February 2009, SCS Newsletter…..
GERON CORPORATION SCI HUMAN TRIAL WITH EMBRYONIC STEM CELLS & SCS RELATED
WORK
Within days after President Obama took office, the FDA approved using a few stem cell lines from those authorized by
President Bush and 2001. This was soon followed by Geron Corporation’s announcement of a new human trial with
embryonic stem cells. They have done related experiments on animals for years. To date, Geron claims to have spent
170 million in preparation for this. Some 10 human patients in at least four different medical centers could be treated
this coming summer.
Although these new embryonic stem cells were approved for human use and 2001, this trial has taken until now because
of opposition and because of several Bush vetoes against any rule changes. The FDA had been hesitant to give
approval unless sure of presidential approval.
The new gear on human trial claims to be the first embryonic stem cell trial on human spinal cord. The patients will be
completely paralyzed somewhere between C-3 and T-10 for 7 to 10 days (acute – subacute). The cells will be from
discarded embryos from fertility clinics and of the type called oligodendrocytes, those cells producing nerve fiber
insulation called myelin. They will be injected directly into the injury site. Geron rat experiments have shown that they
only remyelinate axons but cause neither axon growth or tumors.
Is a phase 1 trial to first make sure no harm is done; a secondary goal is to detect any restored function such as bladder
and bowel. The delay until summer is said to be because Geron had to wait for FDA approval, and freedom from Bush
restrictions. They will also have to train researchers on both how to do the injections and read MRIs in a uniform way of
so has to insure accuracy and consistency among participating medical centers.
The big attraction of embryonic stem cells versus adults stem cells is that they can more easily become any of the
bodies 200 cell types and because they may be highly effective. Also, their production from embryos is almost
unlimited. The risk, of course, is immune rejection in patients because the embryonic stem cells will, by definition, be
from other individuals.
Many researchers are enthusiastic over this new trial when a number are not. For one thing, to avoid a strong immune
reaction Geron has carefully restricted their treatment cells to only rather well-developed progenitor precursor
oligodendrocytes. Thus, this treatment hopes to avoid any immune reaction by supposedly making the central nervous
system more “privileged”. But this may only delay an immune reaction. Some researchers fear rejection will eventually
occur anyway and become a big problem including teratoma tumors in the cord etc. This new trial is not a chronic
treatment though it could, if safe, be used in a chronic injury if that old injury were first mate acute (part of our strategy).
Finally, to date the most success in human treatment of various kinds has been via use of adult, not embryonic cells.
RELATION TO SCS R&D
Many years ago SCS was among the very first to stress that chronic, not acute, SCI treatments were the first thing to
concentrate on for two reasons: 1- 99% of us weren't hurt the last few hours or days ago, and are therefore old,
chronic, not new, acute injuries. 2- Because of this narrow time window, inflammatory reactions, loss of key nerve cells,
acute shock, etc.. acute treatments don't work. Supporting evidence has accumulated. Many years of various acute
treatment trials on thousands of patients with inflammatory suppression drugs have failed. Further, to avoid any
possible rejection SCS has stayed with autologous adult cells. Who wants to be full of immunal suppressant drugs?
So far, the SCS strategy has been verified. Gently making an old and stabilize chronic injury acute again to achieve a
chronic cure is a far more natural, safe, and sensible, approach. For one thing it's not a crash program under
emergency conditions. Instead, there is time to carefully plan and execute the treatment. Nevertheless, Geron's going
forward should help because: 1- It will inspire more efforts and break the ice, and 2- Even failure will only reinforce the
SCS rationale.
So, what will we get out of it? SCS has already published our results on scar control. Results on our other cure
components will soon follow. Since 2002, the strategy of the SCS center as been to refresh the injury and remove the
barriers to growth and a repair prior to using any transplants, nerve growth factors, and electrical stimulation. The
underlying rationale is that the surest, safest, and gentlest route to care is to ignite the body's own natural healing
potential rather than forcing it by potentially damaging quick fixes. At this point our success is well documented with
respect to the safe removal of the scar and also the retardation of a secondary scar. And, we have been successful
stimulating neuromuscular re-function in an engineered transplant via electrical stimulation of the already remaining
central pattern generator in the spared cord of chronic rats. So far, are combination has gotten up to 30% re--function
in already stabilized chronic -- not acute -- rats. So, we have established a protocol, or recipe, for a treatment
procedure which could, should the need arise, be easily adapted for embryonic stem cells. And, it has all been done by
using adult stem cells. The refunction achieved, although significant, is still not yet a return to full normal function but it
seems to be far better than anyone else has ever gotten in complete chronics. Therefore, we are busy attempting
further improvements.
By 2005 SCS had already recognized the possible importance of oligodendrocyte precursor cells. Development of this
type of cell (while not affecting our main adult cell line) has been a good idea, but so far hasn't seemed necessary. But
in case it might be SCS has already successfully developed and oligodendrocyte stem cell line for use in our lab and
could easily began a small pilot trial using them in our own treatment paradigm. So, using transplantation of
oligodendrocyte precursor cells containing a growth friendly matrix, scar ablation, pharmaceutical therapy, and TANES
(electrical CGP stimulation), can easily be done by the SCS lab.
If Geron's ESC treatment causes rejection problems the hope is that the degree of these problems could, possibly, the
relatively small if the ESC effectiveness is significant enough. Should it come to that the forethought we had to also
prepare oligodendrocyte cells for a chronic trial in our own animal model could eliminate a great deal of preparation time
in using them. Thus, although we cannot predict success or failure using this cell type, we have anticipated their use
and now also their humanization. So, if ESC oligodendrocytes proved to be very effective, and more important, safe,
then we do will be ready to go.
What the Geron trial will likely illustrate once again is that SCI is a complex injury requiring not one single magic cure
bullet like a vaccination (which, of course, triggers a cascade of protective immune combinations itself) but a careful
reconstructive combination of cure treatments. Simply injecting one cell type and hoping for the best may not cut it
because it doesn't deliver scar reduction or stimulation via either pharmaceutical or electrical rehab therapy, or both.
We'll just have to see. Anyhow Geron has done a lot of work and deserve great credit.
After more than 30 years SCS remains virtually the only SCI organization attempting to treat SCI for what it is, a
combination injury. Others have come and gone making big promises or hunting magic bullets and wasting millions and
years leaving only a record of failure. Why is this? Because people love magic, glitz, big promises, the big and shiny,
and so ignore the trap of second agendas. SCS makes only the promise of an honest effort on the actual problem as it
is, we have no hidden separate agenda such as fattening the paralysis status quo, blind alleys such as building
academic careers on paralyzed bodies, rackets, or building more rehab centers. SCS doesn't sell magic. In short, we
must address the problem confronting us not a separate and possibly destructive agenda.
As Barnum said,"there's a sucker born every minute." Glamor sells but doesn't last. Only a few have understood this
and we thank them. And only a few is probably all there ever will be, that's the fate of pioneering. But pioneering is
where breakthrough production is. The Geron work is an example.
Compare the SCS record with any other. But while we're for the Geron works and similar efforts they remain single
bullet oriented because they must first show corporate profits. That's the purpose of corporations. There is much less
quick profit in all that's required for a comprehensive cure. Still, if they've already spent 170 million on this may be
they'll forge ahead with a more comprehensive cure. No one yet knows. What we do know is that there have been and
still are massive forces opposing medical progress from huge corporations selling the status quo to the government they
control. That has been amply shown. -- --CEC