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Medical Forum / Diseases and Disorders / Epilepsy / July 2005

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Stem Cell research and the cure for epilepsy.

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FranX - 25 Jun 2005 10:45 GMT
Hello all,

I am one of many who is looking for that cure. I have TLE and it's
somewhat controlled but has drastically affected by quality of life -
turning me into a lonely hermit.

Regardless, does anybody have any information on this status. Beyond
the ethical, religious debate - Just straight facts on whether stem
cell research can indeed be the cure we are waiting for?

I've read some positive documentation on stem cell tests on rats
(obviously they are rats). My doctor wants me to get surgeory, but if
this is true and a medical breakthrough is happening - i'd rather stick
it out. And if it is true what is the exact process of "replacing" or
"repairing" our brain in terms of stem cell use?

Thanks for listening.
G.Ross - 25 Jun 2005 17:06 GMT
> Hello all,
>
[quoted text clipped - 13 lines]
>
> Thanks for listening.

If it's the article I'm thinking of, the regeneration of 'stem cells'
(done in Germany?) was at the level of skin, or muscle structure to repair
burn damage.
  It's a long way from something more advanced like e.g. an organ like a
liver or kidney, and 50? years from even doing parts of a brain stem, if
that proved to be feasible.
  So far as I could tell from some programs I've watched on what they're
experimenting with,  changing a part of the Brain with a 'new improved part'
would be analogous to replacing a 'spark plug'  on a Jetliner somewhere over
the Atlantic at 30,000 feet, without interrupting the flight controls.

Granted they probably thought transplanting e.g. a Human Heart 50 years ago
was long long away.

 But parts of our brain are more complex?  than e.g. a Heart Valve, a
kidney or other organs.    So far as I know Brain cells don't 'regrow'  like
some other organs might?   *That might be what they're hoping for with Stem
Cells.
  I'd still be surprised if they came up with a way to 'control'  the
growth or regrowth of,  example--  one of the Temporal Lobes -- e.g.  what
would make the stem cell grow a Temporal lobe and not decide we 'needed'  a
third Frontal Lobe,  another eye, or improved hearing once it is 'started
up' ? Maybe they will find 'the code' for what will guide reconstruction.
DNA wasn't known about (much) in 1950s.  But I still think we're talking
about times measured in multiples of decades to centuries, versus months.

  (I have Right Temporal Lobe-based epilepsy, by the way, so it's not just
someone who doesn't have seizures suggesting one possibility. We do have 4-5
people who might still be reading the group who have had Temporal Lobe
surgery, who might be able to tell you what it involved, if they had any
negatives about before or after the surgery, and *whether they'd do it
again.   They might be more  skilled at telling you of any pluses or minuses
that they encountered and how they're doing.   The impression I had was that
the ones who were posting here, all had positive (improved) outcomes and
their seizures had gone away.  )

    How Often do you have seizures?   Have you tried the multiple types of
pills that are available for Temporal Lobe seizures already?  (You didn't
say on first post, so I can't tell if you've already exhausted those, or
not.   I tried 3 pills over ~2-3 years, then had mine under control.   Last
one I had was June 98, but I still use the pills.  That's easier (for me)
than letting a Doctor go through the roof of my mouth to find which parts he
wants to cut out...  )

 Our hospital and medical schools are already getting near the capacity of
students they can handle now, as the population continues to outpace the
available number of spaces for new students.  One place there will be
shortages next will be in caregivers and medical staff, as us 'baby boomers'
reach mid-60s and start to retire.

