Mesenchymal Stem Cells: An interview with Dr. Jeffrey Cohen

Could you explain the stem cell procedure that you’re testing?  

There are currently eleven medications approved to treat multiple sclerosis and several more around the corner. The available medications are all useful in relapsing MS – an inflammatory phase in the disease – but there is a big need to find treatments for progressive MS. We think this will require different strategies, such as neuroprotective treatment strategies or repair-promoting strategies, which has led to a lot of interest in cell-based therapies.

There are many types of stem cells. The type we are testing are called mesenchymal stem cells. These cells are present in many tissues of the body, and have been studied fairly extensively, which is why we chose to focus our research in this area. In our study, the stem cells were extracted from the patients’ bone marrow, then the cells were grown in the lab to purify them and increase their numbers. They were then frozen and at the time of treatment they were thawed and injected intravenously back into the patients.

Was there a specific reason you chose to look at mesenchymal stem cells?

There has been a lot of research on mesenchymal stem cells in a variety of animal models, a variety of laboratory studies, and also in other conditions, which provides valuable background information. They also have several properties that make them of interest for treating MS. First, they appear to have neuroprotective or tissue-protective properties. They also appear to encourage intrinsic (or natural) repair mechanisms within the tissue. They have some immune-modulating properties – even though that wasn’t our prime motivation, it was an added benefit. Finally, they appear to be able to migrate from the blood into tissues that are inflamed or damaged, which allows for a much more convenient way of administering the cells. We don’t have to inject them directly into the nervous system – we believe that we can introduce them intravenously or via a spinal tap and they will find their own way to the areas of damage.

What are you expecting to learn from this study?

The study we just completed was what’s called a phase I study. It focused on feasibility and safety of the procedure. The results were very encouraging; we didn’t encounter any practical issues or safety concerns, and very few side effects. We also took a preliminary look at benefit – both reported by patients themselves and clinical measures – and a range of advanced imaging and immunologic techniques. Not because we thought we’d get a definitive answer on whether this approach was effective, but rather for preliminary indications of whether the procedure was helpful, how much it might be helpful, how long the benefit might last, and to practice specific assessments in preparation for what we hope will be a larger study that looks more directly at benefit.

You said the study is complete, but could you talk a little bit about who was included in the trial?

This was a relatively small study. We enrolled 24 people with MS. Approximately half had relapsing-remitting MS and half had more severe secondary-progressive MS. We wanted to assess a wide range of people to see first of all if there was benefit in one stage of the disease or another, and more importantly to see if there was any indication of safety concerns in one stage or the other.

One concern we had when we started this study was that there have been experimental treatments that seemed like a good idea for MS but in fact didn’t work and made the disease more active. There are biological properties in these cells that make this a plausible concern. What we were looking for was any indication that these cells made the disease more active after we administered the cells. Thankfully, we didn’t see any evidence of that.

People in the study were enrolled and then underwent a bone marrow extraction. It took four to five weeks for the cells to grow in culture. Over that time we did a variety of assessments of disease status After that we infused the cells back into the participants, and we monitored them for the following six months, looking for evidence of any side effects or complications, and any indication of improvement.

Were there any particular types of MS or people who were excluded from the trial?

Because this was a preliminary safety study, people on certain medications were excluded. We excluded people taking potent immune-suppressing drugs, because we wanted to make sure that if someone had a complication, we knew whether it was due to the cell therapy or the medication. There is also concern that some disease-modifying therapies may interfere with the ability of these cells to migrate or to repair damage. For example, Tysabri, one of the approved medications, works by blocking immune cells migrating into the nervous system and we think it may do the same to these stem cells.

There were also restrictions on other medical conditions and age. It was an intense study in terms of the number of visits, so that restricted it to people who could get to Cleveland to participate. Since we encountered very few safety issues, the hope is that the next study can be more relaxed in terms of the eligibility criteria and the number of visits required.

Do you know when you’ll have final results from the trial?

We are finishing up tabulating the results now. They will be presented at the upcoming joint American and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS) meeting in Boston in September, and several publications are also in preparation. We hope to have the results published this year.

