Archive for November 2012

Let’s Review: Part Five

November 19, 2012

#15.  Dr. Mark Tuzynski talking about axons growing abundantly across the injury site in rats with cords transected two weeks post-injury.  He used human neural stem cells along with a gel matrix to get this result, and he’s right now trying to repeat the experiment with primates.  Such good work, so carefully done, so encouraging.

#16.  Getting an update from Dr. Hans Keirstead, who has taken “old” astrocyte cells from an SCI scar and turned back the clock — manipulated them into becoming “young” and therefore useful instead of prohibitive.

#17.  Hearing about a surgery that can restore some hand function (“You won’t be able to play a guitar, but you’ll be able to hold a pen . . . “) for quads.  Dr. Justin Brown is currently looking for patients.

#18.  Finally, can’t stop without mentioning the geek/toy room at RIRC.  So much creativity and effort and ingenuity going into trying to get tools made that will help people do the rehab that’s going to be a key component of any cure that comes from the labs.

Let’s Review: Part Four

November 17, 2012

#12.  Just being in the same room with the head of the California Institute of Regenerative Medicine (CIRM), which still has control of more than a billion dollars to spend on stem cell-based research, thanks to the voters and citizens of CA. 

#13.  Well, that has to be hearing Dr. Stephen Huhn of Stem Cells Inc describe clinical trials on SCI chronics, happening right now in Zurich.

#14.  Ah, so many things from the 2nd Dr. Jerry Silver talk.  One is the moderator, Matt Roderick, telling us that Dr. Silver convinced a researcher Matt knows to work on chronics.  The other is Dr. Silver’s new work showing that regeneration can happen even in chronics, even in complete transections.  Chronics, chronics, chronics.  

Let’s Review: Part Three

November 17, 2012

Moving right along . . . we’re on my ninth important takeaway from the conference.

#9.  Marilyn’s announcement that u2fp has recruited a team of top researchers to serve as their Scientific Advisory Board.  It’s pretty stunning, to think that this little organization, started 7 years ago with no money, no connections, nothing but grit and frustration with the status quo has stepped up in so many ways.  

#10.  Advocate Dennis Tesolat saying, “A hospital bed is a lonely place.”  Advocate Bob Yant saying that he went to the top 12 researchers in the world and asked each of them, “What have we done so far, what do we still need to do?”  And got a unanimous answer: regenerate the corticospinal tract, which is, incredibly, exactly what’s being described right here.  Advocate Roman Reed saying he thinks we have the winning lottery ticket right in this room.

#11.  Dr Steward saying that if there were $1 Billion, the Manhattan Project would happen.  Dr. Silver saying that his lab is working on chronics, and that he thinks everybody who has a robust result SHOULD be working on chronics.

Let’s Review: Part Two

November 15, 2012

Keeping with the Let’s Review numbering in order of appearance, here’s what stood out to me next:

#5.  At the Q and A session with Dr Blackmore and Dr Steward, advocate Bob Yant’s comment: 

I’ve been to maybe 100 conferences, and this moment is almost surreal, to have been in this room hearing two different scientists talk about regeneration in published work that led to functional recovery.

 #6. Ravi Bellamkonda’s clever and necessary delivery system for ChABC, the 50-100 nanometer microtube that lets the ChABC go after the CSPGs for as long as six weeks with a single application.

#7.  This isn’t in the blog anywhere, but there was a moment on the first day after Jerry Silver talked about removing the CSPG roadblocks when he told me that today was just the warm-up . . . he was going to talk about the really important new stuff on Friday.  The man is fairly humming with intensity and a sort of happy warrior feeling.

#8.  From the Q and A just before lunch on the first day, when Os Steward stood up and said that he’d been thinking about the concept of a Manhattan-style project . . . what would it take, really, to create a single-minded, worldwide collaboration intensely focused on repairing a damaged cord?  His answer was a billion dollars.  And our friend from Ireland, Martin Codyre, was quick to say that if it looked like there was a plan and an Oppenheimer to run it, the money would be there.  

More Review to come.

 

Let’s Review: Part One

November 15, 2012

I’m writing this from my desk at our house near Seattle . . . everyone who came to Working2Walk is by now long since home and settled back into whatever routines normally fill their days.  As I look over the posts on this blog, it occurs to me that there are a couple of things left to do.  One is to say thanks again to the people who worked all year to bring this thing into being, mostly as volunteers, one or two as very poorly compensated staff.  We owe them.