 If I find any sites (from my weekly Radio Science Show) on Stem Cell
links,  I'll post them for you.  Did you try searches on 'Stem Cell
Research' or Health and Stem Cells ?  If there was chance of this being
available in next 10 years, there'd probably already be articles in New
Scientist? (is that the uk science Magazine?)  or Discover (that's one of
the N. American ones).  I think National Geographic had a special issue
about a year? ago on 'future research' too?  G./
Mike H - 30 Jun 2005 01:48 GMT
I have Right Temporal Lobe Epilepsy. I developed it about 20years ago. I
am now 52 years old and on SSD. My seisures have not improved over the
years. I have tried just about ever med that is out there. I have had
the VNS and as a last result I had surgery. To make a long story short
that didn't work either. About 2 days after the surgery I had a stroke.
I have recovered from that but the seizures keep on coming. I did not
get them from a hear injury or any family history. I just woke my wife
up in the middle of the night. She called EMS and as soon as he came
into the bedroom he asked her if I had Epilepsy. THen we went to the
hospital and I'm sure everyone knows what hapened after that. My yongest
son tells me that one day they will find a cure so keep praying and
don't give up hope.                                Mike  H.
Darwin - 25 Jun 2005 20:02 GMT
> Hello all,
>
[quoted text clipped - 13 lines]
>
> Thanks for listening.

The study of the use of stem cells to treat epilepsy has only just begun.
There are a few early positive studies in rodents that are laying the
groundwork but it will be a long time in coming for a real treatment based
on these techniques.  Right now they seem to be trying to increase the
number of functional GABA-producing cells which are the main inhibitory
cells in the brain.  The theory here is similar to the use of anticonvulsant
drugs in that the cause of the seizures is not being addressed by
essentially shutting down the brain (i.e. increasing the seizure threshold).
Unfortunately, for most epilepsies, the cause is not known or understood.
Even the most basic sign of a seizure...epileptic discharge...is not
understood.  I attended a seminar yesterday on "What is epileptic
discharge?" and researchers are not sure what it is or how it is triggered,
maintained or even stopped.  Until we can hope to understand what a seizure
is and what determines its threshold at a cellular level, I don't believe a
truly effective "cure" can be found.

1: Neuroscience. 2005;133(4):1029-37.

Genetically engineered cells with regulatable GABA production can affect
afterdischarges and behavioral seizures after transplantation into the
dentate
gyrus.

Thompson KW.

VA Greater Los Angeles Healthcare System/UCLA Department of Neurology,
Building
114, Room 137, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA.

Intractable seizures originating in the mesial temporal lobe can often be
controlled by resection. An alternative to removing hippocampal tissue may
be
transplantation of GABA-producing cells. Neural cell transplantation has
been
performed in hundreds of patients, including some with temporal lobe
epilepsy.
This study evaluates the seizure-suppressing capabilities of engineered
GABA-producing cells transplanted into the dentate gyrus. Immortalized
neurons
were engineered to produce GABA under the control of doxycycline. The cells
were
characterized for GABA production in vitro and for their ability to raise
GABA
concentrations in vivo. Cells were transplanted bilaterally into the dentate
gyrus of rats and tested in two separate paradigms. Afterdischarge
thresholds
and durations were tested with granule cell stimulation, and the development
of
behavioral seizures, induced by daily electrical stimulation of the major
excitatory input pathway into the dentate gyrus, was assessed in the
presence,
or the absence, of doxycycline. GABA production was under the tight control
of
doxycycline. Cells engineered to produce GABA raised tissue GABA
concentrations
in the hippocampus compared with non GABA-producing cells, and this was
abolished when doxycycline was administered. GABA-producing cells raised the
threshold, and shortened the duration of hippocampal afterdischarges
elicited by
granule cell stimulation. Lastly, the appearance of stage 5 seizures was
slowed
in the kindling paradigm, compared with a group that received
non-GABA-producing
cells, and compared with a group that received GABA-producing cells but was
administered doxycycline. This study shows that targeted hippocampal
implants of
genetically engineered cells have the potential to raise GABA levels and to
affect seizure development. The ability to suppress the production of GABA,
and
to modulate the physiological effects of the transplanted cells provides an
important level of experimental control. These techniques, combined with
stem
cell technology, may advance cell-based therapies for epilepsy and other
diseases of the CNS.
G.Ross - 26 Jun 2005 15:10 GMT
>> Hello all,
>> I am one of many who is looking for that cure. I have TLE and it's
[quoted text clipped - 28 lines]
> triggered,
> maintained or even stopped.
***** You might find some articles of interest if you do a search on
'epilepsy & kindling' -- the latter is the term for how some of the seizure
types might start with a minor electrical 'flicker'  then increase and
increase (kindle)  to the point where a full seizure is triggered.   I don't
know if that's restricted to one or 2 of basic szrs. or if it's related to
how most seizure types might kickstart and spread to a full-blown seizure.
But it's a term you might not usually go searching for.  Note that many of
the articles you pull up might be Medical Level in nature and not written as
a 'reader's digest' format for general reader (our) consumption.   But if
you want it that detailed, that's a search topic you could try.

