Date: Mon, 06 Jan 2003 14:39:53 -0000
Subject: [StemCells] Spinal Cord Injury Recovery - Rats

Damaged nerves in the spinal cord usually form a dense scar, making
it difficult for nerves to regenerate and cross it. These scars
contain certain molecules, including ones called chondroitin sulphate
proteoglycans (CSPGs). CSPGs inhibit neural growth both in vivo (in
live animals and human beings) and in vitro (in lab-grown cells). A
bacterial enzyme, chondroitinase ABC (chABC), is able to remove
certain parts of the CSPG molecules. In doing this, the inhibitory
activity of CSPG can be decreased. A research team made up of
scientists from various universities in England recently treated rats
that had spinal cord injuries. They delivered the enzyme chABC to the
rats' spinal injuries. They found that in response, a protein known
to help regenerate neurons began to be produced in the injured
neurons. Also, the treatment promoted the regeneration of neurons in
the rats, above and below the spinal injuries. In addition, there was
functional recovery of some movement: the disabled rats recovered a
regular gait. Says scientist Elizabeth Bradbury, "It shows the cells
above the lesion[s] are talking to those below." Such research shows
that, to treat spinal cord injury, legitimate & ethical forms of
research abound and are making great strides towards treating
neuropathies. [Bradbury, E.J., et al, "Chondroitinase ABC promotes
functional recovery after spinal cord injury," Nature 416, 636-640
(2002); Pearson, H., "Spinal cord recovery hurdle cleared: Bacterial
enzyme chews through nerve growth barrier," Nature "Science Update,"
11Apr02; Report 31, 202-289-2500;

As for ALS (see post in Dec. 2002 where currently human trials in
Italy) one would need not only to heal the cord but protect it from
further injury.

Date: Mon, 06 Jan 2003 14:10:39 -0000
Subject: [StemCells] Treating Parkinsons w/Adult Stem Cells
Treating Parkinson's with Adult Stems Cell and Other Alternatives
Using adult neural stem cells, Dr. Michel Levesque, at the Cedars-
Sinai Medical Center in Los Angeles, reports a total reversal of
symptoms in the first Parkinson's patient treated. The patient, a 57-
year old former fighter pilot, is still without symptoms three years
after the adult neural stem cells were removed from his brain, coaxed
into becoming dopamine-producing cells, and then reimplanted. Because
the stem cells came from the patient, there was no need for
immunosuppression to overcome rejection. "I think transplantation of
the patient's own neural stem cells and differentiated dopaminergic
neurons is more biologically and physiologically compatible - more
efficacious and more elegant," said Levesque. In addition to its use
for Parkinson's, the technique is under study for juvenile diabetes,
stroke, brain tumors, spinal cord injury, and other conditions.

Reference
Results presented April 8th, at the meeting of the American
Association of Neurological Surgeons.

Retinal Cell Implants Improve Parkinson's
A team at Emory University School of Medicine has shown that
implanting retinal cells into the brains of people with advanced
Parkinson's disease can improve motor function by almost half,
according to a follow-up study of six patients. The team
noted: "We've been following these six participants for over a year,
and we've found they've improved, on average, nearly 50 per cent in
motor function." The retinal cells used were taken from deceased
donors and grown in the lab. The team is not using
immunosuppressants.


Reference
Result presented April 18 at the annual conference of the American
Academy of Neurology in Denver and reported in the New Scientist ,
April 18, 2002.

N.B: There are no clinical treatments for Parkinson's based on
cloning or embryonic stem cells.


In Animals
Stimulating Adult Brain Stem Cells Decreases Parkinson's Symptoms
Injection of growth protein into brains of Parkinson's rats caused
their neural stem cells to grow, migrate to the site of damage, and
begin to replace missing nerve cells. Eighty percent (80%) of the
rats received a benefit from the treatment, with no tumor formation.

Reference:
J. Fallon et al.; "In vivo induction of massive
proliferation,directed migration, and differentiation of neural cells
in the adult mammalian brain," Proc. Natl. Acad. Sci. USA 97, 14686-
14691; December 19, 2000.

