Christopher Reeve: An Effective Champion for an Ineffective Cause?

[Wise Young]

Spinal cord injury has become a casualty of the senseless war over stem cell research, waged by people who are either ignorant of the research or, worse, deliberately misleading the American public. These articles invariably say that there is no evidence that embryonic stem cells are effective for treating spinal cord injury, claiming that there is no clinical trial or animal evidence showing that they are effective. They claim that advocates of embryonic stem cell ignore or do not support adult stem cell research. Worse, they claim that "adult stem cells" are already curing diseases such as spinal cord injury and Parkinson's disease, often claiming that nasal mucosal transplants represent adult stem cell therapies. They often suggest that advocates of embryonic stem cell research have some kind of financial stake in the research.

A recent article written by Richard Sams, M.D. on 15 October [1] misinforms the public, not only about stem cells but spinal cord injury research. Heralded by the headline "Christopher Reeve: An Effective Champion for an Ineffective Cause", Sams claims that Christopher Reeve believes that therapeutic cloning and embryonic stem cell research (ESCR) is "his big chance to walk again and that it holds out the only hope for other degenerative disorders of the brain and spinal cord". He points out that "to date no human trials have occurred in the field of ESCR. It's proving difficult to coax ESCs into becoming cells that could be implanted into human beings." He goes on to claim that "despite 20 years of ESCR in animals, little progress in the field has occurred. When implanted into animals, ESCs have a propensity to degenerate into tumors. No animal studies have shown any hope for patients suffering from spinal cord injuries or diseases such as Parkinson's." He then claimed that "paraplegic rats have shown dramatic functional improvement after ASC transplants. In humans Dr. Carlos Lima of Portugal is treating patients with spinal cord injuries with their own ASCs harvested from their nasal cavities. All patients treated to date have shown some functional improvement."

These statements are riddled with inaccuracies and misunderstanding of stem cells. At best, one can characterize such articles as ignorant but the blatant mischaracterization of the facts leads me to question the credentials of the author to write about the subject. This particular article not only misrepresents Christopher Reeve but also the scientific findings that support both embryonic and adult stem cell therapies. It is important that such misinformation be refuted whenever they come up. I shall try to do so here to the best of my ability. Let me take each statement in turn.

Christopher Reeve believes that therapeutic cloning and embryonic stem cell research (ESCR) is "his big chance to walk again and that it holds out the only hope for other degenerative disorders of the brain and spinal cord".

Christopher Reeve, to my knowledge, never said that therapeutic cloning and embryonic stem cell research is "his big chance to walk again and that it holds out the only hope for other degenerative disorders of the brain and spinal cord." In fact, if the author of the article had done any research on the subject, he would have found out that Christopher Reeve was as strong an advocate of adult stem cell research as he was for embryonic stem cells. For example, the Christopher Reeve Paralysis Foundation funded the work of Dr. Ira Black who showed that adult bone marrow stem cells produce neurons. Christopher was very enthusiastic about this work and told Larry King that he considered this work very promising in 2000. Christopher supported embryonic stem cell research because he thought that embryonic stem cell research was also promising. He was very concerned that federal restrictions of embryonic stem cell research were preventing such research from progressing and fulfilling that promise.

"To date no human trials have occurred in the field of ESCR. It's proving difficult to coax ESCs into becoming cells that could be implanted into human beings.

Human embryonic stem cells have not been tested in human trials because mouse feeder cells contaminate all available human embryonic stem cell lines. Federal policy prevents NIH from funding research to develop new and more suitable human embryonic stem cell lines that can be used for human therapy. To cite the absence of clinical trials as the reason why human embryonic stem cells are ineffective is at best disingenuous. Likewise, it is misleading to state that "proving difficult to coax ESCs into becoming cells that could be implanted into human beings" because many animal studies have shown that pre-differentiated embryonic stem cells can produce neural cells, including neurons, oligodendroglia, and astrocytes. These cells have been transplanted into animals and restore function in animals. It is like tying the hands of a wrestler going into a match and then saying that the wrestler is no good because he failed to win.

