homozygous for the retinal degeneration allele Pde6b rd1. Stock Number 000686
Application(s) Autoimmunity (experimental allergic encephalomyelitis (EAE))
Additional Research Areas
Cancer Research; Cardiovascular Research; Diabetes and Obesity Research; Mouse/Human Gene Homologs; Research Tools; Sensorineural Research

Phenotype SJL mice display a very high incidence of reticulum cell sarcomas resembling Hodgkin’s disease around one year of age. Sarcomas first appear in the Peyer’s patches and mesenteric lymph nodes and later in the spleen, liver, thymus and other lymph nodes. Most of the tumors are mixed-cell types classified as type B reticulum cell neoplasms, but a few are type A histiocytomas. This strain is also characterized by extreme aggression in males and its susceptibility to experimental autoimmune encephalomyelitis (EAE) for multiple sclerosis research. SJL/J mice develop a spontaneous myopathy resulting from a splice-site mutation in the Dysferlin gene. This Dysf im allele has been shown to result in decreased levels of dysferlin protein in SJL/J mice and makes this strain a good model for limb girdle muscular dystrophy 2B. This spontaneous myopathy is characterized by a progressive loss of muscle mass and strength corresponding with an increase in muscle pathology including muscle fibers with central nuclei, variation in size, splitting, inflammatory infiltrate, necrosis, and eventual replacement of muscle fiber with fat. While muscle weakness can be detected as early as three weeks of age the greatest pathology occurs after 6 months of age. SJL/J mice have also been shown to have an increased rate of muscle regeneration after injury when compared to BALB/c mice. SJL mice, fed an atherogenic diet (1.25% cholesterol, 0.5% cholic acid and 15% fat), fail to develop atherosclerotic aortic lesions in contrast to several highly susceptible strains of mice (e.g. C57BL/6J, Stock No. 000664; C57L/J, Stock No. 000668, C57BR/cdJ, Stock No. 000667, and SM/J, Stock No. 000687). SJL/J are also useful as a control strain for studying immune defects in NOD/LtJ mice (Stock No. 001976), a model for type 1 diabetes (IDDM). Both NOD and SJL/J are derived from swiss mice; SJL are immunocompetent but have elevated levels of circulating T cells.


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