Progenitor Cells Reverse Severe Parkinson's Symptoms in Rats
Researchers at Chicago's Rush University report coaxing progenitor
cells from the brains of rats into becoming dopamine neurons to treat
Parkinson's disease. Led by Paul Carvey, the team discovered an
important "shortcut" to creating a more efficient, more reliable, and
safer source of stem cells with the ability to turn into specific
neurons or brain cells. This study is the first to identify the
signal that instructs stem/progenitor cells to become dopamine
neurons. The researchers watched the cells develop, and selected and
grew cells that were close to becoming neurons. They then grafted the
cells into brains of Parkinson's rats, effectively curing the
animals' severe Parkinson symptoms. The ability to select and grow
large numbers of adult stem cells that would become neurons also has
the potential to revolutionize the treatment of Alzheimer's disease,
multiple sclerosis and numerous other diseases and disorders of the
brain and nervous system.

Reference:
Results reported at the Experimental Biology Meeting in New Orleans,
April 2002.

N.B. =97In contrast to these animal studies using adult stem cells, a
widely publicized study showed just over 50% of Parkinson's rats
injected with mouse embryonic stem cells receiving a modest benefit,
but one-fifth (20%) of the rats died of brain tumors caused by the
embryonic stem cells.

Reference:
L.M. Bjorklund et al.; "Embryonic stem cells develop into functional
dopaminergic neurons after transplantation in a Parkinson rat model,"
Proc. Natl. Acad. Sci. USA 99, 2344-2349; Feb 19, 2002 (published
online Jan 8, 2002)

Gene Therapies Treat Parkinson's in Rats, Monkeys
The injection of two corrective genes into a specific brain region
generated significant restoration of normal limb movement in rats
with Parkinson's disease. Limb impairments were completely reversed
in rats that had near-total Parkinsonian lesions on only one side of
the brain, meaning that some of their dopamine-producing cells
remained intact. But even in the rats with complete destruction of
dopamine-producing cells, the delivery of gene therapy resulted in a
limited amount of restored motor function. "We anticipate gene
therapy will offer a way to help patients with Parkinson's disease
live many years longer free of disabling symptoms," the researchers
noted.

Reference:
D. Kirik et al.; "Reversal of motor impairments in parkinsonian rats
by continuous intrastriatal delivery of L-dopa using rAAV-mediated
gene transfer," Proceedings of the National Academy of Sciences USA
99, 4708-4713; April 2, 2002.

A Japanese research team has demonstrated delayed delivery of gene
therapy can provide significant recovery from Parkinson's symptoms.
Four weeks after inducing Parkinson's damage in their brains, rats
were given an injection of a gene vector which produced a growth
protein call "glial cell line-derived neurotrophic factor" (GDNF).
The animals showed remarkably higher levels of dopamine secretion and
significant behavioral recovery, even up to 20 weeks following the
injection.

Reference:
L. Wang et al.; "Delayed delivery of AAV-GDNF prevents nigral
neurodegeneration and promotes functional recovery in a rat model of
Parkinson's disease," Gene Therapy 9, 381-389; March 2002.

Treatment with three gene therapy vectors has shown behavioral
recovery in Parkinson's monkeys. The treatment resulted in remarkable
improvement in manual dexterity and restoration of motor functions,
with the behavioral recovery persisting for over 10 months in one
case. The scientists say that this triple gene therapy method may
offer a potential therapeutic strategy for Parkinson's disease.

Reference:
S. Muramatsu et al.; "Behavioral recovery in a primate model of
Parkinson's disease by triple transduction of striatal cells with
adeno-associated viral vectors expressing dopamine-synthesizing
enzymes," Human Gene Therapy 13, 345-354; February 10, 2002.

