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Thread: Just For the Record...

  1. #1
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    Just For the Record...

    Embryonic Stem Cell Research: A Wolf in Sheep's Clothing Regarding Cures?

    I am a paraplegic due to having suffered a spinal cord injury in 1997. My sole hope for regaining the use of my body below my shoulders is through the efforts of medical research. Until recently, I have been strongly in favor of allowing embryonic stem cell (ESC) research to be federally funded. My reason for supporting this position was because I believed the highly publicized claims that ESCs represent mankind's best and most immediate hope to cure a handful of catastrophic, life-threatening diseases or conditions, including my own. My stance in this matter was not affected by ethical issues when I wrote to President Bush and his advisers in favor of ESC funding; nor do the ethics of destroying human embryos for medical research, which are already doomed for certain destruction, affect my position now. My opinions regarding the federal funding of ESC Research have always been based on what I perceive to be the best interests of curative research, and hence, in the best interests of the many millions that suffer the conditions that ESCs might someday address. My priorities haven't changed. I have simply come to believe that the banning of federally funding ESC Research might also serve the cause of hope. In fact, it may serve it better.

    My reasons for having this change of heart are several. In the first place, embryonic stem cell research is still in a very early "basic research" stage. Formidable safety issues and technical questions must be resolved regarding ESCs before they can be used for medical purposes. These issues include the retarding over proliferation, suppressing tissue rejection due to the body's immune-response, guiding stem cell differentiation and maturation into adult tissues, and avoiding the potential for ESCs to form aggressive and lethal tumors (teratocarcinomas). To an apparently much smaller degree (and not at all concerning rejection) these issues are also involved in adult stem cell usage (also called "autologous" stem cells). However, adult stem cells have already been used to successfully treat human diseases, albeit in very small pilot studies (Heart Disease and Parkinson's). Whereas ESCs have yet to be successfully used in humans. For example, Drs. M. Levesque and T. Neuman (1) of Cedars Sinai Hospital in California treated a long-term Parkinson's patient with autologous stem cells (2). Within months of treatment the Parkinson's symptoms completely disappeared with apparently no undesirable side effects or return of Parkinson's symptoms after more than two years having elapsed since treatment. On the other hand, another Parkinson's clinical trial, in which dopamine-producing neurons were grown from ESC sources and implanted in the patient's brains, resulted in disastrous consequences for a few of the patients (3). They developed continuous and uncontrollable spasms or convulsions. It seems that their brains are now over producing dopamine rather than under producing it, as is common of Parkinson's Disease. The reason for this is unclear. However, as no foolproof method of marking stem cells has yet been invented, one possible explanation for the negative impact this treatment has led to in these patients is that ESCs were inadvertently implanted in their brains (leading to the development of more dopamine-producing neurons than intended, per the above reference to "over proliferation"). Either way, adult stem cells have already been used to very successfully treat the same condition that ESC usage has proven able to only slightly improve, or in some cases has undeniably worsened.

    Of course, these issues are what we have basic research for in the first place. They are also part of the reason we have the National Institute of Health (NIH). It is very probable that many of the potential cures for various conditions either at or nearing the clinical stage were initially developed with NIH support. For this reason alone, one would think I would support the federal funding of ESC Research. However, I expect that most of those who look to stem cells to cure their conditions (like me) are not interested in basic research, they're interested in curative results. Medical research intended to lead to a cure may be ready for human testing or rapidly approaching that point. This is what I call "curative" research. "Basic" research, on the other hand, is usually many years away from reaching the curative stage. Basic research may involve spending several years to tackle a single side-issue of a research avenue (such as the obstacles to ESC human usage listed above) without ever addressing the avenue's regenerative or curative aspects. Also, some research is not intended to lead to a cure, such as care or rehabilitative research. In the case of embryonic stem cell research, even its staunchest supporters in Medical Science admit it may be as much as ten years before ESCs can be used in humans to cure anything, and maybe more. This outlook is especially sobering when one considers it reflects the expectations of leading pro-ESC scientists if embryonic stem cell research succeeds in gaining the unrestricted financial support of the NIH. Nevertheless, I would still advocate the federal funding of ESC Research except for the fact that its unrestricted NIH support has the very real potential to seriously hamper or even lead to the abandonment of existing curative research and Adult Stem Cell Research, which is already further developed than ESCs for certain conditions. I base the previous contention on...

    1. the obvious interest the NIH has shown over the past several years in supporting human embryonic research,
    2. on the past behavior of the NIH (and of its leading scientific allies in academic research) regarding research avenues the NIH goes out of its way to sponsor,
    3. on the negative impact its unbalanced support for unproven research has had on other, more promising lines of research...research at both basic and curative stages.

