Friday, 10 June 2016

Cocktail of genes make stem cells reverse the damage

A triple-effect cocktail produced by neural stem cells as a novel neurorepair therapy for chronic stage CNS autoimmunity.
Li X, Zhang Y, Yan Y, Ciric B, Ma CG, Gran B, Curtis M, Rostami AM, Zhang GX. Mol Ther. 2016. doi: 10.1038/mt.2016.104. [Epub ahead of print]

Treatment of chronic neurodegenerative diseases such as multiple sclerosis (MS) remains a major challenge. Here we genetically engineer neural stem cells (NSCs) to produce a triply therapeutic cocktail comprising IL-10, NT-3, and LINGO-1-Fc, thus simultaneously targeting all mechanisms underlie chronicity of MS in the central nervous system (CNS): persistent inflammation (IL-10), loss of trophic support for oligodendrocytes and neurons (NT-3), and accumulation of neuroregeneration inhibitors (LINGO-1). After transplantation, NSCs migrated into the CNS inflamed foci and delivered these therapeutic molecules in situ. NSCs transduced with one, two, or none of these molecules had no or limited effect when injected at the chronic stage of experimental autoimmune encephalomyelitis; cocktail-producing NSCs, in contrast, mediated the most effective recovery through inducing M2 macrophages/microglia, reducing astrogliosis, and promoting axonal integrity and endogenous oligodendrocyte/neuron differentiation. These engineered NSCs simultaneously target major mechanisms underlying chronicity of MS and EAE, thus representing a novel and potentially effective therapy for the chronic stage of MS, for which there is currently no treatment.



This study suggests the trilogy of anti-inflammatory, nerve and oligodendrocyte survival factors can make neural stem cells work to recover function. This is what we want and that is repair. 

However, is there really added benefit of IL-10/NT-3 and anti-LINGO-1 over NT-3/LINGO-1 containing stem cells?

So genetically engineered cells are the way to go and according to this study neural stem cells do nothing to EAE. Whilst our results are not inconsistent with this, it argues against the efficacy claimed in other studies using un-manipulated neural stem cells. 

Here another published this week


Mesenchymal Stromal/Stem Cells Do Not Ameliorate Experimental Autoimmune Encephalomyelitis and Are Not Detectable in the Central Nervous System of Transplanted Mice. Abramowski P, Krasemann S, Ernst T, Lange C, Ittrich H, Schweizer M, Zander A, Martin R, Fehse B. Stem Cells Dev. 2016 Jun 1. [Epub ahead of print]

These are what is planned in humans and if this study is correct then the studies will fail. If the trials fail, enthusiasm for genetically engineered cells will be diminished. Indeed would we risk genetically engineering.

In this study the cells are administered over a month after the development of neurological disease and complete hindlimb paralysis is repaired so the animal is only left with a paralysed tail.

It would be great if this can be repeated, we can't do it because we are not allowed to have animals paralysed as long (3 months) as occurred here, as the vet thought it was not ethical..I guess they justified it.

I would expect that by a month after the attack the influence of inflammation would be resolved and immunotherapy would not work as we have found in a number of cases. Therefore it is absolutely amazing that nerve pathways can be resurrected this long after damaged was initiated.

Roll on repetition.

2 comments:

  1. Dear MD,

    These are my favorite kind of posts, roll on repetition indeed.

    ReplyDelete
  2. Wow, fantastic! Here's hoping someone actually bothers to try replicating the results, as you say! I wonder what a month in 'human years' = in 'mouse years'?

    ReplyDelete

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