Neural Stem cells to the Rescue?. Phase I trial results

VK Harris et al. Phase I Trial of Intrathecal Mesenchymal Stem Cell-derived Neural Progenitors in Progressive Multiple Sclerosis
EBiomedicine DOI:


Multiple sclerosis is one of the leading causes of disability in young adults. Our study is the first evidence suggesting that a cell-based therapeutic approach is capable of reversing disability in multiple sclerosis. Results of our study add to existing evidence demonstrating the safety and tolerability of intrathecal administration of autologous mesenchymal stem cell-derived neural progenitors. The study was associated with repeated administrations of cells freshly harvested from culture, as opposed to cryopreserved cells thawed at the bedside, which may have contributed to the observed efficacy of the treatment. The continued development of this therapeutic approach will likely have implications for treating other neurological diseases.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system and is one of the leading causes of disability in young adults. Cell therapy is emerging as a therapeutic strategy to promote repair and regeneration in patients with disability associated with progressive MS.
We conducted a phase I open-label clinical trial investigating the safety and tolerability of autologous bone marrow mesenchymal stem cell-derived neural progenitor (MSC-NP) treatment in 20 patients with progressive MS. MSC-NPs were administered intrathecally (IT) in three separate doses of up to 1 × 107 cells per dose, spaced three months apart. The primary endpoint was to assess safety and tolerability of the treatment. Expanded disability status scale (EDSS), timed 25-foot walk (T25FW), muscle strength, and urodynamic testing were used to evaluate treatment response. This trial is registered with, number NCT01933802.
IT MSC-NP treatment was safe and well tolerated. The 20 enrolled subjects completed all 60 planned treatments without serious adverse effects. Minor adverse events included transient fever and mild headaches usually resolving in <24 h. Post-treatment disability score analysis demonstrated improved median EDSS suggesting possible efficacy. Positive trends were more frequently observed in the subset of SPMS patients and in ambulatory subjects (EDSS ≤ 6.5). In addition, 70% and 50% of the subjects demonstrated improved muscle strength and bladder function, respectively, following IT MSC-NP treatment.
The possible reversal of disability that was observed in a subset of patients warrants a larger phase II placebo-controlled study to establish efficacy of IT MSC-NP treatment in patients with MS.
Here are exerts from the paper which is open acess
“The clinical feasibility of IT MSC-NP treatment in MS was initially investigated in six patients with advanced MS treated with two to five injections of escalating doses of autologous MSC-NPs. PwMS were followed an average of 7.4 years after initial injection. There were no serious adverse events or safety concerns noted, and the treatments were well-tolerated. Four of the six patients showed a measurable clinical improvement following MSC-NP treatment”. 
In this current study “eligible patients had clinically definite SPMS or PPMS with significant disability (EDSS ≥ 3.0) that was not acquired within the 12 months prior to enrollment. The inclusion of patients with a relatively stable disease state was designed to allow better discernment between natural disease progression and treatment-related events. To minimize additional variables, patients who were already receiving disease-modifying therapies (DMT) upon entering the study continued as a concomitant treatment through the course of the study”. 
“There were no serious adverse events or hospitalizations associated with IT MSC-NP treatment” 
“The safety data was further supported by a lack of any change in brain MRI scans during the study. Specifically, no new T2 lesions or changes in disease burden were observed”. 
“The study design was not blinded, and there were no placebo controls”. 
Therefore, be warned the power of the placebo should not be under-estimated. The placebo effect where you get better after taking nothing can be immense and has sent many good ideas to their graves.
The primary post-treatment clinical assessments were conducted at three and six months following the third treatment and compared to baseline (pre-treatment) in order to determine trends in efficacy. Of the 20 study subjects, 15 (or 75%) demonstrated neurological improvement associated with IT MSC-NP treatment. 
Improvements were documented in the following areas: EDSS, MRC muscle strength scale, timed 25-ft walk (T25FW), and/or bladder function.Of the remaining subjects, two showed disease worsening despite the treatment, and three subjects showed no change.
The predefined endpoint was adverse effects but secondary endpoints were evidence of efficacy allowing the centre to pick and choose and so data hack to spin the best story. 

So as you can see 4 people showed qute a bit of improvement and there were reports of improvement for other outcomes notably the lower limbs and bladder rather than upper limbs and cognition.