Is there is anything else you’d like to share about the trial?

We were pleased that the study went so smoothly, but it was apparent that there were a lot of issues related to stem cells, includinguncertainties of how best to grow them, where to isolate and administer them, and the optimal dose.These are all issues we are discussing as we plan the next study.

Is there any advice or caution you would offer people as they consider stem cell transplantation, either through a clinical trial or a clinic not associated with a trial.

I share in the excitement and interest in cell-based treatment for MS – it shows a lot of promise. I also appreciate that people are anxious to pursue those therapies now. But it is also very clear to me that there are a lot of unknowns in cell-based therapies. We don’t know which cell type is the most appropriate to use, where to isolate the cells from, how best to grow them in culture. We also don’t yet know the correct dose or best route of administration.

At this point I think it is premature to pursue cell-based therapies outside of a carefully conducted, formal clinical trial. It is premature to pay large sums of money and travel to other countries to get these therapies. I have concerns that what is being done in many clinics around the world isn’t clear, and that we aren’t ready to pursue these therapies outside of clinical trials.

If someone were to consider entering a trial how would they know where to look or what questions to ask to ensure that it is a carefully administered trial?

Clinicaltrials.gov and the National MS Society have a listing of ongoing studies; the International Society for Cellular Therapy is a useful source of information on cell-based therapies.

General questions people should ask are: What is the rationale for this particular cell therapy? What kind of experience do the investigators have? What is the plan to monitor for safety? I think a red flag would be if the plan is to have the cells administered and send you home with no follow up.

Do you anticipate that the next trial you conduct will be conducted solely in Cleveland again?

That is something we are wrestling with. On one hand we’d like to open this up to people that live further away. However, growing the cells is tricky so it’d be very hard to manufacture them at other institutions. We are considering a compromise in which cells are isolated, grown and administered here, but some of the other follow up could be done elsewhere. In which case, it would require one to two trips to Cleveland.

What makes you so excited about research in this area?

It’s an area of big unmet need in MS and other conditions in which there is injury to tissue. And the work that has been done so far has been very promising. I believe cell-based therapies are going to be a big part of medical practice in the future.  The particular cells that we studied are the initial endeavor, but there are a number of other more advanced cell therapies that are being developed. I think there’s a good chance in the future this is going to be how we treat a lot of diseases. 


Jeffrey Cohen, MD, has worked at Cleveland Clinic's Mellen Center for Multiple Sclerosis Treatment and Research since 1994. Dr. Cohen has a large clinical practice devoted primarily to the care of patients with multiple sclerosis and related disorders. In addition, he is Director of the Experimental Therapeutics Program and has been involved in various capacities in a large number of clinical trials developing new therapies for multiple sclerosis. 

** Join the conversation about stem cells and MS here. **

Tags Research      6 Appreciate this
| Reply

The National MS Society

Leave a Comment

Thanks for sharing your thoughts with the MSconnection.org community. Please note comments are moderated.

    13 Comments

  • marshina   Aug 25, 2014 11:35 AM
    Needless to say, this is not a comforting report. I was speaking to several doctors from Stanford and I asked how was it that Jonas Salk was able to discover a vaccine for polio so quickly and now any neurological disorder has only meds that help but not cure? I also wonder where the 50 million dollars raised for ALS will go? Is it our capitalist society that blocks cures from happening? For so many decades now, I thought a cure might be in my lifetime. How naive I was!
  • annsheken  Aug 25, 2014 11:44 AM
    We need the minds of Jeffrey Cohen, James Yarger (endece.com), and other scientists to expedite cures for all kinds of MS.
  • Michael Lesher   Aug 25, 2014 5:47 PM
    This research sounds like another band aid, your not looking for the root cause. There will never be a cure for MS or any other disease, because there is no money to be made in a cure. This was learned a long time ago. If a cure is found then a component or two is removed so the disease is slowed, that why the person will have to take the drug for the rest of there lives and keep paying while the manufacture rakes in the money. I know this will not be seen because the truth can not be known.
  • Allyson Raymond   Aug 26, 2014 7:02 AM
    I think this is exciting news. I just wish they could speed things along...A LOT! My husband has Progressive MS and he'll be in a wheel chair before the stem cell treatments are approved at this rate! We all need to be vocal about this research and our gov't and religious fanatics need to educate themselves! I bet if it were their family member suffering, they would feel totally different about it!!
  • Rebecca jones   Aug 26, 2014 6:34 PM
    I hope u find a cure for ms & all the other cancers out there to relieve them of there issues & get better soon.
  • Garre   Aug 28, 2014 9:41 AM
    I am a religious fanatic that is in support of this type of stem cell research. There are no others that are affected other than the patient. Please keep this procedure in your prayers because without God there is no hope.
  • Emily Brown   Aug 28, 2014 10:08 AM
    marshina,