 (I cut? some of GABA etc. article you quoted, as kindling etc. topic is a
different source of seizures and may not relate to chemicals within a
person's brain and other 'stuff'.   *Much of this 'stuff'  is Neuroscience
that most of us aren't trained to interpret, and pulling them in on searches
to 'cure ourselves', is as workable as transplanting our own organs.  Just
my opinion. )  G./

 Until we can hope to understand what a seizure
> is and what determines its threshold at a cellular level, I don't believe
> a
[quoted text clipped - 17 lines]
> performed in hundreds of patients, including some with temporal lobe
> epilepsy.

**G.*  I don't know which part is the 'mesial temporal lobe'.   There are 2
temporal lobes, left and right above the mouth behind the cheeks.   My szrs.
start in the Right T. Lobe.  The symptoms of the Left T.Lobe are different
at onset than right side.  I've never heard *Mesial used in the same
sentence as the T.Lobes and think it might be a different part or section of
the brain? But I'm not a surgeon. And we're *all glad about That! :-<  ) /

> This study evaluates the seizure-suppressing capabilities of engineered
> GABA-producing cells transplanted into the dentate gyrus. Immortalized
> neurons
> were engineered to produce GABA under the control of doxycycline.
**** What is an **Immortalized Neuron ???? All our Neurons die and are
regenerated? during our lifetime. Skin cells etc. do too.  New Cells are
generated within our biology -- but they're New Cells our bodies produce,
and not 'Reborn' or 'Immortalized'?     Without being a Neuro-Surgeon, I
wondered if this is written by someone not in that field, but I could be
wrong.  Just suspicious of  'this is the (one) cure  !!! :-o   Send a
check...'   /
***** Below is quoted out of a medical site or journal, and except at end
(sarcasm part) I didn't comment on it.  It is meaningless to me for my level
of 'support' wrt. this group.   /

The cells
> were
> characterized for GABA production in vitro and for their ability to raise
[quoted text clipped - 20 lines]
> elicited by
> granule cell stimulation. Lastly, the appearance of stage 5 seizures was

*** I don't know what's a Stage 5 seizure?  So this is meaningless for 'us
peons' if it skips on to year 3 of medical school in mid article??  Unless
we knew what a stage 5 seizure is and how it related to our own experiences,
the 'kindling paradigm' becomes meaningless below ??   Except I gave a lay
definition of what Kindling was above.  /G.

> slowed
> in ***the kindling paradigm***, compared with a group that received
[quoted text clipped - 14 lines]
> other
> ***diseases of the CNS.

G.  (Epilepsy is now a 'disease' of the Central Nervous System?  New
breakthrough- your Heart Murmur is a Disease...  *My interpretation of above
paragraph (in english) is that treatment with some types of (gaba) chemicals
can increase the szr. threshold (reduce the risk of *some types of our
seizures), but that other chemicals introduced, or that our bodies might
**produce, would defeat that improvement and render the gaba chemical
ineffective?  --> that's the part 8 lines up where it talks about
"modulating and providing a level of experimental control"--  inside **s ?
   None of above appeared related to original thread wrt. Stem Cell
Research?
  Or were Gaba cells (I don't know) part of current Stem Cell Research?

