ChinaSCINet Update

[taymas]

To be clear, Tongren Hospital is not offering cell injections.

I'm still packing my bags.

[carlosar]

Dear Dr Wise
You writed on post 12-25-2014, 09:37 PM " that results of clinical trial subjectct tha "no walking training did not walk" but what happen with spasticity? there a decrease of in all subject?
Best regrads an have a great 2015

[Wise Young]

What are considered the road blocks to normalcy? Not saying i or anyone should expect to be "back to normal" but if a spinal cord is shown to be able to be restored, what exactly prevents it from ever becoming "normal"?

Eric.S,

Our trials suggest that the obstacle is in the rehabilitation. We trained the subjects to walk in Kunming and 75% walked. We did not train the subjects to walk in Hon Kong and none walked. We did not train the subjects to move their arms or legs voluntarily and, despite being able to walk long distances using a rolling walker with on assistance, none of the subjects could move their legs as well when lying down. So, we are now considering how to enhance voluntary function using functional electrical stimulation (FES) and also vibratory stimulation (which activates proprioceptive input into the spinal cord). Both FES and whole body vibration have been reported to improve functional recovery after acute spinal cord injury. We hope that they will also facilitate recovery after umbilical cord blood mononuclear cell transplants in people with chronic spinal cord injury. Wise.

Wise.

[Wise Young]

Dear Dr Wise
You writed on post 12-25-2014, 09:37 PM " that results of clinical trial subjectct tha "no walking training did not walk" but what happen with spasticity? there a decrease of in all subject?
Best regrads an have a great 2015

There was no significant change in spasticity in the subjects treated with umbilical cord blood mononuclear cell transplants. These are all people with chronic complete spinal cord injury and few had severe spasticity. In China, they don't usually give a lot of drugs for spasticity and none had severe spasticity before the treatment. There have been reports that spasticity decreases with intensive walking exercise but we did not see such decreases in our subjects. Wise.

[JamesMcM]

Eric.S,

Our trials suggest that the obstacle is in the rehabilitation. We trained the subjects to walk in Kunming and 75% walked. We did not train the subjects to walk in Hon Kong and none walked. We did not train the subjects to move their arms or legs voluntarily and, despite being able to walk long distances using a rolling walker with on assistance, none of the subjects could move their legs as well when lying down. So, we are now considering how to enhance voluntary function using functional electrical stimulation (FES) and also vibratory stimulation (which activates proprioceptive input into the spinal cord). Both FES and whole body vibration have been reported to improve functional recovery after acute spinal cord injury. We hope that they will also facilitate recovery after umbilical cord blood mononuclear cell transplants in people with chronic spinal cord injury. Wise.

Wise.

That makes a lot of sense. But in the phase II trial you also stated that a few subjects regained some bowel and bladder control, I don't believe you made any statements about functional training in reguards those early functions via biofeedback or something. Any idea why the subjects seen return with those functions, even though there was actually no functional rehab after cell transplants?

[Martin]

"Also, I want to say that we are seriously considering expanding our trial to Australia and New Zealand"
Hi Dr Young
Thankyou so much for your great work, I have been following all your posts for 15 years and met you in Sydney when CR was out. I don't post much to you as I never want to use any of your precious time on reading my post that could be used for the ultimate goal. It's very exciting that you are considering expanding your trial to include Australia & NZ.
Is there any way that we can help make this happen?

[c473s]

Look up Josh in Scone. he should not be hard to find and is working to get better things done in Australia.

"Also, I want to say that we are seriously considering expanding our trial to Australia and New Zealand"
Hi Dr Young
Thankyou so much for your great work, I have been following all your posts for 15 years and met you in Sydney when CR was out. I don't post much to you as I never want to use any of your precious time on reading my post that could be used for the ultimate goal. It's very exciting that you are considering expanding your trial to include Australia & NZ.
Is there any way that we can help make this happen?

[lunasicc42]

wise, youve been kind of cryptic and vague as to what the specific gains have been ...is that because you are protecting the publication process or the trial so far or its not showing significant progress? Either way, you can say and I think we can handle it

Can't you just tell us if it because of no significant results or the publication process

[Tbone57]

Do you think they would expand trials and continue with no results? Would that make sense? I don't know....very confusing

[Jim]

lunasicc, you consider this kind of cryptic and vague?

I decided to combine the phase I and II studies in one report. That took a while to rewrite the manuscript because of the word limitations (3000 words) and because there was a lot of data from both trials to put into one paper. However, I felt that it was important to do this in order to emphasize the main conclusion of our study, i.e. no exercise no walk. If we did not present the Hong Kong data, where 8 subjects who received the transplants but no walking training did not walk. I have to get approval of all the investigators and people involved in the study (now up to 27).

