Perspectives on new stem cells for paralysis paper & media coverage

A new paper on stem cells for paralysis from a Mayo Clinic team has sparked a bit of legitimate hope but also some hype in the media.

The publication was in Nature Communications. It is entitled “Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial.” The approach was direct injection of mesenchymal stromal/stem cells or MSCs into the spine in patients with spinal cord injury. Compared to some other studies, these injections occurred relatively long after injury.

Since this was a very small, open-label, non-randomized Phase I trial it has very limited power but even so the media has been all over this. It does have some interesting elements.

stem cells for paralysis
A visual conception of a stem cells for paralysis clinical approach.

Measuring safety while hoping for signs of efficacy

What do we know concretely here?

In this particular stem cells for paralysis trial, there was a solid safety profile. That’s encouraging and safety is the main outcome being measured.

However, when participants get the cells in such a trial, of course, they may experience outcomes that seem like possible indications of efficacy. Clinical researchers are going to watch for that as well.

The team reported that 7 out of the 10 participants have potential signs of improvement in aspects of their paralysis.

Why this stem cells for paralysis study is just a beginning

On face value, that sounds quite hopeful and it could be a real signal. I hope it is.

However, it’s not so simple.

Fortunately, these authors are very upfront about possible limitations of their study. For example, they write of their encouraging data, “However, these results are to be interpreted with caution given the intrinsic limitations of Phase I clinical trials.” They also note that their main readout assay of AIS grading could have issues, “Drawbacks of the AIS grading have also been previously recognized.”

They also emphasize that significant, spontaneous late recovery from spinal cord injury is very rare, only around 5%. The rate of improvement they report is far higher than that, which is encouraging.

They write, “However, the absence of controls prevents ascribing the observed neurological improvement solely to the administration of AD-MSCs. Furthermore, it’s essential to consider that the patients included in the study were treated at a quaternary academic center with a highly specialized multidisciplinary team, which likely provided rehabilitation support that differs from what most spinal cord injury patients typically receive.”

In other words, additional, larger controlled studies will be needed to have a clearer sense if this approach works.

Media coverage of this stem cells for paralysis trial

Despite the limitations, the media have in some cases gotten carried away with this story. Part of what makes it so enticing is that there is a compelling patient story from this trial. For example, here’s a piece from the Independent: Paralysed surfer says stem cell treatment using belly fat helped him to walk again.

This is really something.

Some may ask, “It’s got to be the stem cells, right?” Actually, as The Mayo team said in the paper, we just don’t know yet.

The surfer, Chris Barr, is understandably super excited to have all this function back. The media are excited to cover his story too.

I wish him all the best and I hope this approach leads to other such outcomes. But after being in the stem cell treatment arena for around 18 years, the historical precedents in these kinds of very early clinical cases are not so encouraging. There have been many other such “miracle” outcomes for a single patient in a clinical trial. None of those experimental treatments have worked out for larger groups of patients in the long run after more clinical trials.

Some may remember the ALS patient advocate Ted Harada and his improvement with experimental stem cells for ALS from Neuralstem. Then there was Doug Oliver and his improvement with marrow stem cells for vision loss. There have been other such cases with investigational stem cells too.

More broadly these specific ALS and vision cell therapy approaches just didn’t seem to work out. In case of marrow cells for vision loss, other patients even reported their vision got much worse after getting the cells.

Having both hope and some healthy skepticism

I don’t doubt the improvements for Ted and Doug, but they seem to be exceedingly rare cases.

These unique cases could be explained by many factors that don’t translate into large numbers of people benefiting from the same treatment. For example, individual patients may be somehow far more receptive to a therapy than everyone else.

Why might that be?

It could be genetics or a host of other individual factors. Some other non-patient-intrinsic elements may have come into play too like another therapy being received at the same time by this person for something else that somehow helps or some kind of exceptional medical care.

The point is that there are risks to getting too excited about N=1 kinds of cases. In this particular new stem cells for paralysis trial, it’s more than N=1 but most of the media attention is focused on Chris Barr.

The other issue here is the big unknown of the potential mechanism of benefit for paralysis. While mesenchymal cells or MSCs have anti-inflammatory properties, is that what might be at work here in the spine?

Note that on a brief look at this paper’s methods and other methods they cite, it’s also not 100% clear that these are pure stem cell cultures and not the more usual mix of stem and stromal cells in MSC cultures.

The future

Looking ahead, it’s probably justified to do a larger follow-up trial with controls. Such a stronger trial should clarify whether this is a viable approach.

Sadly, unproven clinics sell various kinds of unproven MSCs for spinal cord injury and other kinds of paralysis. Those MSCs are not prepared and validated in the rigorous ways likely used by The Mayo Clinic and are not delivered with the same care by experts.

If you or a loved one are considering stem cells for paralysis at such a clinic, don’t go that route. There are serious risks including CNS infection. One worry about the over-excited media coverage of this new paper is that clinics will use it for marketing.

5 thoughts on “Perspectives on new stem cells for paralysis paper & media coverage”

  1. “it’s also not 100% clear that these are pure stem cell cultures and not the more usual mix of stem and stromal cells in MSC cultures.”

    Can you elaborate on this?

    “If you or a loved one are considering stem cells for paralysis at such a clinic, don’t go that route.”

    I disagree with you here.

    So Mayo Clinic is currently conducting the phase 2 trial as we speak. Though it doesn’t appear to be double-blinded or placebo-controlled. It has 40 patients though.

    Also it’s too bad Mayo Clinic did not use umbilical cords mesenchymal stem because I think they would have had better results.

  2. It depends on the route of administration. If one delivers MSCs directly into the affected organ- a single injection is good enough. They survive for a long time. In a mouse study, we found these stem cells in the chemoablated testes even after one year. But if given through circulation- maybe 2-3 injections after every six months will be great. MSCs are safe and provide improved paracrine support to the tissue-resident stem cells that can restore tissue functions (regeneration).

    1. There are several problems with this comment. First of all, the testes is a unique environment where stem cells can thrive in some cases. Also, you ablated it to make a niche. And this was in mouse. You can’t make generalizations based on that. You don’t know that MSCs engraft long-term in human spinal cord.

      Also, MSCs are not necessarily universally safe or helpful. It depends on many things like the preparation, the delivery, the health condition, the patient….

  3. A. Rahman Ford, JD, PhD

    In the study, only one dose was given. That’s pretty standard for a trial. But just imagine how much better the outcomes would have been if two or three or more injections were given. WOW.

    Or maybe an injection every six months or once a year. This is how it would work in the real world. And I think this is the cause for all the excitement.

    I for one don’t think hopes can EVER be too high.

    1. More does not always equal ‘better’. Often problems arise from high doses of drugs or even cells. Expecting better outcomes with higher doses is a dangerous assumption. For example, if two acetaminophen tablets help with my headache, twelve of them should be better! That would be a false, and dangerous premise.

      Also the word ‘dose’ is not a quantified number in and of itself, its a generic term here. A dose might be a million cells, or 5-million/kg, or something altogether. One must take great care in these situations to fully understand the science involved.

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