ChinaSCINet Update

[Wise Young]

Jerry,

May I respectfully suggest that there has been a major misunderstanding. Paolo and you seem to have misinterpreted my statements as saying that we are going to test Cethrin and MUSE in our clinical trials whereas I have consistently said over and over against that we are considering candidates for clinical trial and that these two therapies are currently the most promising candidates.

I have indicated that a lot more work is necessary before these treatments can be taken to trial, that we are planning animal studies, and that we are considering other candidates as well. If you have candidates for our 2014 trials, we would be very glad to consider them.

I have tried to bring up a discussion concerning Chondroitinase and have indicated that my willingness to push for that therapy for our 2014 trials. For some reason, you do not seem to want to push that candidate any more. I would be very glad to consider any other candidates that you might have.

You have indicated that you have a new therapy and I am looking forward to evaluating the evidence for that therapy so that we can take it to trial. Assuming that your animal studies are positive for chronic spinal cord injury, it would still have to undergo Phase I/II studies, including large animal safety studies. Also, China does not allow first-in-human phase I trials of therapies from overseas and so Phase I/II trials will have to be done elsewhere.

Thank you but let's get this discussion back on track.

Wise.

Originally Posted by jsilver

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

[muskie]

Originally Posted by Wise Young

Jerry,

May I respectfully suggest that there has been a major misunderstanding. Paolo and you seem to have misinterpreted my statements as saying that we are going to test Cethrin and MUSE in our clinical trials whereas I have consistently said over and over against that we are considering candidates for clinical trial and that these two therapies are currently the most promising candidates.

I have indicated that a lot more work is necessary before these treatments can be taken to trial, that we are planning animal studies, and that we are considering other candidates as well. If you have candidates for our 2014 trials, we would be very glad to consider them.

I have tried to bring up a discussion concerning Chondroitinase and have indicated that my willingness to push for that therapy for our 2014 trials. For some reason, you do not seem to want to push that candidate any more. I would be very glad to consider any other candidates that you might have.

You have indicated that you have a new therapy and I am looking forward to evaluating the evidence for that therapy so that we can take it to trial. Assuming that your animal studies are positive for chronic spinal cord injury, it would still have to undergo Phase I/II studies, including large animal safety studies. Also, China does not allow first-in-human phase I trials of therapies from overseas and so Phase I/II trials will have to be done elsewhere.

Thank you but let's get this discussion back on track.

Wise.

Dr Silver, I believe Dr Young has offered you an olive branch. I hope you take this opportunity to become a collaborating team the whole SCI chronic community would be grateful.

Respectfully,

Kevin

[kz]

Dear Dr. Young ,
Hi, hope you are doing well. Thanks for your reply and explanation and clarification . I did not know that " already paralysed dog" trial are that hard and takes that much time , thanks for clarification , i thought whitin few months we know the answers (sorry for any misunderstanding ). I was not suggesting any other therapy in my post , i was asking about dogs that are already have sci , because i thought that way we might know sooner whether cethrin works for chronics sci asia a or not , and i appreciate your explanation.
I can not thank you enough for all the things you do for us ; as i said once before, this community may never find better friend than you. Thanks so much indeed , and have a great day.

[Geoman]

Wise,
I just want to say, your integrity is very inspiring.
Thank you,
Geoman

[Wise Young]

Originally Posted by kz

Dear Dr. Young ,
Hi, hope you are doing well. Thanks for your reply and explanation and clarification . I did not know that " already paralysed dog" trial are that hard and takes that much time , thanks for clarification , i thought whitin few months we know the answers (sorry for any misunderstanding ). I was not suggesting any other therapy in my post , i was asking about dogs that are already have sci , because i thought that way we might know sooner whether cethrin works for chronics sci asia a or not , and i appreciate your explanation.
I can not thank you enough for all the things you do for us ; as i said once before, this community may never find better friend than you. Thanks so much indeed , and have a great day.

kz, you are very welcome. This discussion is actually very good because it is exposing the dynamics of what is necessary and sufficient to take a therapy to clinical trial. Some believe that we should take all spinal cord injury therapy into large animal efficacy studies before we are allowed to test them in human clinical trials. Others believe that as long as a therapy is safe and has a reasonable rationale for having beneficial effects, they should be allowed into clinical trial. The latter, by the way, is the current attitude of the U.S. FDA although some scientists are trying to change this and impose their criteria for efficacy on therapies before the FDA would approve such trials.