"Despite 20 years of ESCR in animals, little progress in the field has occurred. When implanted into animals, ESCs have a propensity to degenerate into tumors. No animal studies have shown any hope for patients suffering from spinal cord injuries or diseases such as Parkinson's."

• The author has an unusual definition of the word "progress". Hundreds of studies have reported beneficial effects of stem cell transplants in animal studies, on conditions as varied as spinal cord injury and Parkinson's disease. There is insufficient room to describe them all but three representative studies illustrate the differences.
• In 1999, McDonald [2] showed that mouse embryonic stem cells will produce neurons, oligodendroglia, and astrocytes when transplanted into injured spinal cords of rats. To date, I do not believe that any credible study with bone marrow or umbilical cord blood have produced these three types of cells when transplanted into injured spinal cords.
• In 2003, Kim, et al. [3] showed that dopaminergic neurons derived from mouse embryonic stem (ES) cells proliferate extensively and show electrophysiological and behavioral properties expected on midbrain neurons and "encourage the use of ES cells in cell-replacement therapy for Parkinson's disease."
• In 2003, D'Amour and Gage [4] found striking differences between multipotent neural stem cells and pluripotent embryonic stem cells. The latter is clearly more capable of producing different kinds of cells than the former.
• In 2004, Harper, et al. [5] reported that embryonic stem cell derived cells will form motoneurons when transplanted into rat spinal cord and not only survived but sent axons out of the ventral roots when combined with db cAMP or Rho kinase inhibitor treatments.

"Paraplegic rats have shown dramatic functional improvement after ASC transplants. In humans Dr. Carlos Lima of Portugal is treating patients with spinal cord injuries with their own ASCs harvested from their nasal cavities. All patients treated to date have shown some functional improvement."

• While it is true that two laboratories have reported some functional improvements in spinal-injured rats after transplantation of adult olfactory ensheathing glia derived from nasal mucosa, neither of these laboratories used adult stem cells. This is a mistake made by media reports and suggests that the author relies on information from television shows. Dr. Lima transplanted minced nasal mucosa into injured spinal cord. It is unclear what cells survived and contributed to recovery. Dr. Lima has yet to publish his results in any reputable journal and even he does not claim that "all patients treated to date have some functional improvement." This is a gross misrepresentation and exaggeration of the results.

In summary, Sams misrepresents Christopher Reeve, disingenuously uses the lack of human trials as an argument against embryonic stem cell research, does not know the progress in embryonic stem cell research, and exaggerates the success of adult stem cells in the treatment of spinal cord injury. Despite a more than 10:1 ratio of funding for adult stem cell therapies and the great promise of adult stem cell therapies, why haven't we cured spinal cord injury already?