    For over twelve years the NIH once sponsored a nationwide clinical trial that addressed acute spinal cord injury. This study, called NASCIS (National Acute Spinal Cord Injury and Stroke), eventually involved sixteen major trauma centers and led to the acceptance of Methyprednisolone (MP) as the standard acute SCI treatment by the medical community. MP is a steroid that supposedly is neuroprotective, possibly saving spinal cord tissues from secondary injury caused by inflammation, oxidation, and free radical damage. However, the scientist that was eventually recognized as the guiding force behind NASCIS, Dr. Wise Young, Ph.D., claims that prompt MP usage may only results in twenty percent less functional loss (4). Such an improvement is certainly better than no improvement at all. However, after having several years and many thousands of cases with which to clearly assess MP's clinical value, many clinicians and researchers now claim that not only does MP do no good at all, but that it may also harm the patient (5,6,7,8,9). By itself, this issue would have had no bearing on my ESC stance, because in research not all projects are guaranteed to dramatically succeed (although to be honest, I find it disturbing that the NIH thought it worthwhile to tie up its acute SCI clinical resources for over twelve years to achieve such limited results, the degree of which had to be apparent within the first few years of the study). And if the NIH had no other acute SCI options in the mid-eighties they could certainly have been excused for backing MP so wholeheartedly. But such was not the case. Dr. Wise Young, who on the strength of his involvement with NASCIS rose from a junior researcher at New York University to the Directorship of Rutgers University's Neuroscience Center, wrote to the FDA on September 15th, 1985:

    "Some information which might be obfuscated by the volume of the data is summarized in table 10 on page 20 of the report. The eventual percentage of cats receiving PEMF at 4 hours after injury that recovered walking at 4 months after spinal cord injury is 78% (7/9), compared with 0% (0/10) of the sham treated controls. No pharmacological treatment that we have tested to date, including naxolone and methylprednisolone (both of which are in a double blind randomized clinical trial in 12 spinal centers around the country), has exhibited this degree of effectiveness in similar animal studies."

    This letter referred to an acute SCI research project that Dr. Young had been developing for seven years. Along with the manuscript submitted with this letter, he was working at that time on two additional manuscripts to publish the details of this work. Yet, within a few months of sending this letter he completely abandoned this line of research in favor of MP, the very substance he admitted to the FDA was inferior to the abandoned avenue.

    It is true that this example (acute spinal cord injury) only deals with a single aspect of the many medical concerns that face the NIH. It is also obviously an issue in which I had a very personal stake, for no one knows how many of the 450,000 Americans currently paralyzed by spinal cord injury may be walking today had the NIH been willing to retrench their acute SCI program in the eighties in favor of more promising research. To put my concerns in a broader perspective, in the nineties the NIH supported medical research having genetic implications. Their support for this line of research was nowhere near as determined as it presently is for embryonic stem cell research. (The NIH has been seeking approval to fund human embryonic research for at least seven years.) However, the focus at the NIH on research having genetic implications resulted in the words "gene" or "genetic" being recognized in academic research as magic passwords to gain NIH funding of research projects. If ESC Research is approved for federal funding, it stands to have an even more widespread and lasting affect on the direction academic medical research takes in the coming years (and possibly decades), as many researchers are only able to study what the NIH is willing to back. Therefore, when I came to understand both the degree to which the NIH supports ESC research and the number of obstacles that stand in the way of ESCs moving from basic research to full-blown cures, I paused to place this issue in context with their enthusiastic support of specific research avenues in the past. And in doing so I came to the conclusion that the American public cannot afford to support any large-scale program the NIH wholeheartedly backs, for I believe the health the NIH is anxious to protect in this ESC issue is not the health of the American People, but rather the long-term health of American Basic Research.