Another is to sift through all this information and highlight a few places that stand out for follow up and further review.  Your list might be different from mine on that score, and I’d be love to hear about it if that’s the case.  So, starting from the beginning . . .

1. Marilyn Smith’s words from her opening remarksWe have three tools. EDUCATE, ORGANIZE, and TAKE ACTION.  As those with the most skin in the game, we need to invest ourselves in the process.  The most powerful force we have going for us, though, is BELIEF.  We want you to leave this conference with belief in the power of science, knowledge, and advocacy.

2. Dr. Os Steward’s excitement about his CTRP team’s success in finding a specific gene — called PTEN — that blocks regeneration of nerves.  When someone with his reputation for calm and caution and meticulous communication shows enthusiasm, it’s definitely catching.  I’ve gone back and put some links into that post so you can read the background material yourself if you’re interested.

3. Dr. Murray Blackmore’s sheer cleverness, determination, and most especially, youth.  I’ve heard for a long time now that SCI research used to be considered a big fat dead end to any serious career.  “You’ll waste your life trying to solve that!  Focus on something that’s actually achievable!”  That was once common advice.  And here was this sharp new mind attacking the problems with impressive ingenuity and determination.  I especially liked the part where he said that he went data-mining in cancer research about transcription factors and quickly discovered that there are 210 of them that seem to have a role in cancer growth.  When he cross-checked that list of 210 with the 12 that he knew were involved with axon growth, 11 out of 12 were on the list.  As he told us, “That means the other 199 suddenly become very interesting . . . ”  In his talk, Blackmore described his just-published research that shows transcription factors can make old neurons think they’re young and still able to regenerate, so this matters.

4. Oy.  This is going to be a long list, I can see that.  I’ll put this up as part one and keep working on the rest.

At the RIRC Lab

November 3, 2012

Okay, this is basic stuff but until I just saw it, I didn’t really get it.

There’s a post-doc showing us preserved specimens of a human brain and spinal cord, a rat brain and cord, and a mouse brain and cord.

  • The human brain is like a medium sized cantaloupe.
  • The rat brain is like a fattish raspberry.
  • The mouse brain is like a medium sized peanut.
  • The mouse cord is a bit of thin spaghetti, about an inch and a half long.
  • The rat cord is worm thickness, maybe twice as long as the mouse cord.
  • The human cord looks like a tangly fat mess of variably thick strands . . . the center is the cord itself, still surrounded in dura, and there are these things like flaps that hold the dorsal root ganglia.  It’s as long as my forearm.  You can see why they call the caudal equina that — it does look like a horse’s tail.

I’m kind of freaked out, for two reasons.  One is just the idea that this thing in front of me used to be somebody’s central nervous system.  The other is that this makes it real, how big the problems are that come with trying to ramp up from what works in mice to what works in us.   The guy is saying that size isn’t everything, because physiologically there’s so much that’s the same between these species.

Here are the names of the other stations we can visit here:

fMRI, electron microscope, 3-D imaging, Histology, and two-photon microscope . . . not much time left!

Talking with Robert Gramer at the fMRI station.  Only 34% of injuries are complete, and most research has been done on completes, and what they know is that only 40% of normal activation is there.  The brain recruits available capacity for other things.

So, what happens with incompletes?  Specifically, do ASIA Ds have changed patterns of activation?  Yes, they actually use even more brain activation in the usual areas when using their legs.  They did a study of ASIA C and Ds who could walk more than 10 meters with assistance, and looked at ASIA impairment scale and gait velocity.   They used fMRI, sent patients on their backs into the doughnut and showed them a cartoon of a foot moving to tell them when to move their foot, which was sticking out.  These were chronics, injured 2 years to more than 20 years.

What they saw on their screens was that people with incomplete injuries were activating big sections of their brains that the AB controls didn’t need . . . even using the right side of the brain to move the right foot, which isn’t the normal pattern.  The motor planning area was lit up too, because incompletes have to use it a lot more than AB people do; it takes concentration for incompletes to do what is automated in non-injured brains.  The activation patterns got stronger over time — meaning that the longer-term chronics were using more of their brains than the shorter term ones.

Then they showed that faster gait correlates with higher activation of the part of the brain that has to do with concentration and high cognitive functioning.

