ChinaSCINet Update

[paolocipolla]

Paolo,

Are you dissatisfied with my communication skills or suggesting that I am misleading people? There is a difference.

The audience of the cure forum is rather complex as you have new SCI, old SCI, all with different levels of education and differnt kind of education. Then you have people form different cultures, differen lenguges etc, some people are desperate more than others, so they tend to have more selective perception/reading than others, so I think that communicating with this complex audience it's not an esy task, so you want to be always as clear as possible keeping the lenguage as clear as possible to get out messages easily understadable by all. Then it is essential to monitor how messages are received and do appropriate corrections if needed, but the sender of the message is the one who has to do the whole work with empaty (then, maybe, a communication profetional is required).
Wise I think you know all this better than me, so I wonder why you are reacting in a defensive way. IMO you should take criticism in a more constructive way, but it seems you push your head deeper into the send sometimes

Regarding your comments in blue, may I suggest that you raise some funds for clinical trials in Italy before you criticize how ChinaSCINet has been conducted. If there is anything that you don't understand, I would be more than glad to answer your questions as best as I can but I cannot take any of your comments seriously until you show that you understand what it takes to raise the funds for and to do clinical trials. By the way, if you think that I am being unfair to you by asking you to do this, please look what Christopher Reeve did from 1996-2004. He raised over $100 million for spinal cord injury research during this period. Christopher was not so different from you. In fact, he was actually much worse off than you because he was much more severely injured and had no means of supporting his care and family.

Wise.

Wise,
I am not sure I follow you when you compare me with Christopher Reeeve...

About your suggestion that I raise some funds for clinical trials in Italy you should know the story and I don't think it is usefull to put it here in a public forum (as it is also rather confidential), but if you forgot it or some CC members want to know something about it just contact me via skype.

Paolo

[paolocipolla]

Regarding ChinaSCINet, several things have been going on in the past month:

1. We have had several meetings now with the senior leadership of the Ministry of Health in China. They have given us some good and frank advice that we are now scrambling to implement, including setting up facilities in China to process cells and identifying a Chinese principal investigator for the trial.

2. A major fundraiser is being planned for March 2013 in Hong Kong. We are applying for several possible grants from China.

3. I will be attending the “The International Neural Regeneration Symposium 2012 (INRS2012)” to be held in Shenyang on September 22-25. Further options for the therapies to be tested in 2014 will be discussed.

Wise.

Wise,

here you sound as if they have put you in line

Paolo

[Jawaid]

Wise is my injury complete or incomplete and what about my kind of injury and treatment from Dr Zhu? Ha she treated chronic lumbar injuries?

[Wise Young]

Wise is my injury complete or incomplete and what about my kind of injury and treatment from Dr Zhu? Ha she treated chronic lumbar injuries?

Jawaid,

I believe that you have a conus injury. The concept of "complete" and "incomplete" does not apply to a conus injury, since "complete" usually refers to extent of white matter damage. At the present, I don't think that Dr. Zhu has any therapy that is effective sacral injuries. As you know, she has been focusing on walking rather than bowel/bladder/sexual function. People with conus injuries can walk.

Wise.

[Wise Young]

Wise,
I am not sure I follow you when you compare me with Christopher Reeeve...

About your suggestion that I raise some funds for clinical trials in Italy you should know the story and I don't think it is usefull to put it here in a public forum (as it is also rather confidential), but if you forgot it or some CC members want to know something about it just contact me via skype.

Paolo

Paolo,

I don't think that I am being defensive. You have been critical of what I have said and have been less than constructive with your criticisms. For 15 years, I have answered questions as accurately and clearly as I can on these forums. Imight thought that a figure that I posted from a published paper represented recovery of a specific patient. I explained that the pictures illustrate the Kunming Locomotor Scale and do not represent recovery in patients that undergo this training. Unfortunately, you have suggested that I am misleading people or saying things just to raise money or optimism. That why I am asking whether you are suggesting that I need to improve my communication skills or that I am misleading people.

Regarding my suggestion that you raise some money for trials before you get on a high horse and criticize what others do, I of course know your story and what happened in Italy. That was why I brought up Christopher Reeve. Do you think that it was easy for Christopher to do what he did? He could have gone the same route that you did or what 99.9% of people with spinal cord injury did. He could have gotten angry and felt sorry for himself. He didn't. As he said, he played the hand that he was dealt as best as he could. It was not a great hand but he played it hard and well. If clinical trials were easy, it would have been done already.