  I thought Gaba biology was older and not related to 'stem cell research'
which Generates new Tailored Cells for Organ or Blood Regeneration in people
with compromised immune/blood systems --eg. by HIV, or Cancers--versus
***Biologic Engineering at the extreme, where they thought they *might be
able to Rebuild a custom Heart, Thyroid, or Kidney, based on a person's or
relative's  particular **Stem Cells, that wouldn't be rejected if they were
then Re-transplanted into the 'Client Recipient' (the donor was the
receiver?).   I was under the impression (mine) that the excitement within
the Medical community about Stem Cells etc. was that some of the treatments
offered reduced risks of rejection by the recipient, versus eg. Transplants
from others.

   It *Also was thought that some of the Groups and Religions etc. who
currently don't approve of Transplants, or transfusions etc. from Others,
might be ammenable  to Organs, Repairs and Blood that was Sourced directly
from the person who would benefit from the 're-engineered'  products.  In
other words, I* would be the source of *my replaced parts.  (Brain parts and
organs are still potentially 100s of years away.)   Whether those 'products'
are still viewed as 'foreign'  within those beliefs or religions is subject
of another topic (and group?) than here....   G./
CyberCafe - 27 Jun 2005 02:03 GMT
>>>Hello all,
>>>I am one of many who is looking for that cure. I have TLE and it's
[quoted text clipped - 77 lines]
> sentence as the T.Lobes and think it might be a different part or section of
> the brain? But I'm not a surgeon. And we're *all glad about That! :-<  ) /

Mesial refers to the center or the middle of something.  Earlier today,
I looked around the net for a picture or something to show where that
area would be without luck.  I can't really tell from text descriptions
if it means more toward the core of the brain (hippocampus).

>>This study evaluates the seizure-suppressing capabilities of engineered
>>GABA-producing cells transplanted into the dentate gyrus. Immortalized
[quoted text clipped - 96 lines]
> are still viewed as 'foreign'  within those beliefs or religions is subject
> of another topic (and group?) than here....   G./
Darwin - 29 Jun 2005 02:05 GMT
>>> Hello all,
>>> I am one of many who is looking for that cure. I have TLE and it's
[quoted text clipped - 40 lines]
> (our) consumption.   But if you want it that detailed, that's a search
> topic you could try.

The kindling technique to generate seizures in animals has been seriously
studied since the 1960s.  As said above, it involves electrically
stimulating a region of the brain with very low-intensity current repeatedly
triggering a focal seizure until a generalized seizure is triggered.  Each
seizure is thought to change the brain, permanently lowering seizure
threshold.  The technique is currently used to test new drugs for complex
partial seizures as well as to examine the changes in the brain resulting
from seizures.  It was originally thought to model the development of
post-traumatic epilepsy, with brain damage triggering repeated undetected
focal seizures until generalized seizures start.

>  Until we can hope to understand what a seizure
>> is and what determines its threshold at a cellular level, I don't believe
[quoted text clipped - 26 lines]
> section of the brain? But I'm not a surgeon. And we're *all glad about
> That! :-<  ) /

As someone here already mentioned, mesial is basically another word for
middle or medial, referring to "towards the middle".  Mesial temporal lobe
sclerosis is thought of as the defining anatomical change in the temporal
lobe in temporal lobe epilepsy.  It's still not clear if the changes seen in
the temporal lobes are the cause or the result of seizures.  I actually
think that the sclerosis is the result of seizures and not the cause.

>> This study evaluates the seizure-suppressing capabilities of engineered
>> GABA-producing cells transplanted into the dentate gyrus. Immortalized
>> neurons
>> were engineered to produce GABA under the control of doxycycline.

> **** What is an **Immortalized Neuron ???? All our Neurons die and are
> regenerated? during our lifetime. Skin cells etc. do too.  New Cells are
[quoted text clipped - 3 lines]
> wrong.  Just suspicious of  'this is the (one) cure  !!! :-o   Send a
> check...'   /

Dividing cells in a dish have a tendency to stop dividing and become their
final form (e.g. neuron).  Immortalization is a technique whereby the cells
are made to divide forever essentially, until a signal is given to tell them
to stop dividing and become their final form.  The stem cell lines that are
used in stem cell research are immortalized cell lines so that they can
continuously generate more stem cells for research or therapeutic purposes.
They used the term "immortalized neuron" which I don't think I'd use.  They
likely meant immortalized cells that produce neurons.

