Prof Franklinstein suggests age is a problem

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Why do we do this?

Well a few years ago the collaborators of Prof Franklin sewed a young and an old mouse together and gave the old mouse a young mouse’s blood supply. This gruesome experiment is called parabiosis and is frowned upon in the UK as unacceptable science…The stress of the procedure must be horrendous. Imagine being sewn to a bully who is going to torment you…or imagine being stitched to a pervert. However, Mary Shelly would have been proud of this as she created a monster.

You don’t repair as well when you are older and this is shown again,

Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination.Rivera FJ, de la Fuente AG, Zhao C, Silva ME, Gonzalez GA, Wodnar R, Feichtner M, Lange S, Errea O, Priglinger E, O’Sullivan A, Romanelli P, Jadasz JJ, Brachtl G, Greil R, Tempfer H, Traweger A, Bátiz LF, Küry P, Couillard-Despres S, Franklin RJM, Aigner L. Glia. 2019 Apr 30. doi: 10.1002/glia.23624. [Epub ahead of print]. Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that leads to severe neurological deficits. Due to their immunomodulatory and neuroprotective activities and their ability to promote the generation of oligodendrocytes, mesenchymal stem cells (MSCs) are currently being developed for autologous cell therapy in MS. As aging reduces the regenerative capacity of all tissues, it is of relevance to investigate whether MSCs retain their pro-oligodendrogenic activity with increasing age. We demonstrate that MSCs derived from aged rats have a reduced capacity to induce oligodendrocyte differentiation of adult CNS stem/progenitor cells. Aging also abolished the ability of MSCs to enhance the generation of myelin-like sheaths in demyelinated cerebellar slice cultures. Finally, in a rat model for CNS demyelination, aging suppressed the capability of systemically transplanted MSCs to boost oligodendrocyte progenitor cell (OPC) differentiation during remyelination. Thus, aging restricts the ability of MSCs to support the generation of oligodendrocytes and consequently inhibits their capacity to enhance the generation of myelin-like sheaths. These findings may impact on the design of therapies using autologous MSCs in older MS patients.

Well you can all read and suggests doom and gloom for older people and that has been seen to be an issue with anti-LINGO-1 antibody where people who are younger respond to treatment.

Does that spell bad news for older people? Well the good news is that you can get rejuvenated or should I say your phagocytes can as they have to hoover-up the debris before repair can occur. How do you you do it. Well there is more than one way to achieved this and ProfF has their own way of doing it. It has been spoken about but I’ll wait until it is published before I say more.

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12 comments

  • Wow, Ocrelizumab gets a license for PPMS treatment in England and this blog says nothing about it.

    Utter tosh this blog is. It’s now just an ego-ride for has-been clinicians who’ve delivered too little.

    • Prof Franklin wants to do a trial with Clemastine Fumarate + Metformin, for similar reasons
      https://www.youtube.com/watch?v=VgHi4JjKVwA (at 33′)

      This is a report from a patient that has tried the combination (not me). Cannot confirm any of the below: “After seeing this, I started on Metformin with Clemastine a few weeks ago. I know this sounds unlikely, but I seem to be seeing changes already. I have had MS for more than 20 years and am in a poor state of health. However, for the last week, I have been able to get in and out of bed without assistance. Before starting the Metformin, I hadn’t been able to into bed unaided for several months and I hadn’t been able to get up in the morning unaided for something like a year. Other things are improving too, which is something I’ve never seen, since being diagnosed with MS, even though I’ve been on powerful DMTs.”

      Also a discussion https://community.mssociety.org.uk/forums/everyday-living/symptoms-improving-after-starting-metformin-and-clemastine

      • Thank you for this but I am afraid this can not be used as evidence. Whilst I am not questioning peoples feelings after all it is your body, but we have been here before where people take things and claim/feel benefit only for trials to be done and no sustainable benefit is found. Is it the metformin?, the clemestine or a combination of the metformin and clemastine?

        This post was made on MS Society the 17 June 2018 we are now a year on.

        Is this a way to say that the Bexarotene trial has failed?

        • Of course, its anecdotal, but the consept has some reasoning and Metformin has a great potential, yet its a cheap as chips generic and one has to really push to do the trial and get these answers.

  • It seems that humans are diferent than mouse

    To determine whether donor characteristics influence the growth of MSCs, we measured the PDT of MS-derived
    MSCs (n=47) compared to non-MS controls (n=5). We found no correlation between PDT and disease duration,
    donor age, or disease subtype. Furthermore, donor characteristics had no impact on the yield of MSC-NPs
    generated. Transcriptional profiling of MSC/MSC-NP pairs demonstrated upregulation of gene candidates that
    mediate trophic/immunoregulatory mechanisms of action of MSC-NPs.
    Conclusions:
    Characterization of the transcriptional profile of MSC-NPs has revealed potential pathways that mediate
    therapeutic mechanisms of this novel cell therapy in MS.

    Transcriptional Profiling of Autologous B
    one Marrow Mesenchymal Stem Cell-Derived
    Neural Progenitors (MSC-NPs) from Patients with Multiple Sclerosis

    http://indexsmart.mirasmart.com/AAN2019/PDFfiles/AAN2019-001540.pdf

  • This study argues otherwise

    Human mesenchymal factors induce rat hippocampal- and
    human neural stem cell dependent oligodendrogenesis

    We present data which provides evidence that intrinsic oligodendroglial
    differentiation mechanisms of parenchymal precursor- and
    neural stem cells differ but that extrinsic (MSC-derived) stimuli are not
    restricted to specific stages or ages. Moreover, we show for the first
    time that also fetal human MSC-derived factors are equally potent in
    stimulating oligodendrogenesis and in preventing astrocyte formation
    and that they can potently instruct human induced pluripotent stem
    cell-derived NSCs. Our findings can thus contribute to the overall
    understanding of instructive stem/stem cell interactions and to the
    possible development of future myelin repair strategies.

    DOI: 10.1002/glia.23233

  • Response to theraphy

    Phase I/II Clinical Trials Testing Multiple
    Dosing of Intrathecal Mesenchymal Stem Cell-
    Derived Neural Progenitors in Patients with Progressive MS

    Results:
    Eight of the 20 subjects in the phase I trial showed EDSS improvements (range 0.5 to 3.5 point improvement)
    after 12 months. The 30 month follow-up in 18 out of 20 subjects demonstrated that 7 subjects (39%) showed
    continued sustained improvement in EDSS. One subject who had previously demonstrated 1.0 improvement,
    demonstrated slight worsening in year 2
    .
    In the remaining subjects, 33% had continued stable EDSS, and 22%
    showed continued disease progression. These results suggest that additional treatments may be required to
    sustain the full effect of IT-MSC-NP treatment. A phase II trial is underway to investigate the safety and efficacy of
    6 separate IT-MSC-NP treatments compared to a placebo IT-saline control.

    http://indexsmart.mirasmart.com/AAN2019/PDFfiles/AAN2019-001623.pdf

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