References

1. Sams R (2004). Christopher Reeve: An Effective Champion for an Ineffective Cause. http://www.alwayson-network.com/comm...=P6504_0_4_0_C
2. • McDonald JW, Liu XZ, Qu Y, Liu S, Mickey SK, Turetsky D, Gottlieb DI and Choi DW (1999). Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med. 5: 1410-2. Center for the Study of Nervous System Injury, the Restorative Treatment and Research Center and Department of Neurology, Washington University School of Medicine, Box 8111, 660 S. Euclid Ave., St. Louis, Missouri 63110, USA. mcdonald@neuro.wustl.edu. Transplantation approaches using cellular bridges, fetal central nervous system cells, fibroblasts expressing neurotrophin-3 (ref. 6), hybridoma cells expressing inhibitory protein-blocking antibodies, or olfactory nerves ensheathing glial cells transplanted into the acutely injured spinal cord have produced axonal regrowth or functional benefits. Transplants of rat or cat fetal spinal cord tissue into the chronically injured cord survive and integrate with the host cord, and may be associated with some functional improvements. In addition, rats transplanted with fetal spinal cord cells have shown improvements in some gait parameters, and the delayed transplantation of fetal raphe cells can enhance reflexes. We transplanted neural differentiated mouse embryonic stem cells into a rat spinal cord 9 days after traumatic injury. Histological analysis 2-5 weeks later showed that transplant-derived cells survived and differentiated into astrocytes, oligodendrocytes and neurons, and migrated as far as 8 mm away from the lesion edge. Furthermore, gait analysis demonstrated that transplanted rats showed hindlimb weight support and partial hindlimb coordination not found in 'sham-operated' controls or control rats transplanted with adult mouse neocortical cells.
3. • Kim JH, Auerbach JM, Rodriguez-Gomez JA, Velasco I, Gavin D, Lumelsky N, Lee SH, Nguyen J, Sanchez-Pernaute R, Bankiewicz K and McKay R (2002). Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature. 418: 50-6. Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Parkinson's disease is a widespread condition caused by the loss of midbrain neurons that synthesize the neurotransmitter dopamine. Cells derived from the fetal midbrain can modify the course of the disease, but they are an inadequate source of dopamine-synthesizing neurons because their ability to generate these neurons is unstable. In contrast, embryonic stem (ES) cells proliferate extensively and can generate dopamine neurons. If ES cells are to become the basis for cell therapies, we must develop methods of enriching for the cell of interest and demonstrate that these cells show functions that will assist in treating the disease. Here we show that a highly enriched population of midbrain neural stem cells can be derived from mouse ES cells. The dopamine neurons generated by these stem cells show electrophysiological and Behavioural properties expected of neurons from the midbrain. Our results encourage the use of ES cells in cell-replacement therapy for Parkinson's disease.
4. • D'Amour KA and Gage FH (2003). Genetic and functional differences between multipotent neural and pluripotent embryonic stem cells. Proc Natl Acad Sci U S A. 100 Suppl 1: 11866-72. Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Stem cells (SCs) are functionally defined by their abilities to self-renew and generate differentiated cells. Although much effort has been focused on defining the common characteristics among various types of SCs, the genetic and functional differences between multipotent and pluripotent SCs have garnered less attention. We report a direct genetic and functional comparison of molecularly defined and clonally related populations of neural SCs (NSCs) and embryonic SCs (ESCs), using the Sox2 promoter for isolation of purified populations by fluorescence-activated cell sorting. A stringent expression profile comparison of promoter-defined NSCs and ESCs revealed a striking dissimilarity, and subsequent chimera analyses confirmed the fundamental differences in cellular potency between these populations. This direct comparison elucidates the molecular basis for the functional differences in pluripotent ESCs and multipotent NSCs.
5. • Harper JM, Krishnan C, Darman JS, Deshpande DM, Peck S, Shats I, Backovic S, Rothstein JD and Kerr DA (2004). Axonal growth of embryonic stem cell-derived motoneurons in vitro and in motoneuron-injured adult rats. Proc Natl Acad Sci U S A. 101: 7123-8. Department of Neurology, Johns Hopkins University School of Medicine, Pathology 627C, 600 North Wolfe Street, Baltimore, MD 21287, USA. We generated spinal motoneurons from embryonic stem (ES) cells to determine the developmental potential of these cells in vitro and their capacity to replace motoneurons in the adult mammalian spinal cord. ES cell-derived motoneurons extended long axons, formed neuromuscular junctions, and induced muscle contraction when cocultured with myoblasts. We transplanted motoneuron-committed ES cells into the spinal cords of adult rats with motoneuron injury and found that approximately 3,000 ES cell-derived motoneurons (25% of input) survived for >1 month in the spinal cord of each animal. ES cell-derived axonal growth was inhibited by myelin, and this inhibition was overcome by administration of dibutyryl cAMP (dbcAMP) or a Rho kinase inhibitor in vitro and in vivo. In transplanted rats infused with dbcAMP, approximately 80 ES cell-derived motor axons were observed within the ventral roots of each animal, whereas none were observed in transplanted rats not treated with dbcAMP. Because these cells replicate many of the developmental and mature features of true motoneurons, they are an important biological tool to understand formation of motor units in vitro and a potential therapeutic tool to reconstitute neural circuits in vivo.

Christopher Reeve: An Effective Champion for an Ineffective Cause

If voted into law, California Proposition 71 will require the state of California to fund destructive ESCR and cloning to the tune of $3 billion over ten years, costing California taxpayers $6 billion after interest.

