Saturday, 17 May 2014

Crippled Mice Walk again... a Miracle Cure?

This is the headline from the Independent Newspaper and whatever the real story this is not going to completely real and is the stuff of false hopes and pretty poor reporting

This story relates to a viral model of MS, where mice were injected with a hepatitis virus in the brain and causes demyelination and after 14 days when disease was present they injected human neural stem cells (they can make nerves oligodendrocytes and astrocytes) in the spine and disease went away more or less and it didn't come back yet the stem cells could not be found within a couple of weeks. This process induced T regulatory cells to suppress inflammation but the virus did not cause disease again in the "cured" mice...had it already been eliminated? In this study 70% recovered verses about 15% that recovered but did not get anything. There was a promotion of remyelination. In EAE these types of cells have been used and whilst they offer some protection, it is not a cure. 

As is common in all types of these studies the cells appear to work by providing growth factors and do not appear to becoming new cells. The stem cells are clearly not becoming new nerves or myelinating cells and probably are promoting natural repair processes. 

So it you have lost nerves and have disability because of this then they did not show that this is reversed. So the obvious experiment would have been to let disability to become long established and then see if they could recover the function.

In the newspaper the authors are quoted as saying the animals were so sick they could not eat or drink  and had to be hand fed, they got the cells and recovered.....great. However, it is interesting that they kept such control animals for 5 months doing nothing.... except being very sick....all to create a straight line on a graph to keep it pretty........yuck.

The paper is open source so you can read it yourself  (click here

This is encouraging but a cure call me sceptical and so should you be.





Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis

Highlights

  • Spinal cord transplantation of hNPCs results in recovery in a viral model of MS
  • hNPC-mediated recovery occurs in the absence of engrafted cells
  • hNPCs are immunomodulatory through increasing the frequency of Tregs in the CNS
  • hNPCs increase Treg frequency via a TGF-β1- and TGF-β2-dependent pathway

Summary

Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4+CD25+FOXP3+ regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.

8 comments:

  1. Re: "In EAE these types of cells have been used and whilst they offer some protection, it is not a cure.

    Neither is alemtuzumab.

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    Replies
    1. True it is not cure but in a head to head its effects are much more impressive

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  2. Not sure why anyone does any work on mice any more. Such a waste of time and money. Money that could be spent on phase 3 statin trials

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  3. Firstly, the press once again is using catch phrases such as "miracle cure" to sell copy. The authors are not implying cure but are stating that hNPCs transplanted via intraspinal injection alter the microenvironment via secreted factors, specifically TGF-B1/B2. The result: promoting increased T-regs (CD4+ CD25+ FOXP3+). The authors state: "it is unlikely that transplanted hNPCs were differentiating into oligos, it appears that remyelination is occurring in response to activation of endogenous OPCs thru mechanisms that remain to be defined." Intrathecal injection of hNPCs could alter the microenvironment from pro-inflammatory to reduced inflammation via Tregs and increased endogenous repair. It is interesting that the transplanted cells did not need to survive in order to promote secretion of the beneficial factors. Will this be sustained in the long term? The authors seem to think that increased Tregs occurring after hNPCs disappeared and is sustainable. Will cell free therapies be necessary or will the identification of the secreted factors be necessary to provide long term benefits?

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    Replies
    1. I suspect the press office is the problem as other reports have the same rhetoric i am sure the authors were not behinx the media hype. As a recipient of the powers of the press it is seldom the researchers that make the claims

      Delete
  4. http://www.scripps.edu/newsandviews/e_20140519/loring.html
    Here's the link to the Scripps Research site regarding the study.

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  5. To all our new viewers from the Independent...I say welcome.....
    You however need to be more discerning about what comments you read and take notice of.

    ReplyDelete

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