So first things first you can see it is not a miracle cure and therefore we need to view these results positively, but also objectively. 

The myth being spun is that stem cells will turn back the clock and for most people here, this is not the case, so we need to understand the reality of these studies. It is a start

This study injected live growing cells and so they are producing a group of “potential goodies” that may be growth factors.

About the author



  • However, few months earlier you were a little harsh on the stem cell therapies (the mesenchymal ones), so maybe Tisch is baking you a humble pie 😉

    Seriously, Tisch has showed good science ethics and we are crossing fingers for their results. However, I am afraid that even if it works it will be an unaffordable treatment.

    • It's important to note that the study is short-term so it is important that long-term follow up is done to determine whether benefit in those 4 pwms showing an improvement is sustained or a transient effect.

    • "I am afraid that even if it works it will be an unafordable treatment."

      Not in the U.S..lowly BetaSeron costs govt. $7,000 a month or is it $8,000..I forget..ahh what's the difference.
      What I read here about budgets and funding in u.k. is sometimes shocking to did the royal family loot the country.

      Sad to see this study like most others shows little/no improvement above EDSS 6.5..:(

    • True, because it is a therapy that is difficult to repeat. However, if the results wont last long, that would not mean that the treatment is unsuccessful, that would mean it is just a not viable (economically and practically) solution.

    • I believe these are neural stem cells made from mesenchymal stem cells rather than mesenchymal cells.

      They can bake a humble pie but I would prefer a Shepherds pie if they want me to eat it, but not sure I need to more humble than usual:-)

      Sad to see little or no improvement above EDSS 6.5. As we have said many times those with reserve capacity have advantages and the best way to repair is to protect against loss in the first place.

      How long do the cells last, often in animals if is a few days. There are many unanswered questions. some may be answered with further work, we'll report it as it arrives.

    • "Sad to see little or no improvement above EDSS 6.5"
      It's worse than that..the graph clearly shows a
      wall at EDSS 6.5 w/ no improvement while EDSS 6.0 gets improvements.
      Just .5 makes such a huge difference.

      Suggests that beyond EDSS 6.5 one needs axon sprouting in the CNS followed by remyelination therapy to see any improvements at all.

      Do you know/heard anything about axon sprouting research..?

    • Yes, “the best way to repair is to protect against loss in the first place”. unfortunately many patients are progressing even while on dmds. After age 50 the available drugs are not effective according to an earlier post. What to do as we watch ourselves lose neural reserve and function? Neuroprotectants would be welcome until then hope turns to other means.

    • "Do I know…axon sprouting….Yes I have"

      As I understand it axon sprouting naturally occurs in the periphery for repair but can't happen in CNS..?

    • We have evolved mechanisms to block sprouting in the CNS and this is for a reason. We have anti-LINGO-1 as a remyelinating drug but remember it is a molecule that blocks the brake on sprouting.

      Repair can be connectivity, which is synapse formation. Last year we saw the guy with a stab wound in the spine walk again. This is due to connectivity…sprouting or synapses.

  • I'm a patient at the clinic associated with the Tisch research center. They share a facility.

    This study was finished up some time ago; phase 2 is scheduled to begin sometime later this spring or early summer.

    In phase 2, patients will be given either neural progenitor cells or placebo. Intrathecal injections will be given every two months (six treatments a year) for the first year. Those patients on placebo will be given stem cells during the second year. Patients given stem cells during the first year will receive more stem cells during the second year, but with less frequency.

    It's important for patients to keep in mind that any regenerative stem cell therapies will likely require repeated infusion/injections in order to sustain or advance benefit. The stem cells themselves do nothing to address the underlying disease process, therefore, without repeated applications any repairs affected will be subject to the disease process. Thus the need for repeated treatments. Patients spending tens of thousands of dollars at for-profit extensive clinics really need to understand this, as one treatment, even if successful, will not offer sustained benefit. Better have a very large bank account if you decide to go that route, and the therapies being explored at the Tisch center are far more sophisticated than those being offered at most for-profit clinics.

    The Tisch center is currently in the process of building out the largest stem cell laboratories devoted to MS research in the world. They should be able to handle the processing of stem cells for 50 patients sometime within the next few months.