I believe that we should do clinical trials on therapies that have the most evidence for safety and efficacy for chronic spinal cord injury. At the same time, I have a real sense of urgency that clinical trials must go on, as long as the therapies are safe. We also need to do clinical trials to identify therapies that are not effective, so that people don't waste time, money, and hope on them.

Please understand that I am one of the strongest advocates of animal spinal cord injury studies, having developed the most widely used rat spinal cord injury model in the field. However, I know that we can test therapies in animal models forever and we will probably throw away therapies that may work in humans but do not in rodents. The choice of what therapy to test and what clinical trial design to use is very important.

I welcome a diversity of opinions on this subject but hope that people will stop the personal back-biting and attacks. Obviously, feelings are running strongly but we are spending too much time trying to resolve personality issues and deciding who insulted whom. The decisions that are being made regarding choices of therapies to take to trial and how they are being tested are too important to submerge in the tit-for-tat exchanges that are going on.

At stake are several important issues. How much efficacy and safety data must one have before a treatment is taken to clinical trial? Does one have to have large animal efficacy studies for all therapies (as well as the already require large animal safety studies)? What is the minimum safety that all therapies must fulfill before they go to trial? Should we be studying only acute spinal cord injuries in clinical trials? Who should be deciding these questions? What are appropriate controls? These are the questions that we should be discussing.

Wise.

[KofQ]

I recently read this paper (attached) by Hongyun Huang that makes a pretty good case for advancing therapies to the clinic. He also makes a good point that many patients are looking for a complete cure when functionality is most likely to be restored incrementally. If one therapy restores walking with some regularity and another may restore bladder or sexual function later on, would anyone really turn their nose up at the first therapy because it is not good enough? If a therapy could get chronic ASIA A patients to the point where they could walk with crutches or a walker, would you turn that down?
Too many people are looking for a home run in a game that is going to be won with singles and doubles.

[peterf]

After years and decades of if's. could's, possibility, mights, potentials,

Any word about does and is proven to would be highly appreciated.

[ineedmyelin]

Originally Posted by Wise Young

Jerry,

May I respectfully suggest that there has been a major misunderstanding. Paolo and you seem to have misinterpreted my statements as saying that we are going to test Cethrin and MUSE in our clinical trials whereas I have consistently said over and over against that we are considering candidates for clinical trial and that these two therapies are currently the most promising candidates.

I have indicated that a lot more work is necessary before these treatments can be taken to trial, that we are planning animal studies, and that we are considering other candidates as well. If you have candidates for our 2014 trials, we would be very glad to consider them.

I have tried to bring up a discussion concerning Chondroitinase and have indicated that my willingness to push for that therapy for our 2014 trials. For some reason, you do not seem to want to push that candidate any more. I would be very glad to consider any other candidates that you might have.

You have indicated that you have a new therapy and I am looking forward to evaluating the evidence for that therapy so that we can take it to trial. Assuming that your animal studies are positive for chronic spinal cord injury, it would still have to undergo Phase I/II studies, including large animal safety studies. Also, China does not allow first-in-human phase I trials of therapies from overseas and so Phase I/II trials will have to be done elsewhere.

Thank you but let's get this discussion back on track.

Wise.

Classy and very professional, your a great man Dr. Young! Please don't change.

[JohnMarz]

Originally Posted by Wise Young

Hi, kz. Let me first emphasize that we are currently looking at candidates for clinical trial for 2014 when I anticipate that recruitment for the currently planned umbilical cord blood mononuclear cell and lithium trial will be completed.

Has recruitment begun for the umcb+lithium trial in the US?

[Jim]

John, the data from the Phase 2 trial in Hong Kong/China will be available in November. This data is necessary for approval from the U.S. FDA to begin trials here. Recruitment won't be until 2013.