Wise.

[Jawaid]

Wise why dont u try conus injuries in your phase3 trials either in india or norway? Why dont u combine therapy in phase3 which can regenerate axons along with umbilical cells? What is wrong in trying lumbar injuries or conus injuries in ur trial?

[Wise Young]

Wise why dont u try conus injuries in your phase3 trials either in india or norway? Why dont u combine therapy in phase3 which can regenerate axons along with umbilical cells? What is wrong in trying lumbar injuries or conus injuries in ur trial?

Jawaid, because the treatment for conus injuries will require neuronal replacement. The umbilical cord blood mononuclear cells and lithium treatment is supposed to stimulate long-tract regeneration, not replace neurons. That is why we restrict the trial to patients who have C5 through T11. As I have indicated, we are developing a lumbosacral spinal cord injury model in rats and plan to test therapies specifically for that model. This will take time and needs to be done.

Wise.

[paolocipolla]

[QUOTE=Wise Young;1559369]Paolo,

I don't think that I am being defensive. You have been critical of what I have said and have been less than constructive with your criticisms. For 15 years, I have answered questions as accurately and clearly as I can on these forums. Imight thought that a figure that I posted from a published paper represented recovery of a specific patient. I explained that the pictures illustrate the Kunming Locomotor Scale and do not represent recovery in patients that undergo this training. Unfortunately, you have suggested that I am misleading people or saying things just to raise money or optimism. That why I am asking whether you are suggesting that I need to improve my communication skills or that I am misleading people.

Wise you are right about not being defensive, you are attaching now.

If you think your communication is clear enough then I have to consider the idea that you are misleding people, but I never said that.
I think you need to get a high experinced communication analist to analize your communication.

Regarding my suggestion that you raise some money for trials before you get on a high horse and criticize what others do, I of course know your story and what happened in Italy. That was why I brought up Christopher Reeve. Do you think that it was easy for Christopher to do what he did? He could have gone the same route that you did or what 99.9% of people with spinal cord injury did. He could have gotten angry and felt sorry for himself. He didn't. As he said, he played the hand that he was dealt as best as he could. It was not a great hand but he played it hard and well. If clinical trials were easy, it would have been done already.

I am sorry Wise, but it seems you are not well informed about what happened in Italy. If you are interested I can brief you on skype when you have time.
...and you are 100% wrong about the route I took. Probably the route I took is similar to the one of C. Reeve, but I am not C. Reeve.

Paolo

[paolocipolla]

My answers are embedded.

Quote:
Originally Posted by KofQ [IMG]/forum/images/buttons/viewpost.gif[/IMG]
Dr Young,

I have a few questions when you get a minute.

1. Have there been any additional adverse events since you last reported them in April?
[No.

2. You mentioned having to find a Chinese principal investigator as well as a Chinese entity to process the cells. Who are doing these things now?
The cells are currently being processed in San Diego and then shipped to China. The doctors in the hospitals are the principal investigators for our current trials. We are currently scrambling to set up a processing center and to identify a Chinese principal investigator that all the other investigators will accept. We can't apply for an IND with the Chinese Ministry of Health until we have done both.

3. You mentioned using Cethrin in a planned Phase 2 trial in NJ. Do you plan on administering the Cethrin on top of the dura as was done in previous trials?
Yes, we are planning to put the Cethrin with fibrin on the dura. That was what was shown to be safe and to produce some recovery in patients in a phase I/II trial. Note that all three therapies (UCMBC, lithium, and Cethrin) have undergone phase I and II trials and shown to be safe.

4. Do you think that the planned phase 2 trials in NJ and/or TX will impact the start date for the phase 3 trials?
I hope not. By the time these phase II trials have finished their recruitment and treatment phase, CN103, US103, and NO103, and IN103 trials should be ready to go. The 2013 phase 3 trial does not depend on either of these two phase II trials. The results of the phase II trials should be available in time for the 2014 trials.