PoliticalDesk | AO [AlwaysOn] | POSTED: 10.15.04 @10:59

By Richard Sams, MD

The Christopher Reeve Paralysis Foundation is one of many disease advocacy groups supporting Proposition 71, California's controversial embryonic stem cell research (ESCR) and cloning initiative. If voted into law, the initiative will require the state of California to fund destructive ESCR and cloning to the tune of $3 billion over ten years, costing California taxpayers $6 billion after interest. This astronomical sum of money is equivalent to the amount the federal government is spending on the Human Genome Project.

There are more than 250,000 persons living with spinal cord injuries in the United States and at least 10,000 new injuries each year. Since his injury, Christopher Reeve has become an outspoken advocate of persons living with spinal cord injuries and other disabilities. He has testified before the US Senate, urging members to support therapeutic cloning and ESCR. He has stated that such research is his big chance to walk again, and that it holds out the only hope for other degenerative disorders of the brain and spinal cord. Is such enthusiasm and hope justifiable?

To date no human trials have occurred in the field of ESCR. It's proving difficult to coax ESCs into becoming cells that could be implanted into human beings. Despite 20 years of ESCR in animals, little progress in the field has occurred. When implanted into animals, ESCs have a propensity to degenerate into tumors. No animal studies have shown any hope for patients suffering from spinal cord injuries or diseases such as Parkinson's.

It's another story when attention is turned to adult stem cell research (ASCR). In animal trials paraplegic rats have shown dramatic functional improvement after ASC transplants. In humans Dr. Carlos Lima of Portugal is treating patients with spinal cord injuries with their own ASCs harvested from their nasal cavities. All patients treated to date have shown some functional improvement. Two recipients of the operation, Laura Dominguez and Susan Fajt testified before the US Senate in July of this year. Both were unable to walk prior to the surgery. Now they have been able to do so with assistance and braces. A new rehabilitation center in Michigan has opened to assist patients undergoing this ground breaking procedure. Dr. Michael Levesque a neurosurgeon at UCLA School of Medicine has transplanted a Parkinson's patient ASCs into the area of brain affected by the disease. The patient who had severe Parkinson's experienced an 80% improvement in his symptoms for 4 years.

If such fruitful research is being done in the field of ASCs, why is Christopher Reeve such an advocate for ESCR? When searching the Foundation's web site there is virtually nothing on ASCR, and only a plea for supporters to urge the government to fund ESCR. Why is the foundation apparently blind to a field of research with such imminent promise for so many? We do know that biotech researchers who are standing in line to receive $300 million a year from California taxpayers have doled out nearly $5 million to help pass Proposition 71. These same researchers who have an obvious conflict of interest are exclaiming to the public that cures are just around the corner with ESCR - cures for conditions like spinal cord injuries. Leaders in the field of stem cell research without a financial interest at stake have stated clearly this is not the case. It would seem the Christopher Reeve Paralysis Foundation's vision is a bit obscured. Perhaps its members should be looking East to Portugal.

Californians need to have a clearer vision of what Proposition 71 will mean to them: further financial troubles which will line the pockets of venture capitalists, and the inroads for cloning human beings.

Richard Sams, MD is an Adjunct Assistant Professor of Family Medicine for the Uniformed Services University Health Sciences, and is on faculty at the Naval Hospital Camp Pendleton Family Medicine Residency Program in Oceanside, CA. He serves as the lead consultant of the Ethics Committee, and is a Master's Candidate in Bioethics at Trinity International University.

[member412678]

Thanks for posting this Dr. Young. What is really upsetting to me is when the SCI community themselves encourage these people by claiming we already have the cure and/or make comments against ESC and SCNT research. If people in our own community don't get it, then how can we expect the general public to?

[Faye]

Dr. Young,

Can you put out a Press Release, refuting Dr. Sams statements?

Or at the very least have your write-up published in the mainstream media?

I have suggested in an earlier thread that Susan (who's improvements from Dr. Lima's procedure keeps being used as proof that ESCR is not necessary), put out a press release of her own, stating that she does not consider the nasal mucosa transplant procedure a Cure, and that she continues to look toward any and all other options to find the cure she is looking for ( including ESCR ).
What do you say Susan?