Date: Mon, 06 Jan 2003 14:09:12 -0000
Subject: [StemCells] Clones bad choice for therapy
Here is an article that explains why clones are a bad choice for
therapy (it is not just my opinion).  We have to be careful in
allowing emotions override logic. As I have pointed out many times,
pretty much none of the success stores have used embryonic stem cells
(in the April 2001 JAMA article RE:hope for ALS patients it says, "A
series of investigations headed by Evan Snyder, MD, PhD, demonstrated
that neural stem cells - more mature than embryonic stem cells - zoom
to areas of brain damage caused by tumors and other injuries (Proc
Natl Acad Sci. 2000;97:12846-12851)."  Furthermore, there are problem
w/cloning that is inherent in the procedure that makes them unusable
for therapies, and the failure rate would require far too many
eggs/patient to achieve - resulting in the exploitation of poor women
in third world nations.  I have provided evidence that the process
would be far to expensive for treatment - and too lengthy, when you
consider diabetes had been 'cured' in mice w.im 40 days of an
injection of their own cells (you can search for the articles I've
placed here.  In particular, last June I put up a lot of stuff.  My
next post will be re:Alzheimers).  Remember, Dr. Gail Martin - the
lady who is credited for isolating Embryonic Stem Cells (ES) said
that in 20 years of working with them they have yet to cure one mouse
of a disease!

------------------------------------------------------
Clone Study Casts Doubt on Stem Cells
Variations in Mice Raise Human Research Issues

By Rick Weiss
Washington Post Staff Writer
Friday, July 6, 2001; Page A01

Mice cloned from embryonic stem cells may look identical, but many of
them actually differ from one another by harboring unique genetic
abnormalities, scientists have learned.

The presence of these subtle and previously undetected genetic
glitches could help explain why so many clones do not survive to
birth. It also adds credence to scientists' fears that even
apparently healthy clones are not as normal as they seem -- a
consideration relevant to the debate over the safety and morality of
human cloning.

The work also shows for the first time that embryonic stem cells --
which are at the center of an escalating political and ethical debate
as President Bush decides whether federal funds should be spent to
study them -- are surprisingly genetically unstable, at least in mice.

If the same is true for human embryonic stem cells, researchers said,
then scientists may face unexpected challenges as they try to turn
the controversial cells into treatments for various degenerative
conditions.

In an unusual move reflecting the politically sensitive nature of the
research, the scientists who conducted the study deleted at the last
minute part of a sentence in their published report that had alluded
to this potential ramification, and added a sentence emphasizing the
cells' therapeutic promise. It is true that genetic instability in
human embryonic stem cells may complicate efforts to turn the cells
into cures, the lead researcher said yesterday. But he said he was
afraid that any mention of that potential problem in the article
might be exaggerated by political factions that oppose the research
on religious and ethical grounds.

"A non-scientist could really misinterpret the words," said Rudolf
Jaenisch of the Whitehead Institute for Biomedical Research in
Cambridge, Mass., who led the research with Ryuzo Yanagimachi of the
University of Hawaii. "It does need to be checked to see if human
[embryonic stem] cells are also so unstable. But even if they are, we
don't think it will be a problem."

The new work, published in today's issue of the journal Science,
focused on cloned mice, each created from a single cell. But rather
than making the clones from a single adult skin cell, as is common in
the field, scientists made these from single embryonic stem cells, a
special kind of cell of interest to cloners because they produce live
clones at 10 times the efficiency of other kinds of cells.

Surprisingly, tests indicated that although every cloned mouse had
exactly the same genes as every other -- a hallmark of cloning --
they varied considerably from one to the next in terms of which of
their genes were active and which were dormant, a result of aberrant
gene regulation.

The apparently random variation in the way genes were regulated in
the clones suggests that the cloning process itself can sometimes
scramble the molecular "switches" inside cells that tell various
genes when to turn on and when to turn off. Considering what a
delicately orchestrated process fetal development is, such regulatory
mayhem in a developing clone could help explain why the vast majority
of cloned animals die long before they are born, and why live-born
clones often suffer from serious malformations.

Moreover, none of the abnormally regulated genes was predictive by
itself of whether a clone was healthy. That means it won't be easy to
come up with a genetic test to determine which developing clones will
be healthy -- a strike against some advocates of human cloning who
have claimed they could avoid creating genetically aberrant human
clones by testing developing fetuses and aborting those whose genes
seem abnormal.

To see if the genetic variation found in the mouse clones was
entirely a result of the cloning process or was in part "inherited"
from the originating stem cells, the team did molecular tests on
individual mouse embryonic stem cells. They found that even stem
cells that should have been identical displayed very different
patterns of gene activation, an indication that gene switches are
inherently unstable in this class of cells.

