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Breakout Session 4: Dr. Davies and Dr. Simon Archibald

Posted by katewillette on April 13, 2008

The name of the talk is Decorin and GRP-derived astrocytes.  The video Bruce made of his talk last year is on youtube, for those who want to see part A.  I’ll go find a link if I can before I post this.  This is it:

The glial scar is a physical and molecular barrier to axon growth — a fact that’s been known for a long time.  There’s an image up from a 1999 article in the Journal of Neuroscience that shows the green lines of axons straggling toward this thing that looks like a joint in a knee, where they stop dead. It’s the injury site.

His lab has been after 2 strategies:

Overcome scar and inhibitors to promote axon regeneration/plasticity.

Replace lost glia to bridge axon growth across the injury site.

What’s the right cell type for a bridge?

Non-CNS cell types (Schwann, engineered fibroblasts, olfactory ensheathing cells, macrophages, esc’s, marrow stromal cells) plus CNS cells, and 70% of adult CNS cells are astrocytes . . . but there are different kinds. Can we make the right kind?

Embryonic Stem Cells give rise to neuron prestricted precursors and glial restricted precursors (GRPs).  GRP’s can make either GDA Bmp or GDA gp130’s

The BMP’s have low inhibitor levels, they’re high in growth factors, and highly supportive of axon growth.  The gp130’s are the exact opposite.

So, where do you get grp cells?  From esc’s, unless you can genetically engineer the adult stem cell . . .a process that is not done yet.

So when you transplant the gdabmp’s what happens?  A ton of cells migrate into the margin of the injury and they align themselves very neatly — the opposite of what happens normally, where cells are all mixed up and helter skelter. They actually measured the misalignment between axons as about 59 degrees without the astrocyte gdabmp and 11 degrees with it.

These are the same slides we saw last year, and they still knock me out. All this was published in the Journal of Biology last year, after Dr. Davies was good enough to share it with us.  So what about functional recovery? The rats that got the good astrocytes are at almost full recovery — and the ones that got the bad ones get nada.

Neuropathic Pain . . . (sometimes called allodynia) can be made WORSE by implanting “naive” neural stem cells.  They turned into grp’s, then the bad kind of astrocytes, and pain was the result.  So they tested gdabmp, gdagp130, and grp’s — the rats that got the bmp’s were like normal rats, but the others were in serious pain–so serious that they had to stop the experiment ahead of time.

This is a major reason for people to hold off on the idea of getting any kind of undifferentiated stem cell injection to get recovery.  It’s not unlikely that the result will be more neuropathic pain.

Bottom line: the bmp astrocytes are all gain and no pain. I like that combination.

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Breakout Session 3: Hans Keirstead

Posted by katewillette on April 13, 2008

He says that in his lab they focus on acute, sub-acute, and chronic.  (Hans Keirstead, for those who haven’t met him, is kind of Robert Redford type.  I’m just sayin’.)  He’s describing an animal whose cord had been cut exactly 50%; within days it has lost a lot of tissue because of a “bad guy” molecule.  A single injection — of a restorative molecule –that could be given by any nurse — gets rid of a lot of the secondary degeneration.

There’s a video taken from underneath a glass table top on which a rat is dragging itself along — a single dose of the molecule prevents a LOT of the secondary damage.

The technology to do this is in clinical testing –Medarex began  clinical trials in 2006 for ulcerative colitis . . . the Keirstead approach is to find other (more profitable) diseases that studies can get funded for, then piggyback onto what’s learned and done in the process to bring the therapies to sci.

If Hans can get 1.5 million dollars, Medarex might provide him with $3 million worth of product to run a trial of his own

Subacutes— different beast completely from the acute.  Wow, he puts up a picture of a human egg sitting in a fallopian with a tiny blue speck of sperm heading its way. Wow.

We’re going to talk about how to grow human embryonic stem cell lines just for clinical use. The job is to be able to do that with certainty that they’re pure, and then be able to grow them into whatever you wanted.  Aborted fetuses are not a source for this for ethical, political, and practical reasons.

What if we had limitless sources of something like human heart tissue,not to grow new hearts, but to try out things that might

2 guys and a rat show up at the FDA and say, we’ve made a rat walk again . . . the FDA says, so what.  Do it again, under our regulations.

OEG’s are the cells that make myelin, the conductor that makes transmission of information through the cord possible.

He cooked up a soup to make pure OEG’s . . . it’s cooking time is 42 days.  They did this by simulating the media in which our own brains create these things.  This is the only place in the world where a pure and inexhaustible source of any kind of cell has been developed.

Hans just radiates confidence.

Geron is going to submit their IND to the feds this summer and they plan to go to clinical trial right away.  They went to the FDA and said they’d treated thoracic injuries in rats and the FDA said, well you can’t test humans with cervical injuries until you repeat the work with cervical injuries.  Jeebus.

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