~It's troubling that exit polls and vote totals were so far out of whack. "I've spent my whole life in marketing. The difference is clearly beyond any sampling variability. ... The community of statisticians and media experts need to not let this be dropped"~ Bill Hawkes, a retired A.C. Nielsen Co. statistician.

[Wise Young]

Hope,

I spoke at a fundraiser called Caroline's Hope last night. That event hit me in the stomach. Caroline is a 2 year old baby who suffered a high cervical spinal cord injury. She is on a respirator. They showed a video from the Miami Project that showed Caroline, Marc Buonicanti, and Wendy Crawford, expressing their hope for a cure. I pointed out that I have known Marc Buonicanti and Wendy Crawford for over 10 years and that it is too long. As Christopher Reeve once pointed out, he can understand if the scientific obstacles were the reason why we do not have a cure but he cannot tolerate it when the reasons are money and politics.

We must redouble our efforts and make it happen. We have been complacent for too long. Spinal cord injury has been put on the backburner too long. I believe that it is essential that the funding and political roadblocks be removed. If our federal government will not do it, we must find another way.

Wise.

[Wise Young]

Faye,

I have thought a lot about this. My goal is not to convert people like Sams. There will always be more like him. My goal is to prevent these articles from disheartening the spinal cord injury community and to give our community ammunition to refute these arguments. Attacking other people's views will only generate heat and take up time that I don't have. My preference is to spend all the press time that I can get emphasizing positive actions rather be negative. I am already distressed that the elections and all the refuting negativity has taken up so much of my time and energy.

Wise.

[Faye]

Originally posted by Wise Young:

Faye,

I have thought a lot about this. My goal is not to convert people like Sams. There will always be more like him. My goal is to prevent these articles from disheartening the spinal cord injury community and to give our community ammunition to refute these arguments. Attacking other people's views will only generate heat and take up time that I don't have. My preference is to spend all the press time that I can get emphasizing positive actions rather be negative. I am already distressed that the elections and all the refuting negativity has taken up so much of my time and energy.

Wise.

Dr. Young,

I agree with you that it is a shame valuable time is diverted back and forth on assertions and counter assertions rather than it being spent on the actual research.

But since you often eloquently help CC understand some of the fallacies of the excessively negative assertions, wouldn't it make sense to at least have a fact sheet/ Press Release with a link to a website, going out to the reporters which they could use the next time they write an article?

OR, if we could get your permission to post your response above on the www.CureParalysisNow.org site, I think it would be very helpful to direct reporters to our site. I love CC as a source for info, but for reporters with time constraints it may be too hard for them to find the info they need if we direct them to CC.

Please let us know if it would be ok to post this particular response of yours on the Cure Paralysis Now site.

Thanks,

Faye

~It's troubling that exit polls and vote totals were so far out of whack. "I've spent my whole life in marketing. The difference is clearly beyond any sampling variability. ... The community of statisticians and media experts need to not let this be dropped"~ Bill Hawkes, a retired A.C. Nielsen Co. statistician.

[poonsuzanne]

Originally posted by hope2findacure:

Thanks for posting this Dr. Young. What is really upsetting to me is when the SCI community themselves encourage these people by claiming we already have the cure and/or make comments against ESC and SCNT research. If people in our own community don't get it, then how can we expect the general public to?

Dena,

I like to call you Dena as your name sounds so sweet and pretty to me.

Precisely, I second every single word of what you have just said.

Suzanne

[poonsuzanne]

Faye,

Thanks a lot for doing so much for us, the worldwide SCI community!!!

Suzanne

[This message was edited by Suzanne Poon on 11-15-04 at 09:07 PM.]

[Wise Young]

Faye, you of course have my permission to post anything that I write (maybe I better be more careful about what I write ) on your web site as long as it is properly attributed to CareCure. Wise.

[PapaJoe]

Wise,
I understand your dismay regarding the Media's inaccurate reporting of ESC's promise and potential. I know we have been hindered in the U.S. by these misinterpretations but I was just wondering if the Chinese, who are blessed with the ability to study and experiment with ESC have any findings we could use to our advantage?
Thank you,
PapaJoe