    Unlike MS, polio has a known cause, a virus. Until we know exactly what causes MS, we can't cure it. Since there are several factors that may (or may not!) cause it, making a vaccine isn't possible right now. Current thinking is that MS is caused by an immune trigger (possibly a virus?), environment, and possibly genetics. All three of these things need to be present for MS to happen, and we're not even sure what they are!

    Any research into ALS will help those with MS, as it is also a neurodegenerative disease (though in MS is it myelin reduction, which leads to axonal degradation). You never know what will help!
  • Tracey   Aug 29, 2014 6:52 PM
    I'm pro choice but that doesn't mean I'm not pro life and have my own spiritual and religious beliefs of my own!! God give's you a choice so as I also see it God is pro choice as well but that really isn't the point at all, what ever happened to separation of Church and State? Why are people so blind that they let elections be won on religious beliefs that are against their own best interest. I'm at the point now where I need repair therapy for my MS and use maintenance meds. Our Government stumbles around stem cell research in the name of God!! What about a family that loses a child to a mis carriage should they not have a say as to where the embryonic fluid goes? Should not their tragedy be someone's hope for survival? Let's put a end to Government's control of us and our human rights to give life at our own beliefs and choice. I'm in now way for abortions but a women has the right to make her own decision. Between abortions and miss carriages there are so many stem cells just thrown away!!! Both are very horrible experiences. But why not use it as a positive to help so many people.
  • Wendel   Aug 30, 2014 9:20 AM
    http://patienttalk.org/killer-t-cells-a-new-way-to-fight-multiple-sclerosis-read-our-interview-with-gary-allen-one-of-the-test-subjects-for-prof-michael-pender-ms-research/
  • Wendel   Aug 30, 2014 9:20 AM
    http://patienttalk.org/killer-t-cells-a-new-way-to-fight-multiple-sclerosis-read-our-interview-with-gary-allen-one-of-the-test-subjects-for-prof-michael-pender-ms-research/
  • LAURIE GARVIN   Aug 31, 2014 10:16 AM
    I would like to be a part of this process please contact me 4405529662
  • Brian Rothermel   Sep 2, 2014 3:00 AM
    I was patient #4 to receive Tovaxin vaccine now renamed Tcelna at Baylor College Med. Houston Tex. in 1998 got !st MBP cloned t-cells 7 million each x 5 per auto-reactive MBP cells cloned in lab, irradiated 98% dead injected 35 million dead MBP attacking cells 35-40 million total. Sub-q injection caused big lump on arm meaning my immune system was fooled into thinking the injected cells were invading immune system, so those cells got killed by my normal defending t-cells. Went from 4 EDSS score to 1 after 3rd inj. at one month intervals. All white active lesions non detectable on next MRI optic neuritis 95% resolved, went to 1 EDSS score. Got 15 vaccines total, last one 1998. I was cured of all white lesions , but 1 dark lesion stayed same already being dark scar tissue. If I got Tcelna before that lesion was scar tissue I would have been considered cured since all other white lesions and scattered-foci never returned after 9th injection, so have faith in scientist Dr's like Jingwu Zhang principle investigator and all who try to obliterate MS. Yes drug companies want to sell drugs, but thank God they were FDA approved and help so many people until a cure is found. I made 44 trips to Texas study duration from Ilinois and wish I could still go, but 18 to 55 is age limits and I'm blessed to have lived to 59 and going strong- diagnosed at 40 years old my neurologist thought I would live only 3 years, that's how relentless my disease was progressing. Cleveland clinic is doing mesenschymel stem cell infusions produced from your own stem cells taken from hip bone marrow and dark lesion scars are remylinating- so keep the faith on a cure, it will happen! Brian Rothermel
  • Steve Johns   Oct 23, 2014 8:05 PM
    Drug regulation reform.