The paper now reports several very important findings. First, transplantation of umbilical cord blood mononuclear cells into the spinal cord is safe in 28 patients with chronic C5-T11 spinal cord injury, including one who turned out to be a C3 incomplete (ASIA C). None of the subjects lost neurological function. Second, a majority (15/20) of the subjects that received locomotor training recovered ability to walk at least 10 meters with minimal assistance in a rolling walker and 7 walk at least 10 meters without assistance. Third, a majority (12/20) regained sufficient bladder and bowel function so that they did not require any assistance for both functions and 11 subjects do not use catheters to empty the bladder compared to only 2 before treatment. In the previous manuscript, I could not talk about the Hong Kong results because that was in a separate manuscript. Reporting the two studies together makes for a much better paper. Of course, I had to obtain the approval of all the investigators.

The delay in publication has nothing to do with the FDA. We closed the database in May 2014 and submitted the first version of the manuscript to a journal in August 2014. It was returned without review. We submitted to two other high-impact journals in September and October and they too return the manuscript without review. So, that was when I decided to combine the two manuscript and submit to a fourth high-impact journal in the hopes that the much improved report will receive a review.

Journals return a manuscript without review when they think that the subject of the paper is too specialized or not suitable for their journal. Sometimes, they don't think that they have the appropriate reviewers. Other times, it may be because they don't think that the paper is good enough for their journal. The decision is made by the editors. The letters explaining their editorial decision all said that they thought the paper would be better submitted to a more specialized journal. So, we are submitting to a more specialized journal.

In the meantime, we are working hard to getting the phase III trial organized and funded. I will address this in another post.

Wise.

[lunasicc42]

Do you think they would expand trials and continue with no results? Would that make sense? I don't know....very confusing

Yes , that is one of the main things that keep me hopeful ...I am 'thinking' that they wouldn't be able to move the trials to phase three unless there were some good initial results ...but thats just my hope ...its not based on anything solid ...and I feel bad because when wise showed videos the feeling of the pitch was like: "see! See! the walking is not robotic at all!". But Honestly everything that I have had the privilege of seeing in these stages look pretty robotic and labored to me. I hope that I am just Jumping the gun and that wise has an ace up his sleeve and I am basing my worries on stale information.

[lunasicc42]

yes Jim I remember that ...you know the mind of a long term quad and the hope of a good treatment can drive the mind wild ...waiting is the haaaardest part!

[Wise Young]

Martin,

We are now discussing IND (initial new drug/device) applications with a CRO (clinical research organization) about applying to for clinical trials in different countries. I of course know many of the groups in Australia. If it looks as if we can get permission to do the trial in Australia, raise the funds, and include Australia in the trial without much expense or trouble, that would be great.

Wise.

"Also, I want to say that we are seriously considering expanding our trial to Australia and New Zealand"
Hi Dr Young
Thankyou so much for your great work, I have been following all your posts for 15 years and met you in Sydney when CR was out. I don't post much to you as I never want to use any of your precious time on reading my post that could be used for the ultimate goal. It's very exciting that you are considering expanding your trial to include Australia & NZ.
Is there any way that we can help make this happen?

[Wise Young]

That makes a lot of sense. But in the phase II trial you also stated that a few subjects regained some bowel and bladder control, I don't believe you made any statements about functional training in reguards those early functions via biofeedback or something. Any idea why the subjects seen return with those functions, even though there was actually no functional rehab after cell transplants?

We did not do any training of bladder and bowel function in our trial. We will need to bring the subjects back for further studies to confirm the mechanisms but apparently the locomotor training in Kunming was associated with bowel and bladder improvement. Note that Susie Harkema's patients in Louisville apparently also have reported improved bladder and bowel function although this was not documented in their published report.

Wise.

[tumbleweeds]

Dan,
I have proposed to Stemcyte (the company providing the umbilical cord blood mononuclear cells) that they apply for expanded use access after the phase III trial starts in 2015. I am working closely with the company to help them expand the production of the cells so that it can treat thousands of people. So far, the company has provided several hundred units of umbilical cord blood for the clinical trials.

Wise.

As I understand it from the above quote that Stemcyte is providing the stem cells for ChinaSCINet. But what is the role of Neuralstem or Geron Corp in ChinaSCINet, if any? I see all three companies are mentioned from time to time but I'm not sure how Neuralstem or Geron are involved. Can someone please clarify?
Thank you.