Live from Working 2 Walk 2011!

[Isildur]

To walk again? I would do it even 7/7/7. Recovery worth all the effort.

The application in the fda is a solid state, surgically implanted scaffold. We anticipate within the next several months submitting an injectible drug-releasing version of this scaffold. The scaffold alone has been shown to reduce the cavity all by itself. And the surrounding tissue gets subjected to lots of stresses, so it's possible that there's just a

Kate, what is the end of that paragraph?

Thanks for your time and hard work

[Christopher Paddon]

yeah I would do 7/7/7 too but I was thinking of a practical regime in an institution

[Christopher Paddon]

why is everything over 5 years away? - the only time frame mentioned is 8 years I think

[nrf]

Who wouldn't do 4,4,4 if it was with the goal of walking again - 6 days a week seems a little extreme, how would you get staff to come in in the weekend?

We would be delighted to work Saturday's. If we could get our medical system to be less rigid it would be easy. Physiologists(personal trainers) will work for half the pay of a PT and are delighted to get paid to get cardio and strength training all at once. The first week or two wears them out so we rotate left for three minutes, right for three minutes then hips for three minutes. Our PT is a great guy and enjoys jumping in even though he's fifty, he went to a treadmill training class at TIRR with the Neuro Recovery Network. Two of our trainers went to Project Walk to attend their train your trainer school and learned a great deal about methods that are invaluable.

[Christopher Paddon]

Well, in my case, a cure is needed before any of that would be any use as I have a complete injury, so it's academic at this stage.

[nrf]

christopher paddon,

my son is a 17 year old with a c5/6 asia a complete post over 3 years. he's not walking but is beginning after 2 years of treadmill training to get trunk control and much improved breathing and stamina. his overall health improves as time goes by. When stem cells are ready he will be ready, if stem cells are never ready he is healthier due to the movement.I see it as a win win.

[betheny]

Awww, Sue and Colin at 25 years! Congratulate them for me, pls, Kate!

I'm so not into seminars, but it all sounds really good and I wish I could see Marilyn, Sue, Colin, Donna, and of course my beloved bleeding heart intellectual-Kate! Tell Paolo I'm proud he made it, I know it's a struggle.

I back you all, and I'm v. proud of what you've done. I know what's involved, it's blood and guts determination, bullheaded stubbornness, keeping your eye on the ball and 300 balls in the air. Way to kick ass, my former compadres!

[Christopher Paddon]

Do you do the treadmill training at home?

[Scaper1]

A big thank you to Kate and all of the W2W organizers, presenters, and attendees. Some really promising stuff there, I hope they can move on it quickly. It's extremely frustrating that the bureaucracy of clinical trials seems to trump the urgency to get them going.

[Schmeky]

Kate,

Thanks for all your hard work and effort. It is appreciated. What I have not really picked up on is any type of concrete time frame to take something to trial for chronics. But this doesn't surprise me.

Perhaps this will surface during the seminar.

[beachlover]

Thanks Kate for keeping us informed. I've followed the progress/this site since my oldest was with a classmate who dove into a pool and sustained a C5 injury... jeepers... 7 years a go. You and everyone are doing a great job. I'm happy to write checks when I can. Your posts help me direct my small checks to the groups/projects that I think could restore function for him and all who have sustained injury. Again, many thanks. You rock.

[arcy]

Interesting information and participations. I want to thank everybody again and Paolo too to gave voice to the thoughs of many sci people. I also agree with Scaper1 about bureaucracy..... another big problem.....

[Leif]

Kate,

Thanks for all your hard work and effort. It is appreciated. What I have not really picked up on is any type of concrete time frame to take something to trial for chronics. But this doesn't surprise me.

Perhaps this will surface during the seminar.

Hi David, maybe Kates post #24 addresses some of this

Great blogging Kate!

[Schmeky]

Leif,

Kate's post #17 is the one that caught my attention. I agree in part the problem is a component of engineering, combined with cell transplatation.

These guys (Invivo) make more sense, and "seem" to have a much more real approach, than anything I have read.

I have been looking for someone to support for real results and these guys look good, at least presently.

[kate]

Anthony Caggiano: Chondroitinase Overview

Good morning, sports fans ~

Marilyn's about to go to the microphone for announcements, then we'll get to Anthony Caggiano, who's the VP of pre-clinical development at Acorda Therapeutics.