Thanks very much for all your hard work and best of luck with the trials.
You are very welcome. ************************************************** ****

Wise about point #3 above I am afraid you are mixing acute SCI with chronic SCI again.
What happened to the pre-clinical studies of Cethrin that you said you are going to do?
There is no known effect of Cetrhin at chronic stages.
While this treatment will likely be safe I am afraid there is very little chance for efficacy.

Paolo

[Wise Young]

Wise about point #3 above I am afraid you are mixing acute SCI with chronic SCI again.
What happened to the pre-clinical studies of Cethrin that you said you are going to do?
There is no known effect of Cetrhin at chronic stages.
While this treatment will likely be safe I am afraid there is very little chance for efficacy.

Paolo,

I am not mixing acute and chronic. I am talking about plans. We will be doing chronic animal studies with Cethrin. The phase I/II Cethrin studies showed that the treatment can be safely administered in people with subacute spinal cord injury. Cethrin has not been studied in people or animals with chronic SCI. Why are you afraid that there is very little chance for efficacy in chronic SCI? You don't know and we will find out, first in animals and then in humans.

Wise.

[CarolinaB]

Dr. Wise,

Can you share the 6 week dosing regiman(s) that are currently being used for lithium in the ChinaSCINet studies, or is that remaining confidential?

Also, is the umbilical cord blood being used for the studies filtered for only certain types of cells, or for all the various stem cells?

Thank you for your persistant efforts for so many!
Regards,
Carolina

[Wise Young]

Dr. Wise,

Can you share the 6 week dosing regiman(s) that are currently being used for lithium in the ChinaSCINet studies, or is that remaining confidential?

Also, is the umbilical cord blood being used for the studies filtered for only certain types of cells, or for all the various stem cells?

Thank you for your persistant efforts for so many!
Regards,
Carolina

Carolina, the lithium dosing has been published in two papers reporting the results of the safety and the efficacy of lithium alone in chronic spinal cord injury. The papers describe in detail the dosing schedule and monitoring that we do. I list the abstracts of the papers below.

I do not recommend that people take lithium without physician supervision. The protocol is similar to what is used to titrate the dose of lithium for treating manic depression. If you have a doctor has read these papers and have questions, I would be glad to answer them.

Wise.

Reference

1. Yang ML, Li JJ, So KF, Chen JY, Cheng WS, Wu J, Wang ZM, Gao F and Young W (2012). Efficacy and safety of lithium carbonate treatment of chronic spinal cord injuries: a double-blind, randomized, placebo-controlled clinical trial. Spinal Cord 50: 141-6. Department of Spinal and Neural Function Reconstruction, China Rehabilitation Research Center, Beijing, China. STUDY DESIGN: Lithium has attracted much attention as a neuroregenerative agent for spinal cord injury in animal models. We hypothesized that the lithium can be beneficial to patients with spinal cord injury. The safety and pharmacokinetics of lithium has been studied in our earlier phase I clinical trial, indicating its safety. This is a phase II clinical trial to evaluate its efficacy on chronic spinal cord injury patients. OBJECTIVES: The aim of this study was to investigate the efficacy of lithium on chronic spinal cord injury patients. SETTING: A major spinal cord injury rehabilitation center in Beijing, China. METHODS: Randomized, double-blind, placebo-controlled 6-week parallel treatment arms with lithium carbonate and with placebo. A total of 40 chronic spinal cord injury subjects were recruited. Oral lithium carbonate was titrated or placebo was simulated to maintain the serum lithium level of 0.6-1.2 mmol l(-1) for 6 weeks, followed by a 6-month follow-up. The functional outcomes and the neurological classifications, as well as the safety parameters, adverse events and pharmacokinetic data were carefully collected and monitored. RESULTS: No significant changes in the functional outcomes and the neurological classifications were found. The only significant differences were in the pain assessments using visual analog scale comparing the lithium and the placebo group. No severe adverse event was documented in the study. CONCLUSION: The lithium treatment did not change the neurological outcomes of patients with chronic spinal cord injury. It is worth to investigate whether lithium is effective in the treatment of neuropathic pain in chronic spinal cord injury. SPONSORSHIP: China Spinal Cord Injury Network Company Limited.