Such varying patterns could have big effects on how cells behave,
scientists said. Imagine that a score for a piece of music is
photocopied many times, but the notation saying which instruments
should actually play their parts is different from one copy to the
next -- the equivalent to some genes being on and others off. The
sequence of notes would be identical in each copy -- the scores would
be clones -- but each would sound very different when played.

If human embryonic stem cells prove to be as variable in this way as
their mouse counterparts apparently are, then a political compromise
floated by the Bush administration in the stem cell debate may not be
as practical as some had hoped. That possible compromise would limit
the number of embryonic stem cell lines, or colonies, that scientists
could work on, thus limiting the number of embryos destroyed. But if
seemingly identical cell lines are subtly different from each other,
then some may have particular promise for certain uses -- such as to
make new brain cells for Parkinson's patients -- and others may excel
at other tasks, such as becoming cardiac tissue for heart attack
patients.

"You may have to establish hundreds of lines to get the few you'd
want to have," said John Gearhart, a stem cell researcher at Johns
Hopkins University.

Gearhart said he agreed with Jaenisch that the newly discovered
genetic instability in embryonic stem cells will probably not
interfere with scientists' goal of turning the cells into therapies.
Proper "on-off" patterns of gene activity in stem cells are crucial
for the coordinated development of an entire fetus, he said, but are
less crucial if all that is wanted is to make the cells grow into
pure tissues, such as cardiac muscle.

In the original draft of their paper, the authors called for research
to see if genetic instability in stem cells might "limit their use in
clinical applications." A spokesman for Science said editors there
allowed Jaenisch to eliminate that language just days before
publication because the change did not involve scientific data, only
the authors' interpretation of their data.

Jaenisch said no one knows yet if so-called adult stem cells, which
are retrieved from adults instead of from embryos, are more
genetically stable than embryonic stem cells. Some opponents of
embryo research have advocated focusing solely on adult stem cells.

Date: Mon, 06 Jan 2003 14:09:12 -0000
Subject: [StemCells] Clones bad choice for therapy Here is an article that explains why clones are a bad choice for
therapy (it is not just my opinion).  We have to be careful in
allowing emotions override logic. As I have pointed out many times,
pretty much none of the success stores have used embryonic stem cells
(in the April 2001 JAMA article RE:hope for ALS patients it says, "A
series of investigations headed by Evan Snyder, MD, PhD, demonstrated
that neural stem cells - more mature than embryonic stem cells - zoom
to areas of brain damage caused by tumors and other injuries (Proc
Natl Acad Sci. 2000;97:12846-12851)."  Furthermore, there are problem
w/cloning that is inherent in the procedure that makes them unusable
for therapies, and the failure rate would require far too many
eggs/patient to achieve - resulting in the exploitation of poor women
in third world nations.  I have provided evidence that the process
would be far to expensive for treatment - and too lengthy, when you
consider diabetes had been 'cured' in mice w.im 40 days of an
injection of their own cells (you can search for the articles I've
placed here.  In particular, last June I put up a lot of stuff.  My
next post will be re:Alzheimers).  Remember, Dr. Gail Martin - the
lady who is credited for isolating Embryonic Stem Cells (ES) said
that in 20 years of working with them they have yet to cure one mouse
of a disease!

--------------------------------------------------------
Clone Study Casts Doubt on Stem Cells
Variations in Mice Raise Human Research Issues

By Rick Weiss
Washington Post Staff Writer
Friday, July 6, 2001; Page A01

Mice cloned from embryonic stem cells may look identical, but many of
them actually differ from one another by harboring unique genetic
abnormalities, scientists have learned.

The presence of these subtle and previously undetected genetic
glitches could help explain why so many clones do not survive to
birth. It also adds credence to scientists' fears that even
apparently healthy clones are not as normal as they seem -- a
consideration relevant to the debate over the safety and morality of
human cloning.

The work also shows for the first time that embryonic stem cells --
which are at the center of an escalating political and ethical debate
as President Bush decides whether federal funds should be spent to
study them -- are surprisingly genetically unstable, at least in mice.

If the same is true for human embryonic stem cells, researchers said,
then scientists may face unexpected challenges as they try to turn
the controversial cells into treatments for various degenerative
conditions.

