ChinaSCINet Update

[Cspine]

I'm curious about hand and arm function as well. Walking is actually fairly low on my priority list. I have a little movement in my fingers and especially my thumbs, but it's more novel and not functional.

[LoryLù]

I just wanted to comment, that I really appreciate this dialogue. It is very helpful, informative and does provide context to our problem. As a passive viewer, I value this discussion and wish many therapies could be discussed in this manner (without any personal attacks). Thanks to all for their contributions.

[Wise Young]

Can you discuss preliminary outcomes in arm motor/ sensory improvement from this trial from the cervical subjects?

Since the study seems to be safe in C5 subjects and below, will C4 or higher be considered for phase 3? Or does another phase 1 and 2 study need to be done to assess the safety of this procedure with C4 and higher?

Thanks!

We are planning a phase II trial on high cervical injuries (C1-C4) to assess a different protocol where the cells are injected into the injury site and below in the injury site, rather than above and below the injury site. The reason why we restricted the current trial to C5 is because a C4 injury would require the that the upper (above the injury) injection be done at C3.

We have not analyzed the data for recovery of the hand and arm function yet and so I don't know the results yet.

Wise.

[Moe]

We are planning a phase II trial on high cervical injuries (C1-C4) to assess a different protocol where the cells are injected into the injury site and below in the injury site, rather than above and below the injury site. The reason why we restricted the current trial to C5 is because a C4 injury would require the that the upper (above the injury) injection be done at C3.

Wise.

I'm glad to learn that things are planned to move forward even for upper injuries. A read one of your posts regarding the safety for nerve fiber growth downwards and upwards for the c5 level… I’m glad that it has been proving good results on the safety data so far but my question to you is should we consider a much obvious higher risk for the c1-c2 level due to the location is much closer than a c5 to the brain? I’m curious and worried if somewhere up in the spinal cord there’s some kind of natural barrier preventing anything growing up in the skull… I understand that perhaps it’s too early to know but I’m curious of your point of view.

I thank you very much for your hard work and appreciate the time you share with us!

Cheers,

Moe

[ay2012]

So.... For those of us seeking any new kind of information, is there anything on the horizon we should check back here in a couple months for? I.e. update on the publishing process, organization or fundraising for the Phase III (in China and the US)? Thanks again.

[Wise Young]

I'm glad to learn that things are planned to move forward even for upper injuries. A read one of your posts regarding the safety for nerve fiber growth downwards and upwards for the c5 level… I’m glad that it has been proving good results on the safety data so far but my question to you is should we consider a much obvious higher risk for the c1-c2 level due to the location is much closer than a c5 to the brain? I’m curious and worried if somewhere up in the spinal cord there’s some kind of natural barrier preventing anything growing up in the skull… I understand that perhaps it’s too early to know but I’m curious of your point of view.

I thank you very much for your hard work and appreciate the time you share with us!

Cheers,

Moe

Moe, I don't think that there is a "natural barrier preventing anything growing up in the skull." The main reason why we have been reluctant to inject cells into the upper cervical spinal cord is that the phrenic nucleus (responsible for breathing) is located there (C2-C4). I think that surgeons would be willing to accept the risk of injecting cells into the injury site (since that has already been damaged). Injecting into non-traumatized C3 spinal cord is risk that most neurosurgeons are not willing to take.

Wise.

[Scaper1]

When is the upper injury trial scheduled? Will it be in China?

[Wise Young]

So.... For those of us seeking any new kind of information, is there anything on the horizon we should check back here in a couple months for? I.e. update on the publishing process, organization or fundraising for the Phase III (in China and the US)? Thanks again.

ay2012, I am sorry to sound repetitive but I simply have not yet decided when and how to present further data from the phase II study.

Our goal is to provide information for the community concerning the progress of the trials but not at the risk of jeopardizing publication or drawing criticism to the trial. We have already seen some examples of the latter here. In general, it is all right to present unpublished results at scientific meetings for discussion but it is not acceptable to present detailed data or analyses on internet. Some journals may consider this to be prepublication. So, we have to be careful.

On the other hand, one of the purposes of CareCure is to improve the community's understanding of the science and clinical trials that are going on. When I see gross misunderstandings of not only clinical trials but mechanisms of therapy and recovery, I feel that it is worthwhile discussing some of our observations if it helps people understand the science and spinal cord injury better.

We are of course working very hard to collect all the data, completing and sending the manuscripts for publication. In addition, of course, we will be submitting IND's (applications for clinical trials) to regulatory agencies around the world. We may have changes of the protocol. In March, we are planning to have investigator's workshops in China, India, Norway, and the U.S. All these may be associated with information that we may release here. So, stay tuned.