    I note Jeffery Cohen has excluded Primary Progressive MS from his trial.

    Our system for treatment evaluation badly needs reassessment and reform. The system originated because of a need to protect people from snake oil salesmen but has been debased into a system for protecting vested monetary interests at the expense of the people it should be protecting.
    I have PPMS and have been involved in a phase 3 trial of Fingolimod for the last 3 years (now extended again to 4 years). As you know it was approved for other types of MS in about 2008 but, as PPMS had been kept out of the previous trials, not for Primary Progressive. This has of course only removed 10% of the ‘market’ (read people who need it) and has allowed Novartis to wait a few years then run these trials and then claim a ‘new application’ and so extend their patent by about 8 years allowing them to continue to charge $3000 for 28 day’s supply.
    This highlights 2 issues. Firstly the drug has been shown to slow the progression of the disease. There would not be a phase 3 trial at all if no effect had been observed. In PPMS the average progression from diagnosis to death is about 17 years and there are no other treatments for the progression of this disease so with holding this drug from this group for 8 years is a significant sentence for these people and a serious abuse of human rights.
    Secondly the use/abuse of the system to extend the life of their patent and so allow the company to sell the drug to 90% of their market for 8 years and then start the clock again on the patent for 100% of the market at a price that is determined by how much can be screwed out of government subsidies (they couldn’t sell it for this amount otherwise) is a serious rort and amounts to fraudulently obtaining tax payers money.

    This is technically not criminal because it is not illegal but it is certainly not ethical or morally justifiable. It has denied access to this drug for the people (yes PEOPLE, patients are people) who could have benefitted from this drug for 8 years, during which time many have suffered terribly, and all in the name of company profits and, possibly, jobs for people conducting the new round of unnecessary trials. This corruption, and it definitely is corruption, is the main reason why reform of the system is so badly needed.
    Another part of the system that needs reform is the trial process itself. The double blinded, placebo controlled trial is the gold standard for identifying and quantifying effects but is not necessary in many instances for approving drugs and only serves to make trials far more expensive than necessary. Such a trial is unarguably the most accurate but what is needed is the most appropriate method of assessment. This will be the type of trial that gives the most relevant information to what the trial is assessing. If a drug has been shown to be safe and to have an effect in phase 1 and 2 trials and to, for example, slow the progression of a disease by approximately 70%, then a phase 3 trial should be unnecessary or could be simplified, speeded up and made more effective. The placebo control group could be eliminated entirely because there will always be a placebo effect in some people when the drug is available on prescription and the control is the entire medical history of the disease to date. This is not as close to an exact comparison as with a placebo control group but even such a control group is not an exact comparison. In this instance though this would be irrelevant because the placebo effect will not be 20% and the difference between ‘approximately 70%’ and ’67.32 percent makes no difference to anything. You could treble the size of the trial and perhaps calculate the results out to 67,3897348% and this would be far more accurate but gives no additional useful information.
    In this instance then if all participants in the trial were given the active drug, as opposed to half receiving a placebo, then the size of the trial is doubled and this in itself tends to even out the effects of any aberrant individual reaction.
    It is also far more ethical to give all participants the active drug than to deceive half the participants to observe their decline and suffering to be able to get a more accurate assessment of the last decimal place for the percentage effect. In fact when you know that the effectiveness is, say, 70% then the use of a placebo this way is immoral.