    James Kelly
    August 8th, 2001

    1. K. Palm, T. Salin-Nordstrom, M.F. Levesque, T. Neuman, Fetal and adult human CNS (Central Nervous System) stem cells have similar molecular characteristics and develemental potent, Molecular Brain Reseach; 78, 192-195 May 2000
    2. T. Neuman, M. Levesque, Human Brain Transplantation Protocol Approved To Reverse Nerve And Brain Damage
    http://www.sciencedaily.com/releases...1031181308.htm
    3. C. Freed et al., Transplantation of Embryonic Dopamine Neurons for Severe Parkinson's Disease NEJM v.344 710-719 March 8th, 2001
    4. Bracken MB; Shepard MJ; Holford TR; Leo-Summers L; Aldrich EF; Fazl M; Fehlings M; Herr DL; Hitchon PW; Marshall LF; Nockels RP; Pascale V; Perot PL Jr; Piepmeier J; Sonntag VK; Wagner F; Wilberger JE; Winn HR; Young W; Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial, JAMA 1997 May 28;277(20):1597-604
    5. Coleman WP; Benzel D; Cahill DW; Ducker T; Geisler F; Green B; Gropper MR; Goffin J; Madsen PW; Maiman DJ; Ondra SL; Rosner M; Sasso RC; Trost GR; Zeidman S. WPCMath, A critical appraisal of the reporting of the National Acute Spinal Cord Injury Studies (II and III) of methylprednisolone in acute spinal cord injury, J Spinal Disord 2000 Jun;13(3):185-99
    6. Hurlbert RJ. Methylprednisolone for acute spinal cord injury: an inappropriate standard of care, J Neurosurg 2000 Jul;93(1 Suppl):1-7
    7. George ER; Scholten DJ; Buechler CM; Jordan-Tibbs J; Mattice C; Albrecht RM; Failure of methylprednisolone to improve the outcome of spinal cord injuries. Am Surg 1995 Aug;61(8):659-63; discussion 663-4, Department of Surgery, Butterworth Hospital, Grand Rapids, Michigan, USA.
    8. De Maria EJ; Reichman W; Kenney PR; Armitage JM; Gann DS; Septic complications of corticosteroid administration after central nervous system trauma. Ann Surg 1985 Aug;202(2):248-52
    9. Qian T; Campagnolo D; Kirshblum; High-dose methylprednisolone may do more harm for spinal cord injury. Med Hypotheses 2000 Nov;55(5):452-3 Department of Physical Medicine & Rehabilitation, New Jersey Medical School, Newark, New Jersey, USA.
    10. Nesathurai S; Steroids and spinal cord injury: revisiting the NASCIS 2 and NASCIS 3 trials. J Trauma 1998 Dec;45(6):1088-93, Boston University School of Medicine and New England Regional Spinal Cord Center

    (excerpt from reference "10")

    "The National Acute Spinal Cord Injury Study (NASCIS) 2 and 3 trials are often cited as evidence that high-dose methylprednisolone is an efficacious intervention in the management of acute spinal cord injury. Neither of these studies convincingly demonstrate the benefit of steroids. There are concerns about the statistical analysis, randomization, and clinical end points. Even if the putative gains are statistically valid, the clinical benefits are questionable. Furthermore, the benefits of this intervention may not warrant the possible risks."

    note: For the reasons stated throughout this post, the final line of the above quote states my ESC stance in a nutshell. What I would have liked to have seen President Bush do optimally was...

    1. restrict ESC usage to stem cell lines proven to originate from embryonic sources irrefutably doomed to destruction as part of the in-vitro fetilization process.

    2. restict the funds the NIH would be permitted to devote to ESC Research such that existing curative research and adult stem cell research would not be compromised.

    3. Safeguard both the above points by the formation of a presidential oversight committee staffed by leading "pro-life" advocates and stem cell experts.

    [This message was edited by James Kelly on August 09, 2001 at 10:16 PM.]

  2. #2
    Super Moderator Sue Pendleton's Avatar
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    Who was this written and sent to, Jim? You might also want to note that MP was, to my knowledge, neer expected to be used on penetrating wounds to the cord because of the chance of infection. And where did the place in Michigan get controls in 1995 that would consent to not being given MP?

    Today, MP is also used to help control flares of MS and to, when diagnosed early enough, stop transverse myelitis from causing permenant damage to the myelin sheathing of the cord.

    As discussed before, steroids at the doses needed to effect the outcome of SCI lesions are not benign substances. They do carry long term risks to bones and connective tissue as well as short term problems by suppresing the immune system. But 20% is a significant amount of function in the fingers of a C6 complete. And an even more significant benefit for those C3 and C4 who are able to be weaned from ventilators.

    And while I do see your point about NIH funding things particuar patient groups are not really requesting, there is the magical pipeline that all breakthroughs must go through before companies or the NIH takes something to human trials. So while I agree that stem cells may not help you and I walk in a year or two they may totally reverse paralysis in 15 years to people newly injured then. In the meantime we need to keep the NIH's noses to the cure grindstone and that means chronics and neuroprotection for the acutes.

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    Hi Sue:< ) How have you been feeling? It's been awhile! But knowing you, whatever you've been up to it's been something good for the rest of us!

    To answer your points as they were raised...

    1. A gentleman involved in the stem cell debate asked me to write a clear explanation of why I changed sides on this issue. To tell the truth, I never really changed sides. I just came to decide that if this came down to an all or nothing decision by Bush, that I would feel better with "nothing." What I REALLY would have hoped to have seen happen is tacked on to the very end of my original post.

    2. Regarding Mp. I'm not going to ague the point anymore. MP may certainly be useful in some cases, but the vast majority of comression SCI's are not among them. IF the cases were diagnosed and treated within minutes of injury (such as Adam Taliaferro of Penn State) then it might be another ballgame...but their not. Therefore, the above references reflect my opinion of MP.

