ChinaSCINet Update

[Imight]

Let me clarify. The BW photo is just a methods photo illustrating the stages of training and the Kunming Locomotor Score (KLS), using several different patients. They have treated hundreds of patients in Kunming with the intradural decompression followed by intensive locomotor training. Close to 50% of those patients reach KLS V.

We started the clinical trial of chronic SCI with them last fall and they transplanted 20 ASIA A chronic SCI subjects with escalating doses of umbilical cord blood mononuclear cell transplants, then the cell transplants with methylprednisolone, and then the cell transplants plus methylprednisolone plus a 6 week course of lithium. We don't have 6 month followup data from the last two groups yet. That is why I am urging people to be patient.

I don't think that there is enough data to conclude that intensive locomotor training alone does or does not do anything for people who are chronic ASIA A SCI. I pointed out that Anton Wernig has already shown that nearly 75% of those are incomplete after injury will benefit from treadmill training. Presumably you belong to that category of people with incomplete injury.

Wise.

Ah ok got you, I thought you were showing us an actual persons recovery, ASIA A, chronic, KLS plus cell transplant. Got a bit excited there, because if he recovered THAT much in 6 months, that's simply amazing. Since he 'could' be acute, that's not so amazing, because people like Kevin Everett did actually recover that much in such a short period of time.

For a second I thought I just needed 6:6:6 (or possibly half the time, since I'm already at level 5) to gain all of that quickly.

KLS is inconclusive imo. It's still blind. but regardless, I think maximizing the initial 6 month therapy is extremely beneficial and important. I did some very intensive therapy to get to where I am but I was lucky (much like NFL Kevin Everett) and had the available resources. So many people I went to therapy with didn't have nearly the amount of therapy I had the first 6 months while the swelling was going down, they may have been able to recover a lot more. This was actually a common topic in the SCI support group.

[Oocofficial]

What is the basis for the comments that you have a severed spinal cord? Did they see this at surgery or was this something from an MRI?

Wise.

Hi Dr Young

That was the original diagnosis from the original MRI. But obviously it was a mis-diagnosis due to the recovery that I've had. . I'm thinking that there was a lot of blood which may have obscured the MRI.

James

[paolocipolla]

1.hongkong trial is fund by Hongkongnese,one condition is Hongkong residents only. This limitation has made the clinical trial less efficent than it could be. If it could have been removed more patient & more quicly would have joined the trial. Wouldn't that be better?
Wasn't really possible to find a way to accept patients from outside HK? For example what if a non profit org would cover the costs of patients coming from outside HK?
Well,by the way,Beijing has stem cell center welcomes other country patients.if u want to go,I can send information to u.
3.It is not allowed to take deposit for join a clinic trial. IMO this rule should be recosidered &/or a mechanism to motivate patients not to drop of the trial should be worked out to make the clinical trial effort more productive.
4.Well,again,Beijing Wujing hospital had been claimed cured sci for a few years,but the data only in that hospital.

It is great that 8 patient have been done in Hong Kong, but if 20 would have been done it would have been better, and possibly in less time.
We can't be happy with 8 patients in two years for a clincal trial center IMO.

Paolo

[Wise Young]

Ah ok got you, I thought you were showing us an actual persons recovery, ASIA A, chronic, KLS plus cell transplant. Got a bit excited there, because if he recovered THAT much in 6 months, that's simply amazing. Since he 'could' be acute, that's not so amazing, because people like Kevin Everett did actually recover that much in such a short period of time.

For a second I thought I just needed 6:6:6 (or possibly half the time, since I'm already at level 5) to gain all of that quickly.

KLS is inconclusive imo. It's still blind. but regardless, I think maximizing the initial 6 month therapy is extremely beneficial and important. I did some very intensive therapy to get to where I am but I was lucky (much like NFL Kevin Everett) and had the available resources. So many people I went to therapy with didn't have nearly the amount of therapy I had the first 6 months while the swelling was going down, they may have been able to recover a lot more. This was actually a common topic in the SCI support group.

Imight,

There are of course some patients in Kunming that recovered more than KLS V. In their original study of 30 patients that received the intradural decompression and then the intensive locomotor training, I remember about 5 patients that actually got to KLS IX. These are all ASIA A patients. The question is whether this was due to the subdural decompression. The surgery was done at 2 days to 30 days after injury and about half of the patients recovered more than expected in the following 3 months.

Dr. Zhu Hui is no longer with the Army General Hospital in Kunming. She retired from the Army and has moved to a private hospital and has set up both a neurosurgical and rehabilitation program there. As soon as I get detailed information about this place, I can post contact information. At the present, she doesn't have many English speakers on staff. The Army Hospital was not able to take foreign patients but now she not only can but wants to have foreign patients.

Wise.