    Tisch is taking bone marrow derived mesenchymal stem cells and transforming them into neural progenitors using a proprietary process. In addition to stem cell research, they are hard at work identifying markers for disease activity, inflammation, oxidative stress, and other measures – all primarily using cerebral spinal fluid. In addition, they are actively seeking innovative treatment therapies and searching for the root cause of the disease.

    The lead researcher (and my personal neurologist), Dr. Saud Sadiq, is absolutely obsessed with putting an end to ms. He works at least six days a week (he has a bedroom with full bathroom facilities attached to his office), and can more often than not be found at the facility, at almost any hour of the day. He's not associated with any academic or hospital institution, and thus is able to pursue any avenue of research he chooses. He does not allow pharmaceutical representatives to even enter his clinic, and forbids any of his staff from receiving monies from pharmaceutical companies.

    The Tisch research foundation itself is a certified nonprofit organization.

    On a personal note, Dr. Sadiq and I have an almost familial relationship. I've been seeing him for almost 14 years, and my respect and affection for him know no bounds. This even though he's not been able to put much of a dent in the progression of my rather atypical case of PPMS – so atypical that we've agreed that in my case the initials stand for The Peculiar Paralysis of Marc Stecker.

    I'm also familiar with many of Dr. Sadiq's staff researchers, who share his commitment to put themselves out of business. Let's hope they succeed in that quest sooner rather than later…

    • thank you for the informative and personal summary. as a pwms i find this site to be so interesting to hear everyone's stories; and hearing the drive of the doctor you quite clearly admire, along with the drive of the doctors at Barts (which is my hospital) to end MS. It makes me feel really grateful.

      keep up the good fight all!

    • I'm also Dr. Sadiq's patient (I see two different neurologists regularly), and can also report how caring and dedicated he is. He's frustrated by the big pharma chokehold on research and he really cares about finding a cure. In his clinical work, he offers the same advice about brain health that this blog does, and he's very focused on the whole person.

    • Thanks for that. Maybe Dr Sadiq might like to contribute a post for the blog? I'm sure that would be greatly appreciated.

    • I conducted an extensive interview with Dr. Sadiq this past weekend about the results of this phase 1 trial, as well as the upcoming FDA approved phase 2 trial. I will be publishing this interview in two parts on my blog, Wheelchair Kamikaze (

      Lots of interesting insights regarding results, possible mechanisms of action, and a host of other topics associated with these trials.

      I would be happy to share this interview on this blog if the powers that be desire. Of course, I'll have to publish on my blog first, and I plan on publishing in two parts. Part one should be published either tonight or tomorrow night.

      As far as Dr. Sadiq working with the Israelis, so far their approaches are similar but different. To my knowledge, the Israeli stem cell project is using raw mesenchymal stem cells, while Dr. Sadiq is transforming those cells into neural progenitors. There is a lot of information sharing among the community experimenting with stem cells for MS, both at conferences and individual to individual.

      Please let me know if Barts and London would like access to my interviews for use on this blog. I believe some of the good folks there already have my contact info.

  • Good Morning,
    I think that this work is very close to the study taht is been conducted in Israel by Dr. Karussis in Hadassah.
    Am I right?

    I would like to ask to The Wheelchair Kamikaze what does Dr. Sadiq thinks about work together with Dr. Karussis. I think that would be a good think to merge they knowledg.


    • There is a difference. From what I understand Dr Karussis is injecting undifferentiated mesenchymal stem cells rather than neuronal progenitors derived from mesenchymal cells used in the Tisch study. which may explain why the results would seem to be better in the Tisch study.

  • Interesting that improvements were in lower limbs. Could the treatment be helping spinal lesions? My lesion load was all in spine causing foot drop. Interestingly it has all remylinated according to my last 2 MRIs. Totally normal. Am told that as my foot drop is still there the underlying nerves are damaged. Would love this treatment to see if it helped.

  • I am trying to digest this data. Two very disabled patients showed worsening after the stem cells, but every patient had to have a stable EDSS before being included. Did the stem cells cause progression? Were they also older? I have been following Richard Cohen's blog. He says he had a very serious form of Psoriasis (possibly life threatening) develop on the heels of the first stem cell infusion as well as many DMT interventions after the stem cells. How can we tease out who would benefit and for whom this could be useless or risky?

By MouseDoctor



Recent Posts

Recent Comments