2. Wong YW, Tam S, So KF, Chen JY, Cheng WS, Luk KD, Tang SW and Young W (2011). A three-month, open-label, single-arm trial evaluating the safety and pharmacokinetics of oral lithium in patients with chronic spinal cord injury. Spinal Cord 49: 94-8. Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, China. yatwa@hku.hk. OBJECTIVES: Lithium has recently been found to enhance neuronal regeneration and differentiation. This arouses its potential use to treat spinal cord injury patients. The safety and pharmacokinetics of lithium are not verified for this group of patients as their internal organ functions may change. This is a phase 1 clinical trial to evaluate the safety and pharmacokinetics of lithium in spinal cord injury patients. METHODS: A total of 20 chronic spinal cord injury subjects were recruited. Oral lithium carbonate was given in divided dose to maintain the serum lithium level 0.6-1.2 mmol l(-1) for 6 weeks. Safety parameters, adverse events and pharmacokinetic data were carefully collected and monitored. RESULTS: No severe adverse event was documented. All blood parameters remained stable. Nausea and vomiting were the most common complaints but tolerance was improved in 2 weeks for most subjects. A wide range of oral doses was required to maintain serum lithium level at the targeted range. However, the dose for individual subject was relatively constant. CONCLUSION: This phase 1 clinical trial is the first report indicating the safety of lithium in chronic spinal cord injury patients. It is well tolerated after the first 2 weeks. Individual titration of lithium is essential to maintain an optimal serum lithium level but once the desirable level is achieved, the oral dose remains relatively unchanged for maintenance.

[paolocipolla]

Paolo,

I am not mixing acute and chronic. I am talking about plans. We will be doing chronic animal studies with Cethrin. The phase I/II Cethrin studies showed that the treatment can be safely administered in people with subacute spinal cord injury. Cethrin has not been studied in people or animals with chronic SCI. Why are you afraid that there is very little chance for efficacy in chronic SCI? You don't know and we will find out, first in animals and then in humans.

Wise.

Wise,

in my opinion you are putting the horse before the cart.
How can you plan clinical trials for 2014 with Cethrin if you don't know yet if it has any effect on chronic SCI animals?
To me it sounds as if I plan to run the New York marathon in 2014 when there is no cure yet for chronic SCI.

Cethrin has been around for many years now, how come no one has done a single study with Cethrin on animals with chronic SCI?

Here are possible answers I can think of in this moment:

1) researchers think there is very little chances of efficacy in chronic SCI
2) researchers are idiots
3) researchers don't give a damn about us living with chronic SCI
4) all the 3 above..

What do you think?

In any case I would like to see serious studies done with cethrin on animals with chronic SCI ASAP and if there will be indications of efficacy I would like to see Cethrin in clinical trials for chronic SCI ASAP.

Paolo

[Wise Young]

Paolo,

We have proposed a series of studies that would lead to clinical trials of the combination of UCBMC, lithium, and Cethrin, if the experiments work. Why are you so opposed to planning for clinical trials so that the preclinical results go directly to trial if they are successful?

You seem to be convinced that Cethrin does not work even though you have no data to suggest that it does not work. No data does not mean that it will not work. It simply means no data. We will get this data. If the animal experiments don't show any benefit, we go to another therapy.

If our results support safety and efficacy of the combination treatment, we plan to move ahead quickly without having to wait a year or two for the fundraising and submitting for regulatory approval. Planning ahead eliminates delays.

To use your analogy of running in the New York marathon, we both agree that we won't be running in the marathon in 2014 if we don't prepare seriously for the marathon. If we fail, you can say "I told you that you can't do it" but please don't start saying that we will fail before we even start.

Finally, regarding why nobody has studied Cethrin in chronic animal spinal cord injury, have you considered the possibility that funding for chronic spinal cord injury studies is limited because there are nihilists saying that no therapy will work on chronic spinal cord injury?

Wise.

Wise,

in my opinion you are putting the horse before the cart.
How can you plan clinical trials for 2014 with Cethrin if you don't know yet if it has any effect on chronic SCI animals?
To me it sounds as if I plan to run the New York marathon in 2014 when there is no cure yet for chronic SCI.

Cethrin has been around for many years now, how come no one has done a single study with Cethrin on animals with chronic SCI?

Here are possible answers I can think of in this moment:

1) researchers think there is very little chances of efficacy in chronic SCI
2) researchers are idiots
3) researchers don't give a damn about us living with chronic SCI
4) all the 3 above..

What do you think?