[kz]

Hi Dr. Young ,
Thanks indeed for everything you do . I have a question regarding CETHRIN. you said that you plan to do clinical trial with cethrin sometimes in 2014 , and my understanding is cethrin was not tried on chronic asia A animals yet , and you have to do chronic asia A rats first before you do the human clinical trial (please correct me if i am wrong) , so , based on that, isn't a good idea that right now , you try to do clinical trial on DOGS THAT ARE ALREADT PARALYSED FROM SPINAL CORD INJURY (injury from car accidents , falls , etc , and assuming their owners agree to give it a try to see if it helps their dogs , and i am assuming that safety of cethrin is already is established in acute trials before) ?
wouldn't that save a lot of time and resources and we will know if it really works on animals with chronic SCI asia A or not before we do human trials? this way , those doge may get chance to get better(assuming it will works on chronics ASIA A) , and their injury is natural and close to human injury . it probably cost less because you do not have to creat the injury , wait to become chronics , and the owners might take care of their doges and probably the rehabilitation after the trial. and hopefully those doges get a chance to get better . JUst a thought , what do you think ? thanks so much.

[jsilver]

Hi Dr. Young ,
Thanks indeed for everything you do . I have a question regarding CETHRIN. you said that you plan to do clinical trial with cethrin sometimes in 2014 , and my understanding is cethrin was not tried on chronic asia A animals yet , and you have to do chronic asia A rats first before you do the human clinical trial (please correct me if i am wrong) , so , based on that, isn't a good idea that right now , you try to do clinical trial on DOGS THAT ARE ALREADT PARALYSED FROM SPINAL CORD INJURY (injury from car accidents , falls , etc , and assuming their owners agree to give it a try to see if it helps their dogs , and i am assuming that safety of cethrin is already is established in acute trials before) ?
wouldn't that save a lot of time and resources and we will know if it really works on animals with chronic SCI asia A or not before we do human trials? this way , those doge may get chance to get better(assuming it will works on chronics ASIA A) , and their injury is natural and close to human injury . it probably cost less because you do not have to creat the injury , wait to become chronics , and the owners might take care of their doges and probably the rehabilitation after the trial. and hopefully those doges get a chance to get better . JUst a thought , what do you think ? thanks so much.

This is a perfect question that needs an answer. However, a rodent experiment would be fine to start and straightforward to do. There is no data at present that Cethrin can work at chronic stages after SCI. We still really don't understand the basic biology of which cells Cethrin acts upon at acute stages. How anyone can even begin to propose a clinical trial without appropriate and easily doable animal experiments is baffling to me.

[KofQ]

How anyone can even begin to propose a clinical trial without appropriate and easily doable animal experiments is baffling to me.

Don't be baffled. I don't think anyone is proposing that at all.

No, we are planning to test Cethrin in chronic spinal cord injury. We will be studying it in animals as soon as a source becomes available...
...I remind you that I was talking about candidates for the next generation of therapies that we are planning to take to trial in 2014 or later. We are currently in the middle of 2012. I have said repeatedly here and in our Open Houses that much work will be needed to develop these therapies for trials. We are working closely with and helping Lisa McKerracher and Mari Dezawa to develop these therapies so that the cells can be tested in animals

[jsilver]

Don't be baffled. I don't think anyone is proposing that at all.

Right, then can we all agree that it is inappropriate to strongly predict when a human clinical trial might begin even BEFORE the data (even preliminary data) is in showing efficacy in an appropriate animal model?

I see nothing wrong with being cautious in our evaluations of what might or might not work in chronic SCI so as not to engender false hope. I would like to point out yet again that chronic SCI is a very special situation and one cannot and should not extrapolate that what works at acute stages will necessarily work at chronic stages.

I also see nothing wrong with Paolo's statement:


"Thanks Wise, that is what I suspected. So first you have to do the animal studies on chronic SCI (which will take at best a year, but mybe 2 or 3), then JUST IF it works animals with chronic SCI you can start clinical trials with cethrin on people with chronic SCI.
I think these are very relavant details you should have included in your presentation at the last open house."

Paolo

[Jim]

Jerry, don't you have anything better to do than come here and nitpick every sentence Wise writes? Why do you feel the need to try and discredit him? I can sorta understand why Paolo might, he's injured and frustrated.

[KofQ]

Right, then can we all agree that it is inappropriate to strongly predict when a human clinical trial might begin even BEFORE the data (even preliminary data) is in showing efficacy in an appropriate animal model?

I see nothing wrong with being cautious in our evaluations of what might or might not work in chronic SCI so as not to engender false hope. I would like to point out yet again that chronic SCI is a very special situation and one cannot and should not extrapolate that what works at acute stages will necessarily work at chronic stages.

If you are planning on testing a therapy as part of a combination, and have safety data from humans already, proving efficacy of the new therapy (in this case, Cethrin) alone is unnecessary and of little practical relevance.

There is no evidence that Ch'ase has any effect in chronic complete contusion injuries unless it is part of a combination. How do you propose to convince the FDA or any IRB to allow you to test Ch'ase on humans without starting with complete injuries first? Moreover, how do you propose to convince a cohort of patients to agree to participate in a clinical trial that is not likely to help them, and could possibly harm them?

I agree that it is inappropriate to strongly predict when a human clinical trial might begin even before the data (even preliminary data) is in showing efficacy in an appropriate animal model.

From 12/12/2011:

CHONDROITINASE + INTENSIVE REHAB is now going forward with help from the ISRT especially for chronic patients. In the future, various forms of FES can be added for further control.

Highly inappropriate indeed...