Research Review: A Case Study Examining Stem Cell Transplantation for SCI

DISCLAIMER: I'm not endorsing or condemning anything that was done in this article - rather, I'm trying to review the article presented,and give my perspective (and some critiques) from a scientific standpoint.

On facebook today, I came across a news article about a man who went to Panama for stem cell injections to treat his spinal cord injury.  The full manuscript, "Allogeneic and autogolous stem cell therapy combined with physical rehabilitation: A case report on a chronically injured man with quadriplegia" can be read here.

The article is a retrospective case report - simply put, it is a study with one subject that looks back at an intervention that was already done, and analyzes the results.  I'm actually hoping to do this kind of study with some of my clients at Push to Walk, but that's another blog entry for another time.  The case study reports on a 29 year old man with a C5 ASIA C spinal cord injury, meaning he was partially paralyzed from the neck down.  He had noticeable muscle contractions in almost every muscle of his body, but they were too weak for him to do things like walk, stand, or even sit unsupported or transfer himself on his own.  He went to Panama, had numerous stem cell injections over 5 weeks, came back to the US, and did 6 months of physical therapy and exercising in a gym.  The results he got after those first 6 months back were discussed.

Outcomes: The subject experienced an improvement in strength in 6 of 13 upper body muscle groups, and 8 out of 9 lower body muscle groups.  He also achieved 30 minutes of standing on a tilt table while maintaining blood pressure, and tolerating assisted ambulation in a body-weight support harnessed device.  He did not gain the ability to transfer on his own, but "increased the amount of effort he was able to contribute to these activities."  Perhaps most noticeable was that he had an increase in grip strength - his right hand increased from 5 lbs before the treatment to 22 lbs after the treatment, and his left hand went from 22 lbs before on the left to 36 after.  This increase in grip strength led to him being able to self catheterize, which he was unable to do before the treatment.  The subject was also significantly able to reduce his spasm medication, and moderately reduce his pain medication.

What I like about the rest of the article: the author (a physical therapist who is actually the sister of the subject in this paper) is good at pointing out that "success is not always translated from the laboratory to the clinic" when it comes to stem cell research.  She also mentions that since he got physical therapy and stem cells, it is actually impossible to say whether the improvements he saw were from stem cells alone, physical therapy alone, or a combination.  Were there to be a study with multiple groups - some receiving stem cells, some receiving physical therapy, some receiving both, and some receiving neither, we would be able to say with more certainty what was responsible for the gains.  Additionally, she points out that Manual Muscle Testing, which was the strength tests used to assess the subject's strength in this study, is not sensitive enough to detect small changes in strength that might lead to meaningful functional improvements. (Incidentally, this is one of the things that the new evaluation system we're doing a study on at Push to Walk seeks to resolve.)  The author concludes by saying that further investigation into stem cell treatments combined with physical therapy is warranted, since this one showed improvements in strength and health in somebody 7 years past injury.  Since this was a case study with just one subject (and therefore just one unique spinal cord injury) we can't say that what worked for him will work for everyone, but since it worked for him, we should see if it will work for other people.

What I didn't like about the article:  the author says that "almost all people that sustain a SCI will achieve some recovery of motor function...occurs in the first 3 months after the injury, but the individual can continue to improve up to 18 months after the injury." She goes on to say "...many patients with chronic SCIs do not recover strength so many years post injury with physical therapy alone." She cites one paper to back this fact up, which modern research has pretty much proven to be untrue.  Some research has shown that it can take up to 30 months to reach a stable ASIA score.  One only needs to look at the recent studies published by the NRN to show that people as far as 20 years post injury can experience a return of function with aggressive, high volume therapy.  She also mentions it is hard to say whether the subject in the paper had a truly complete injury or not, even though she shows the results of his pre-stem cell Manual Muscle Tests in the paper, which show us he had some motor function, if only slight, in almost every muscle below his injury. This conclusively shows he was an incomplete injury to begin with - if he were truly neurologically complete, he would have had nothing below the injury!

She also says there is "not a lot of evidence for chronically injured individuals recovering motor and sensory function over 2 years post injury with any type of treatment."  This, once again, has been shown to be completely false, by peer-reviewed scientific research.  The NRN studies have shown this to not be true.  There is also published research on NRN style therapy plus direct electrical stimulation of the spinal cord returning locomotor function, voluntary muscle control, and sensation in chronically injured individuals (4+ years post injury).  She does point out there is a study of a man who went from an ASIA A to ASIA C injury from 5 to 8 years after injury by doing "activity-based recovery", but says this activity based recovery consists primarily of FES cycling (cycling on a stationary exercise bike that directly stimulates the muscles of your legs, so the muscles actually contract).  Activity based recovery is (or really should be) so much more than FES cycling, and generally includes locomotor training, mobility training, balance training, significant amounts of weight bearing, and general strengthening.  The author does say that activity based recovery could be a valuable component to add to the post-treatment phase of stem cell patients, but it seems the author needs a better understanding of what activity based recovery truly is.

My scientific critiques: the subject in this article hadn't done any kind of physical therapy or exercise at all since leaving his outpatient therapy after he was injured.  Therefore, for almost 6 years he did nothing besides some stretching and range of motion exercises, yet the article does not state how frequently.  Therefore, it is very plausible that if he had done his physical therapy and gym exercise (2 days/week of each) without stem cells, he would have seen gains.