In any case I would like to see serious studies done with cethrin on animals with chronic SCI ASAP and if there will be indications of efficacy I would like to see Cethrin in clinical trials for chronic SCI ASAP.

Paolo

[CarolinaB]

Carolina, the lithium dosing has been published in two papers reporting the results of the safety and the efficacy of lithium alone in chronic spinal cord injury. The papers describe in detail the dosing schedule and monitoring that we do. I list the abstracts of the papers below.

I do not recommend that people take lithium without physician supervision. The protocol is similar to what is used to titrate the dose of lithium for treating manic depression. If you have a doctor has read these papers and have questions, I would be glad to answer them.

Wise.

Reference

1. Yang ML, Li JJ, So KF, Chen JY, Cheng WS, Wu J, Wang ZM, Gao F and Young W (2012). Efficacy and safety of lithium carbonate treatment of chronic spinal cord injuries: a double-blind, randomized, placebo-controlled clinical trial. Spinal Cord 50: 141-6. Department of Spinal and Neural Function Reconstruction, China Rehabilitation Research Center, Beijing, China. STUDY DESIGN: Lithium has attracted much attention as a neuroregenerative agent for spinal cord injury in animal models. We hypothesized that the lithium can be beneficial to patients with spinal cord injury. The safety and pharmacokinetics of lithium has been studied in our earlier phase I clinical trial, indicating its safety. This is a phase II clinical trial to evaluate its efficacy on chronic spinal cord injury patients. OBJECTIVES: The aim of this study was to investigate the efficacy of lithium on chronic spinal cord injury patients. SETTING: A major spinal cord injury rehabilitation center in Beijing, China. METHODS: Randomized, double-blind, placebo-controlled 6-week parallel treatment arms with lithium carbonate and with placebo. A total of 40 chronic spinal cord injury subjects were recruited. Oral lithium carbonate was titrated or placebo was simulated to maintain the serum lithium level of 0.6-1.2 mmol l(-1) for 6 weeks, followed by a 6-month follow-up. The functional outcomes and the neurological classifications, as well as the safety parameters, adverse events and pharmacokinetic data were carefully collected and monitored. RESULTS: No significant changes in the functional outcomes and the neurological classifications were found. The only significant differences were in the pain assessments using visual analog scale comparing the lithium and the placebo group. No severe adverse event was documented in the study. CONCLUSION: The lithium treatment did not change the neurological outcomes of patients with chronic spinal cord injury. It is worth to investigate whether lithium is effective in the treatment of neuropathic pain in chronic spinal cord injury. SPONSORSHIP: China Spinal Cord Injury Network Company Limited.

2. Wong YW, Tam S, So KF, Chen JY, Cheng WS, Luk KD, Tang SW and Young W (2011). A three-month, open-label, single-arm trial evaluating the safety and pharmacokinetics of oral lithium in patients with chronic spinal cord injury. Spinal Cord 49: 94-8. Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, China. yatwa@hku.hk. OBJECTIVES: Lithium has recently been found to enhance neuronal regeneration and differentiation. This arouses its potential use to treat spinal cord injury patients. The safety and pharmacokinetics of lithium are not verified for this group of patients as their internal organ functions may change. This is a phase 1 clinical trial to evaluate the safety and pharmacokinetics of lithium in spinal cord injury patients. METHODS: A total of 20 chronic spinal cord injury subjects were recruited. Oral lithium carbonate was given in divided dose to maintain the serum lithium level 0.6-1.2 mmol l(-1) for 6 weeks. Safety parameters, adverse events and pharmacokinetic data were carefully collected and monitored. RESULTS: No severe adverse event was documented. All blood parameters remained stable. Nausea and vomiting were the most common complaints but tolerance was improved in 2 weeks for most subjects. A wide range of oral doses was required to maintain serum lithium level at the targeted range. However, the dose for individual subject was relatively constant. CONCLUSION: This phase 1 clinical trial is the first report indicating the safety of lithium in chronic spinal cord injury patients. It is well tolerated after the first 2 weeks. Individual titration of lithium is essential to maintain an optimal serum lithium level but once the desirable level is achieved, the oral dose remains relatively unchanged for maintenance.

Dr. Wise,

Thank you kindly for including all of this information and guidance!

Best regards,
Carolina