Wise.

[Wise Young]

When is the upper injury trial scheduled? Will it be in China?

I think that we will do it in the U.S. I am not sure when. Wise.

[Leif]

Moe,

be nicer!

you can experess your desagreement with what I post, but you can also ignore what I post.

Paolo

I would strongly support to not be posting the China data on CC until it is published in a journal. By that one will avoid the constant negative whining from non-productive people like Paolo.

[muskie]

Hey Doc, do you ever sleep? or do you have a 5 hour energy drink addiction? Seriously, thanks for the dedication.

[paolocipolla]

Paolo,

I am not sure where you get your information concerning scaffolding but I don't find much credible data supporting their use for repairing spinal cord injury in clinical trials for the following reasons:

1. There is no easy way of putting scaffolding inside a contused spinal cord without damaging the cord further. Most of the studies that I know have used transected spinal cords and placed the scaffold between two cut ends of the spinal cord. As you know, transected spinal cords are exceedingly rare.
2. Regeneration of axons through a scaffold faces two difficult obstacles. The first is to get the axons to grow into the scaffold. As Xu Xia-ming showed, this can be done by filling the scaffold with Schwann cells. The next obstacle is to get the axons to grow out of the scaffold into the surrounding cord. A few treatments (such as combination neurotrophins) seem to do this but the results have been modest, at best.
3. Some investigators have proposed that the spinal cord can be transected and the scaffold be put between the cut ends. I am not convinced that this is better than injecting cells into the spinal cord surrounding the injury site. The cells migrate into the injury site and form a continuous living bridge across the injury site.

So, perhaps you can tell us where you have gotten the impression that scaffolding is so promising. What studies are you referring to?

Wise.

Wise,

about point 1, you have posted many times about doing a mielotomy (which you say it improves outcomes) which require cutting the spinal cord.
How do you do that without causing more damage and more scarring?
I think the same procedure might be used to insert a solid scaffold in the spinal cord, does that make sense?
BTW you suggested me this solution using solid scaffolds last time we met in Italy.

About point 2 would you have a look to this study?
http://pubs.acs.org/action/doSearch?...ation=40025957

It seems that axons have crossed the scaffold and functional recovery has been seen and documented by electrophisiology.
While I agree that it is not something ready for clinical trials tomorrow (but maybe sooner than Cethrin and Muse cells) I would look into it (if you haven't yet) also because it is something done on animals one month after SCI, which should be close to chronic, while Cethrin and Muse cells have been tested just on acute that I know.

About your point 3, what about people with a very severe SCI if not anatomically complete SCI, how do you bridge the gap in these people? Maybe a solid scaffold could help? Or a peripheral nerve bridge may work better?

One more question, InVivo is investing a lot in biomaterials and planning clinical trials, do you thing it is built just around "hot air"? .. and you know I am not super excited about InVivo, but I would think they should have something.

Paolo

[Wise Young]

I would strongly support to not be posting the China data on CC until it is published in a journal. By that one will avoid the constant negative whining from non-productive people like Paolo.

Leif, thanks very much for the advice. I appreciate it and agree. Wise.

[Wise Young]

Hey Doc, do you ever sleep? or do you have a 5 hour energy drink addiction? Seriously, thanks for the dedication.

I post late either from jet lag or from being on the other side of the world. But seriously, I frequently stay up late because I am skyping with my colleagues concerning the clinical trials. A myriad decisions are associated with clinical trials. I am thankful for Boeing 777's and Skype. They allow me to fly directly to China from Newark and to communicate with my staff in Hong Kong in real time. Without these two developments, I think that ChinaSCINet would not have been possible. To avoid criticism, I disclose that I have no stock and have received no consulting fees from United or Microsoft, the owners respectively of the Boeing 777's and Skye. Wise.

[swh2007]

I post late either from jet lag or from being on the other side of the world. But seriously, I frequently stay up late because I am skyping with my colleagues concerning the clinical trials. A myriad decisions are associated with clinical trials. I am thankful for Boeing 777's and Skype. They allow me to fly directly to China from Newark and to communicate with my staff in Hong Kong in real time. Without these two developments, I think that ChinaSCINet would not have been possible. To avoid criticism, I disclose that I have no stock and have received no consulting fees from United or Microsoft, the owners respectively of the Boeing 777's and Skye. Wise.

My advice is to pay attention to the many who appreciate what you are doing and to ignore those few who criticize. Nobody ever did anything great without a few critical people following along. Happy Holidays!