LINGO-1 In MIce improves Memory

Sun JJ, Ren QG, Xu L, Zhang ZJ.LINGO-1 antibody ameliorates myelin impairment and spatial memory deficits in experimental autoimmune encephalomyelitis mice. Sci Rep. 2015 Sep 18;5:14235. doi: 10.1038/srep14235.

More than 50% of multiple sclerosis patients develop cognitive impairment. However, the underlying mechanisms are still unclear, and there is no effective treatment. LINGO-1 (LRR and Ig domain containing NOGO receptor interacting protein 1) has been identified as an inhibitor of oligodendrocyte differentiation and myelination. Using the experimental autoimmune encephalomyelitis (EAE) mouse model, we assessed cognitive function at early and late stages of EAE, determined brain expression of myelin basic protein (MBP) and investigated whether the LINGO-1 antibody could restore deficits in learning and memory and ameliorate any loss of MBP. We found that deficits in learning and memory occurred in late EAE and identified decreased expression of MBP in the parahippocampal cortex (PHC) and fimbria-fornix. Moreover, the LINGO-1 antibody significantly improved learning and memory in EAE and partially restored MBP in PHC. Our results suggest that demyelination in the PHC and fimbria-fornix might contribute to cognitive deficits and the LINGO-1 antibody could ameliorate these deficits by promoting myelin growth in the PHC. Our research demonstrates that LINGO-1 antagonism may be an effective approach to the treatment of the cognitive impairment of multiple sclerosis patients.

Anti-LINGO-1 is in trial in MS for repair. Will it work? We have to wait and see. What does it do in MS?. It promotes repair, which is great. So I know you like hear about remyelination

This is a repeat study using another antibody and in this study control animals have a wobbly gait and Lingo-1 treatment means they are more or less normal. 

So if there is more myelin in Lingo-1 treated animals, is it because they had less demyelination or is it really more repair. Also is it better memory or is it because they have accumulated less deficit they can move more and so do better in the memory tests that involve movement. You can make up your own mind as it is open source. However these are the questions  you need to ask, if you are to understand the data.

However, the clinical course seen looks like that found with Biogen study with anti-LINGO-1, so we could say great.

LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis.Mi S, Hu B, Hahm K, Luo Y, Kam Hui ES, Yuan Q, Wong WM, Wang L, Su H, Chu TH, Guo J, Zhang W, So KF, Pepinsky B, Shao Z, Graff C, Garber E, Jung V, Wu EX, Wu W. Nat Med. 2007;13(10):1228-33.

We have done interpreting EAE in post posts, so the question one should be posing is: Was there any damage and demyelination in the first place? Is this treatment anti-inflammatory that stops inflammation accumulating so there are no signs?. if so how. 

Surely if the the agent was only causing remyelination be would first see damage and therefore clinical disease and the control and test should be the same before better recovery in the treated group.

Maybe we need to know what happens when treatment is started after demyelination has long occurred. Because this could influence the type of trial to do in MS. In this scenario , we should give anti-Lingo at the time of relapse to promote a faster recovery. But what we probably want to know is that if we have established demyelination can we repair it. Because if we do this in MS and it fails…we blame the EAE but would that be justified?

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  • Huuum … I hope it works the realization of human trials as well as it did in EAE; being realistic we know that the "conversion" in general is not the same … I also wanted to Anti Lingo-1 would be used as a combination treatment combined with a DMT and a neuroprotective. And if he would have the ability to promote remyelination of old injuries. As I understand the study in EAE seems so … Fingers crossed for it to work …

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