As the author said, there is no way to know for sure how much stem cells contributed to his gains now, but if we look closer there is some evidence.  The subject had function in almost every muscle of his body, and hadn't done physical therapy or intensive exercise in 6 years - this means he had lots of strength to gain everywhere in his body.  Additionally, axons in the central nervous system (the wiring that lets muscles communicate with your brain and spinal cord, and vice-versa) grow very slowly - the same speed as human hair at the fastest.  Therefore, it is unlikely that lots of new connections were made in only 6 months after the stem cell treatments.  It seems more likely to me that the gains he made were mostly from physical therapy and exercise, and less from stem cells.  Physical therapy and intensive exercise have been shown to reduce spasticity, increase strength, and in some cases, increase function.

A smarter way to approach this would have been to do physical therapy and exercise first, before ever receiving stem cell treatments, for a number of reasons.  One, stem cells cost tons of money, as do plane tickets and lengthy stays in Latin America, China, or Europe.  You're better off seeing what kind of gains you can make on your own before spending all that $$.  Number two, once you've maximized all your abilities on your own, if you do get stem cells, then you will know how much they really helped.  A lot of "stem cell tourists" get these injections after not having even attempted to regain function on their own for a number of years, then go through physical therapy or aggressive exercise, then see gains.  So how do we really know that stem cells were the catalyst for those gains, and not just the therapy or exercise that someone is engaging in for the first time in years?  Its basic exercise physiology that if you haven't exercised in years, then start exercising, you're going to see improvements.

In Conclusion: The biggest thing I got from this article is that this subject had no adverse health effects from the stem cells.  This is a good thing because I have heard about people who have gotten worse after receiving stem cell treatments.  So if anything, this case study shows us good evidence that someone 6+ years post injury can go through stem cell treatments and physical therapy and exercise with no adverse health effects.  Other than that, not too many conclusions can really be drawn as to the efficacy of stem cells themselves from this case study.  Yes, further research on stem cells is warranted, but they are not the only hope for regeneration after a spinal cord or other central nervous system injury anymore.  I encourage everybody to stay up on their regenerative research and be aware of all the things being investigated that are offering hope to those with paralysis.  And, if you ever do think about getting stem cell treatments, please make sure you've exhausted all your other options first, such as physical therapy or aggressive weight bearing exercise to attempt to make gains.  While stem cells may work, there are almost always other options that could be effective that are most likely cheaper and much closer to home.

Don't search for an answer without regard to validity...

Let the Research Begin!

So the last bullet point in my doesn't-do-the-last-year-of-my-life-justice blog entry talked about the research that I will be doing at Push to Walk. At least as soon as I have the time to begin data collection!  Here is a link to a  press release we did about it.

In a nutshell, for a long time we have needed a better system than what we have been using to assess the strength and progress of our clients.  However, as a small non-profit, we don't have the money for expensive equipment or access to facilities that have them.  So what do we do?  Buy a relatively non-expensive piece of equipment called a muscle testing dynamometer and invent our own way to use it to evaluate our clients.

But how do we know that the system we come up with is any good?  By testing it out.  We will have multiple trainers evaluate multiple clients, and compare the results each trainer got to make sure that no matter who evaluates a client's strength, the same results are obtained.  Using statistics (yay, fun!) we can establish whether or not the new evaluation system is reliable.  That is to say, we will see if the new evaluation system accurately and consistently measures the change (or lack thereof) in strength of our clients at various joints in the body.



It was important to get our study approved by an Institutional Review Board, or IRB.  Why?  The main reason is because doing research on human subjects and attempting to get it published without IRB approval is illegal!  IRBs exist to protect any human research subjects.  Before we could embark on our research, we had to write up a proposal outlining our research, what it entailed, how we would ensure the safety of our subjects, and many other details.  The IRB at William Paterson University agreed to oversee our research, and they approved it!

So in a few weeks, when we have enough trainer staff to test out new system on clients, we'll begin our research on the reliability of the NIMS test.  I have a ton of other research ideas I want to discuss, but in the interest of keeping my blogs short and readable, I'll save those for another entry.

Take three...

Well the "Tips of the Week" failed pretty miserably eh?  Last blog post was almost a year ago.  That is pretty weak.

At the gentle, friendly, constructive encouragement of my younger brother, I have decided to try yet again to maintain a somewhat regular blog.  If the last year is any indication, writing a blog entry every week for the sake of writing a blog every week probably isn't going to happen.  And its better that way, because if I write only when I'm compelled to, I'll write better entries anyway.

So what has happened since my last blog post?  Here is a list, in (attempted) chronological order, of things that have happened, most of which I won't elaborate on enough to show how significant they were:

• I went full-time at Push to Walk, and eventually became the Program Director.  I still LOVE my job and couldn't imagine doing anything better.  I am now living the new American dream (I got a job after college.)
• I got engaged to my girlfriend of almost (at the time) two years, Mary.  I still don't know how I got lucky enough to have her in my life.  Every day with her is a blessing and I'm looking forward to spending my life with her.  You can read more about us at www.sutorfamily.com.
• I drove my new fiance insane with my obsessive following of the throwing events at the Olympics.
• I went to the Working 2 Walk conference in California, the annual conference that promotes advocacy and research for a cure for spinal cord injuries.  I got even more out of it than I did the previous year in Baltimore, made some new friends, and got tons of new information.  It reaffirmed my current passion for being a soldier in the movement to cure spinal cord injuries.
• I designed (with help from others at Push to Walk) a new system to evaluate the strength of our clients, and received approval from the Institutional Review Board (IRB) of William Paterson University to have their help and oversight as I investigate the reliability of our new system.  Hopefully this is the first of many studies that will come out of Push to Walk!

I'll cut myself off there for now.  I want to write a blog about the current research project we have coming up at P2W as well as other things going on at work, but if I write it now I'll just incoherently ramble on forever and nobody will read the whole thing.  So until then, I'm goin' for a walk...