The neurons in the brain are in their final form and don't divide to produce
more neurons, which is why the brain doesn't repair itself to any great
extent.  There are some areas of the brain that contain dividing stem cells
that continually generate new neurons for specific purposes.  One of these
areas is the hippocampus in the temporal lobe.  Researchers are trying to
manipulate these adult stem cells to repair the brain after injury.

Other types of stem cells have been discovered in blood, skin and even in
the eye.  Researchers are attempting to manipulate these stem cells so they
can be transplanted into damaged organs and repair the damage by replacing
specific lost cells.  These adult stem cells are not as "flexible" as
embryonic stem cells and have a limited ability to become cell types other
than those that they were originally destined to become.  On the other hand,
embryonic stem cell are very flexible and can potentially become any cell
type in the body.

There are several problems with stem cell technology at the moment.  For
example: 1) How can you be sure they stop dividing in the brain and don't
become a tumor?  2) How can you be sure the new neurons generated are the
correct type and function in the correct way?  3)  The survival of
transplanted cells is very low.  How can survival be increased?

> G.  (Epilepsy is now a 'disease' of the Central Nervous System?  New
> breakthrough- your Heart Murmur is a Disease...  *My interpretation of
[quoted text clipped - 7 lines]
> Research?
>   Or were Gaba cells (I don't know) part of current Stem Cell Research?

Researchers/clinicians use the terms disease and disorder interchangably.
When I first heard of epilepsy described as a disease, I looked up the word
disease in a medical dictionary and saw the word disorder as part of the
definition and vise versa.  I had thought that disease included
transmission, but this is not necessarily the case.  For example,
Parkinson's Disease is also a disorder of the nervous system.

The study perfectly exemplifies the use of stem cells to treat disease.  One
of the theories of temporal lobe epilepsy is that GABA-producing cells die
and that this results in lowered seizure threshold.

The main points of the cited study were that:

1) A model of epilepsy was used. (i.e. kindling for complex partial
seizures)
2) Cells that make inhibitory chemicals (i.e. GABA) were transplanted into
the brain.
3) The transplanted cells made seizures less likely.
4) The amount of inhibitory chemical could be regulated by the experimenter.

The last point is very useful since if too much GABA is generated this could
simply shut down that part of the brain and impair thinking or whatever else
that part of the brain is responsible for.

Much of the anticonvulsant drugs enhance the GABA systems of the brain in
order to raise the seizure threshold and make seizures less likely.  The
study is basically getting a bunch of cells to do that within a potential
seizure focus, as well as allow the amount of GABA they make to be
controlled.  These are the kinds of things that have to be addressed in all
stem cell therapies.

>   I thought Gaba biology was older and not related to 'stem cell research'
> which Generates new Tailored Cells for Organ or Blood Regeneration in
[quoted text clipped - 7 lines]
> some of the treatments offered reduced risks of rejection by the
> recipient, versus eg. Transplants from others.

The reduced risk of rejection is important but not the most exciting thing
about stem cell therapies since immunosuppressant drugs are currently able
to keep rejection in check (at the risk of infection).  The exciting thing
about stem cell technology is that very specific types of cells can be
replaced, thus "repairing" an organ.  For example, Parkinsons disease
results from the death of a type of cell that produced the chemical dopamine
in a specific part of the brain.  Stem cells could potentially repopulate
the lost dopamine neurons in that part of the brain, perhaps "curing" the
disease.  A true cure, however, would address understanding what caused
those cells to die in the first place.