    3. Regarding stem cell research, the ONLY thing I'm concerned about is that ANY single research avenue, however promising, is not allowed to completely eclipse the rest of regenerative research...or at least not until it can be shown without a shadow of a doubt that the avenue in question will lead to cures that are more effective and will come to the market quicker than those they stand to replace. I realize that without large-scale federal support this may be impossible to prove regarding ESCs. However, if you feel comfortable backing the NIH in its efforts to redirect the course of academic research in the hopes that cures may result in 15 years, at the possible cost of impairing the devlopment of cures between now and them, then that's your business.

    James Kelly

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    Senior Member Scorpion's Avatar
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    <<the ONLY thing I'm concerned about is that ANY single research avenue, however promising, is not allowed to completely eclipse the rest of regenerative research...>>

    Agreed. Like the old saying goes, don't put all your eggs in one basket.

    RE: MP - I was administered MP 'on scene' by the EMTs. I had been rescued from a surfing accident, and it was correctly assumed that my neck was broken. This was in Daytona Beach, Florida where Halifax Medical Center is very capable of handling trauma, getting their experience from accidents at Daytona Speedway. Anyway, I fractured C-5, compressing the cord and the body of the vertabra, or what was left, was displaced toward the posterier. I believe MP is one of the reasons I regained so much sensation, albeit a little numb below the chest, and perhaps the wrist extension which clasifies be as a C-6 quad or ASIA B (crap, I'll have to double check that ASIA scale later). This was in 1990 when MP wasn't widely accepted as beneficial.

    ~Rus

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    Rus:

    I'm sorry to learn of your accident. But then, when you get right down to it, most of us have a sad reason for being here, whether it has touches us directly, or someone we deeply care about. I guess what I mean to say is I'm sorry you didn't get more back. From what I've read (and from the recovery of the Penn State football player) I thought MP could do alot better that 20%, which as I've admitted is worth a lot more than nothing. But as you and a lot of us can attest to, a better treatment would have been greatly appreciated. I wonder if the tossing of the waves after your injury resulted in more severe damage than the football player suffered, as they stabilized him immediately upon his head-on collision with the fullback's knee? Either way, if we keep pushing research maybe we'll eventually push ourselves right out of these chairs.

    Good luck and take care!!!

    James Kelly

  6. #6
    I was in rehab with Penn State football player Adam Taliaferro. His therapy sessions, mainly PT, were twice as long as anyone elses. Adam worked very hard on his rehabilitation, and had optimum care. He also had weight supported treadmill therapy and was walking with crutches only two and a half months after his injury. He had the benefit of immediate, professional care at the scene. Isn't it also probable that his spinal cord suffered minimal damage?

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    Rusty:

    I'm sure you're right. I understand they gave him the MP before he left the stadium. Also, I bet they had his neck stabilized within minutes of the injury. I'm curious, though, why was Adam's PT more intense than everyone else's? Also, didn't everyone have supported treadmill therapy?

    James Kelly

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    Senior Member Scorpion's Avatar
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    <<I wonder if the tossing of the waves after your injury resulted in more severe damage than the football player suffered, as they stabilized him immediately upon his head-on collision with the fullback's knee? >>

    Oh, I'm sure it did, and I'm sure there was already more damage to the anterior cord than posterior where sensation is. But I was commenting on what I thought MP helped me with, not trying to tell my sad story. My story is a cake-walk compared to many others.

    ~Rus

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    Super Moderator Sue Pendleton's Avatar
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    Just to clarify:

    "However, if you feel comfortable backing the NIH in its efforts to redirect the course of academic research in the hopes that cures may result in 15 years, at the possible cost of impairing the devlopment of cures between now and them, then that's your business."

    I don't see this as an either or situation, Jim. I see ESC therapy as being somewhere down the pipeline. Trust me, I'm not waiting for perfection for 15 years! Not sitting on my butt anyway. NIH has historicaly been heavy on grants to basic research and I write them too about moving more SCI therapies to trial faster because this is a life shortening condition. So right now I look at M-1, L-1, the several multiple type therapies in Russia and Taiwan and, personally, wondering about the ability to get a hospital IRB to ok an autogolous OEG transplant.

    But I do want people who are injured in 2016 to walk out of the hospital using their own steam after 2 weeks or so. So yes, I support almost all research that will alleviate the miseries of SCI as fast as possible. And for me, that means maybe not funding so many head shrinker studies. Take a Prozac until the cure comes if need be but quit asking me why SCI is depressing.....it just is!

  10. #10
    James,
    My only guess to why Adam had such intense therapy would be that his progress was so rapid, and he was willing to give the extra effort for recovery. I'm not sure why not everyone gets the treadmill therapy, again guessing, they want to see some voluntary leg movement, and since it requires several therapists, insurance might be an issue.

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