ChinaSCINet Update

[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]

Originally Posted by 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

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]

Originally Posted by Wise Young

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.

Originally Posted by paolocipolla

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]

Originally Posted by Wise Young

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

[paolocipolla]

Originally Posted by 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,

I am afraid that you missed the last part of my post where I say:

"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."

Then I agree with you that one of the reasons why funding for chronic spinal cord injury studies is limited is because there are nihilists saying that no therapy will work on chronic spinal cord injury.
In fact, as you know, I have requested SCI orgs to restrict founding to research project focusing on chronic SCI and I keep bringing up this issue when I can as I believe it if very unethical for SCI orgs to take donations from people with chronic SCI and spend the money for acute SCI which is what is still happening most of the times with all the SCI orgs and I wonder why so few SCI advocated have taken action to fix this non sense.

Paolo

[Leif]

If not for Wise – I think none of us (or any) would know anything about SCI fixing stuff (science), let alone SCI issues when it comes to daily living issues (care etc,). - I happen to live in one of the best countries when it comes to SCI-care, a very good and a great place with SCI-units etc. - I also happen to know a fellow in 2005, at CC, namely dr. Young. Thereafter, (short story long) I too was in an opposition, like a kid on the block not knowing anything, about anything. - But dr. Young has overwhelmed me by so much what he has contributed here on CC and otherwise – I’m an engineer and have been around in my life, please do not misunderstand me – that I am in total awe of what that man (a person) does. - I thought that I was clever, had stamina - on anything I was doing, projects etc. and didn’t give up (before SCI and after) and took all problems as challenges. But very honestly, - I have met a man, whom does much better, much better, than any, and he does not even have a spinal cord injury.
- I have not said this before, -and I’ve been around in life – but never ever have I met a so dedicated person like dr. Wise Young. A super dedicated doctor, not dedicated solely on SCI cures, - but a doctor that knows more than any about anything when it comes to spinal cord injuries. Anything. And any should be proud to have dr. Young, for example as a guide on Ph.D.’s (I don’t, sail in that league), or anything when it comes to medical classes - I personally have not seen such a knowledgeable person in my life. And such a good person in my life. Never. This though doesn’t mean that I am a true believer of any or anything. I am a person too - I have read books up and down and I am working with the best and a lot of good things. I am not a” blind follower “etc. etc., But if not for Dr. Wise Young, I would have known little nor anything, to question any or to do what I like to do. - I am a hard nail, but I tell, only this time - folks - thank you Dr Wise Young for you’re efforts. You are a great person. And if I can help you sometime in you’re life, count on me. I am honored to be a friend of you Wise. Nuff said! Leif Arild

[Jim]

I removed a lot of back-and-forth bs.

For those of you who continue to attack others, don't be surprised when your posting privileges are revoked.

[ineedmyelin]

Originally Posted by Jim

I removed a lot of back-and-forth bs.

For those of you who continue to attack others, don't be surprised when your posting privileges are revoked.

Just a suggestion, why not create a "Rants & Raves" forum? Its getting annoying to have to wade through so much useless hot air just to get to something useful and meaningful.

[dorsal fin]

True what leif says.Why do you constantly attack and question dr Wise youngs' work paolo? I understand your frustration, I do too as I am C6 incomplete, but this isn't the right way to approach this problem. When I was in rehab centre last christmas there was courses about stem cell technology and sci research and dr Wise Young was mentioned alot. I think dr Wise Young is the one that can save us with the help of donations.