In an unusual move reflecting the politically sensitive nature of the
research, the scientists who conducted the study deleted at the last
minute part of a sentence in their published report that had alluded
to this potential ramification, and added a sentence emphasizing the
cells' therapeutic promise. It is true that genetic instability in
human embryonic stem cells may complicate efforts to turn the cells
into cures, the lead researcher said yesterday. But he said he was
afraid that any mention of that potential problem in the article
might be exaggerated by political factions that oppose the research
on religious and ethical grounds.

"A non-scientist could really misinterpret the words," said Rudolf
Jaenisch of the Whitehead Institute for Biomedical Research in
Cambridge, Mass., who led the research with Ryuzo Yanagimachi of the
University of Hawaii. "It does need to be checked to see if human
[embryonic stem] cells are also so unstable. But even if they are, we
don't think it will be a problem."

The new work, published in today's issue of the journal Science,
focused on cloned mice, each created from a single cell. But rather
than making the clones from a single adult skin cell, as is common in
the field, scientists made these from single embryonic stem cells, a
special kind of cell of interest to cloners because they produce live
clones at 10 times the efficiency of other kinds of cells.

Surprisingly, tests indicated that although every cloned mouse had
exactly the same genes as every other -- a hallmark of cloning --
they varied considerably from one to the next in terms of which of
their genes were active and which were dormant, a result of aberrant
gene regulation.

The apparently random variation in the way genes were regulated in
the clones suggests that the cloning process itself can sometimes
scramble the molecular "switches" inside cells that tell various
genes when to turn on and when to turn off. Considering what a
delicately orchestrated process fetal development is, such regulatory
mayhem in a developing clone could help explain why the vast majority
of cloned animals die long before they are born, and why live-born
clones often suffer from serious malformations.

Moreover, none of the abnormally regulated genes was predictive by
itself of whether a clone was healthy. That means it won't be easy to
come up with a genetic test to determine which developing clones will
be healthy -- a strike against some advocates of human cloning who
have claimed they could avoid creating genetically aberrant human
clones by testing developing fetuses and aborting those whose genes
seem abnormal.

To see if the genetic variation found in the mouse clones was
entirely a result of the cloning process or was in part "inherited"
from the originating stem cells, the team did molecular tests on
individual mouse embryonic stem cells. They found that even stem
cells that should have been identical displayed very different
patterns of gene activation, an indication that gene switches are
inherently unstable in this class of cells.

Such varying patterns could have big effects on how cells behave,
scientists said. Imagine that a score for a piece of music is
photocopied many times, but the notation saying which instruments
should actually play their parts is different from one copy to the
next -- the equivalent to some genes being on and others off. The
sequence of notes would be identical in each copy -- the scores would
be clones -- but each would sound very different when played.

If human embryonic stem cells prove to be as variable in this way as
their mouse counterparts apparently are, then a political compromise
floated by the Bush administration in the stem cell debate may not be
as practical as some had hoped. That possible compromise would limit
the number of embryonic stem cell lines, or colonies, that scientists
could work on, thus limiting the number of embryos destroyed. But if
seemingly identical cell lines are subtly different from each other,
then some may have particular promise for certain uses -- such as to
make new brain cells for Parkinson's patients -- and others may excel
at other tasks, such as becoming cardiac tissue for heart attack
patients.

"You may have to establish hundreds of lines to get the few you'd
want to have," said John Gearhart, a stem cell researcher at Johns
Hopkins University.

Gearhart said he agreed with Jaenisch that the newly discovered
genetic instability in embryonic stem cells will probably not
interfere with scientists' goal of turning the cells into therapies.
Proper "on-off" patterns of gene activity in stem cells are crucial
for the coordinated development of an entire fetus, he said, but are
less crucial if all that is wanted is to make the cells grow into
pure tissues, such as cardiac muscle.

In the original draft of their paper, the authors called for research
to see if genetic instability in stem cells might "limit their use in
clinical applications." A spokesman for Science said editors there
allowed Jaenisch to eliminate that language just days before
publication because the change did not involve scientific data, only
the authors' interpretation of their data.

Jaenisch said no one knows yet if so-called adult stem cells, which
are retrieved from adults instead of from embryos, are more
genetically stable than embryonic stem cells. Some opponents of
embryo research have advocated focusing solely on adult stem cells.