Here she is: Today's gonna be another very busy day, so we need to get started on time and stay that way . . . yesterday was sort of a head-spinner. For those who might not feel like you remembered everything you heard, keep in mind there will be video up at u2fp just as soon as we can get it edited and online.

Also, there's that blog thang.

Raffling a video camera and an iTouch, get yer tickets! It's one of the ways we get cash to fund this conference and keep it affordable. There's a survey in your packet, which we always use to tweak this event, so please fill it out & be candid. This needs to be for you.

Tonight there's a reception at Kennedy Kreiger, and we arranged transportation over there . . . still have a little room. Buses leave at 5:45, return at 9:15, dinner provided. About 70 of you are already signed up & we still have room.

Donna's coming up to do the intro for Dr. Caggiano. He's here representing one of the few biotech companies working on chronic sci. Hundreds of studies have been published about chrondroitinase (hereafter called Chase).

Caggiano:
I'm the only person in the room with a tie on!

For those not familiar with Acorda, we were founded with the mission to develop therapies for sci. We made dalfampridine and ran clinical trials for sci and made it into phase 2 with them, but didn't get the results we had hoped for. We also tried it with ms, and those trials did succeed.

Right now there are 3 active development programs for sci, which I'll talk about a little, but I was asked specifically to talk about Chase. Most of what I'm going to do is talk about what other people are doing with this enzyme . . . that's because it's a big strength of this enzyme that everybody has done so much work with it. It's well understood.

Historically, the work goes back 20 years; Chase is correlated with expression of inhibitory molecules on reactive astrocytes, and with functional improvements.

Slide up about a paper Davies published back in 1999 about robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord. Soon after that (2001) another paper in Nature Neuroscience, and a year later one in Nature by Liz Bradbury at Kings College showing that Chase ABC promotes functional recovery after sci. She had rats crossing ladders. The functional improvement was out of proportion to the regeneration, which seemed to mean that other things were happening -- that Chase was affecting some other factors that had been preventing recovery. At the same time, Pizzorusso published Reactivation of Ocular Dominance Plasticity in the Adult Visual Cortex . . . this paper was important because it showed that things could be improved long after injury.

At Acorda, they showed that Chase could improve locomotion and bladder function after contusion injury in the rat spinal cord, published this in Journal of Neurotrauma in 2005.

Skipping to 2011, one scientist has shown that Chase combined with rehab promotes recovery of forlimb function in rats with chronic sci. This was a c4 dorsal cut injury; at 1 month post, the rats got the drug.

Chase delivered after a t10 hemisection in cats improved motor function. This paper was published in experimental neurology in 2008 by Nicole Tester an Dena Howland. However,rats are one level of difficulty and cats are orders of magnitude more complex.

So they did work with cats, and got the same kind of promising results.

What all this means is

There's clear evidence that Chase alters capacity for regeneration and plasticity
There's strong scientific rationale for Chase promotion of plasticity, sprouting and regeneration
There's evidence that Chase promotes functional recovery in lots of injury models
There's evidence that it works in multiple species: rats and cats
There's evidence from multiple independent labs that it works

So what's the hold up?

Colleagues have reported numerous negative studies --
Using Chase is a challenge, partly because delivery remains an issue --
There is as yet no safety record.

What has slowed the progress into human studies is . . .

From Liz Bradbury's work: if you put Chase at c5 into a rat cord, the distribution into the cord isn't very impressive . . rat cords are 9 cm, which is less than a third of the human cord. The area of a section of rat cord is 12.5 square mm, compared to about 100 for humans. So if Chase only spreads for 3 to 5 mm, how do you get greater distribution in humans? How many segments would you need to get results?

Slides showing visually the differences between the cross section of the human cord and the rat cord. Chase works when it gets to the gray matter in the center. It's a lot further to get there in humans than in rats.

Acorda now has 3 active programs in sci, for acute, subacute, and chronic (the chronic one is Chase)

Next steps: Find out if distribution (getting to the gray matter) is possible in pigs; this is being tried right now with a contract organization, using direct injections and intrathecal infusions.

Explore feasibility of direct injection, is it safe, will surgeons do it . . .

Find alternative means of delivery, using matrices or viral vectors; this is happening at Liz Bradbury's lab; it's working quite well but it's not clear how to "turn it off" . . .

What other methods are there to manipulate these enzymes?

They're looking a manipulating chase so that it stays stable at 37 centigrade, which is human body temperature.

Yikes, that was fast for 8:30 am . . .