Why does this matter?  Because the old studies that were based on completes meant that eventual therapies would need to address both brain inactivity and cord inactivity . . . but this one means that in the case of incompletes, it will be a one-step event, because the brain is already functioning even better than normal when it comes to movement.

Here’s the interesting thing.  All this was meant as a pretest.  It was followed by having the same subjects visualize themselves doing motor tasks, 30 minutes a day, 3 days a week, for 8 weeks, listening to headphones giving them vivid imagery of themselves doing tasks (picking up something with their toes e.g.), and compared to those who didn’t do visualization, their brains were more activated.

And that’s your brain geekout for the day.  Time for lunch, and then almost everybody is leaving.

It’s been fun, and challenging, and hopeful.

Inside Gross Hall

November 3, 2012

It’s not gross at all, so far.  🙂  One of the young post-docs is showing us how he designs equipment to test and train rats and monkeys.  The animals get trained before injury on this equipment, which lets them use a baseline to see whether or not treatments are working.  The device is called the autoGSN.

One of the things they want animals to be able to do is make a choice to grab a bar.  They need them to have volitional control because anything that isn’t coming from the animal can’t be trusted — it might be a result of something the investigator is doing.  They’re currently working with 22 rats, who got 3 weeks of training before their injuries.

(This is one of the things that’s hard to remember about the research process — how bloody much time and thought and effort has to go into figuring out how to get reliable, true measurements that mean what you hope they mean.)

Now showing a suspended gait thing that’s on a curved overhead track — the usual ones only go forward.  They need ways to measure trunk strength and stability . . . the idea is to translate standing trunk balance to sitting balance.  Kelly’s strapping an AB assistant into the harness so that she can show us how a Wii-style game works.  There’s a sky scene projected on the wall in front of her with a floating balloon in it.  Her job is to use her body (trunk muscles) to pop the balloon.  At this point they only do this with incompletes, mostly due to IRB issues (gov’t control of risk stuff) but have just submitted a protocol for permission to work with completes.

Their incomplete studies have been successful, meaning, they were safe. She did mental practice and gait training with incomplete sci and looked at brain active before and after task.

They showed that people with incomplete injuries had cortical changes in the brain after training.  Low level Asia Cs to Ds who are incomplete can have rehab patterns set to take advantage of the parts of their brains that MRIs show are helping them.

Another area of focus is motivation.  Music, gaming, etc., are areas they’re working on as ways to get people to do the tedious and repetitive work that constitutes training.

Robotrunk is another thing they have in development . . . they want reliable and valid tools that can go quickly into the clinic.  What matters here is two things — one is reliable measuring tools so that treatments can be shown to be effective.  The other is to make devices that can become home-based rehab tools that are cheap and simple to use.

Guy is showing a brain interface system (not cheap, simple or home-based for sure!) . . . they’ve succeeded in wiring an AB person, asking that person to imagine walking as they look at an avatar on a computer screen, and seeing the avatar walk.  New paper published showing the success of this. The idea is to (eventually) use brain signals to activate (internal) prosthetics so that people with injuries can walk just by imagining that they are.

The music glove . . . it’s kind of like Guitar Hero, if you’ve ever seen that.  The subject wears a wired glove on one hand while music plays on an attached laptop.  Right now there’s an AB young man (who turned out to be Dr. Steward’s grandson) operating the thing to the sound of I Heard It Through the Grapevine.  He has to touch thumb to finger in time with the beat, and on the screen there are icons like little guitars floating up a fret board that show which finger to tap when . . . the idea is to motivate users to do their OT by making it challenging and game-like – more or less the same principle that gets AB people into the gym for aerobics classes . . . hit the beat, follow the instructions. More fun than doing reps with a set of weights.

And, another machine that works in a similar way, except that it has a ramp-up function for people with minimal ability to move their fingers.  At first it will do all the work for the hand, and then gradually – very gradually – back off as the fingers are able to work on their own.

And, another one — (people, this is like being a super-amazing toyland) – this time a small highly wired and sensitive package that sits on the subject’s back like a papoose. It’s attached to a computer that shows in realtime how successfully the person is using their trunk muscles. It knows if you’re not sitting up straight, and it knows if you’re not trying hard, and it knows exactly which muscles you’re pushing with, and god knows what other stuff. Seems like a highly useful tool to me.

Okay, half my roam-around time is gone already, and I haven’t even been in any of the basic science labs. 😦 Hate to leave this building!