>    It *Also was thought that some of the Groups and Religions etc. who
> currently don't approve of Transplants, or transfusions etc. from Others,
[quoted text clipped - 4 lines]
> 'products' are still viewed as 'foreign'  within those beliefs or
> religions is subject of another topic (and group?) than here....   G./

Yes, the exciting things about adult stem cells are 1) that there wouldn't
be a rejection problem, 2) they can regenerate many parts of the body, and
3) they might be easily accessible (e.g. from blood or even skin).   The
main problem is just getting them to become the types of cells you want them
to become.  It seems to be a lot more difficult to do this than with
embryonic stem cells.
G.Ross - 26 Jun 2005 20:19 GMT
I found this article (without going to google) -- it talks about some places
stem cells could be of use, and another link suggests that Lou Gerrig's
(sp?) might be treatable by some therapies.  But neither this article nor
the other of these 2 mentioned *epilepsy **anywhere.   Article pulled in was
at http://www.medicalnewstoday.com/medicalnews.php?newsid=26541#  .    I
hope I recorded that correct.  If not it was in Medical News and I searched
for topic 'stem cells'.   G./

> Hello all,
> I am one of many who is looking for that cure. I have TLE and it's
[quoted text clipped - 11 lines]
> "repairing" our brain in terms of stem cell use?
> Thanks for listening.
G.Ross - 26 Jun 2005 20:31 GMT
 Note an article in Newsweek, is listed down side of article at site I
posted below.

 You can read it if you want, but it said that *that one was a Trail
Article before **Subscribing to Newsweek online.  I didn't bother with that
article.    I get enough magazines already without adding a new one I
couldn't keep up with .
  I think once you're at the site, you can roam around within the
originating site's articles if there were more, but I didn't go on to see if
there were other related articles.
  *Most of the other sites I've gone to, like **GOOGLE, list "RELATED
SITES"  at the bottom, if it found others.  *This one I listed below didn't.
fyi.    G./

"G.Ross" <> wrote in message ...
>I found this article (without going to google) -- it talks about some
>places stem cells could be of use, and another link suggests that Lou
[quoted text clipped - 4 lines]
>I recorded that correct.  If not it was in Medical News and I searched for
>topic 'stem cells'.   G./
Darwin - 27 Jun 2005 18:25 GMT
There's an article on stem cells in the current Scientific American.  I
haven't read it yet but it seems to be free.

     Mother of All Cells
     Scientists expect enormous benefits for humankind from the surge of
research on embryonic stem cells. But it could take a generation or two
before the full impact is felt. Clive Cookson discusses the issues

http://www.sciam.com/article.cfm?articleID=000AA485-7635-12B8-B5AE83414B7F0000&p
ageNumber=1&catID=9


>   Note an article in Newsweek, is listed down side of article at site I
> posted below.
[quoted text clipped - 19 lines]
> >I recorded that correct.  If not it was in Medical News and I searched for
> >topic 'stem cells'.   G./
G.Ross - 02 Jul 2005 16:17 GMT
>I found this article (without going to google) -- it talks about some
>places stem cells could be of use, and another link suggests that Lou
[quoted text clipped - 20 lines]
>> "repairing" our brain in terms of stem cell use?
>> Thanks for listening.

  I just looked at a National Geographic that arrived here ~Friday last.
They should be in libraries which get them, soon.   It's the July 2005
issue, and has cover page "Stem cells How far will we go?"
  I don't know if there's access available via
http://nationalgeographic.com/magazine  listed on the cover.   It might want
a Member number to open any pages online (i.e. showing you subscribe), or
not.  It starts with debate over ethics of using Embryonic stem cells since
(according to article)  after a certain phase of development, while the
*early stem cells may be usable wrt developing many types of organs or
functions,  after a certain point of development within an unborn child,
they appear to specialize early and from that point on, only appear to work
for parts of immune systems or specialized functions and not a 'smorgasbord
cell'  to develop multiple uses **after that point.
   A cursory glance through the rest of the article makes no mention of
brain stem or cell redevelopment or brain repair functions, and nothing
about e.g. epilepsy in the content.     G./

 
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