Spinal Cord Injury Network USA (SCINetUSA)

[flamecarcanet]

Chaz19,

I listened in to this webinar and then downloaded this pdf. It's a lot of information all at once, but it answered questions I didn't even know I had. I think this is so helpful, and this way Dr. Young doesn't have to repeat himself again and again.

Here's the webinar.
http://www.thisabled.com/stem-cell-webinar.php


Here's the pdf slideshow that went with it, updated, so they can be seen well.
http://www.thisabled.com/StemCellWebinar.pdf

I think that would answer your request for layman's history and for updated info on stem cell trials.

--Flame carcanet

[Wise Young]

Jim I was thinking along the lines of how far S.C.I. has come from no hope to getting hope through donations and to see the doctors and researchers explaining the trials lay man terms and showing some patience getting work done and results you hope to get and please do not show a video of happy S.C.I. playing and talking that life is not so bad and saying that this will not get the better of us well i hope not would the researchers not have some animals walking etc. you could explain and show what evidence hoping that the trials will work if you were to put a video on what would it be I pm you my hot mail for a news letter.

skeaman,

I don't feel comfortable showing videos of walking rats or patients, even though I have both. The reason is because rats and people may be walking for reasons other than the treatment. It is always easy to select one example and it is human to think that everybody will respond like the example. Please understand that I am not against companies showing ads with beautiful smiling people using their products. That is marketing. I don't believe that it is a good idea to market experimental therapies that are on clinical trial. I also think that it is not a good idea to give numbers like 70% recovery of rats because the relationship of animal recovery to human recovery is tenuous and depends on both injury type and severity.

On the other hand, I think that it is important that people know that animal studies have shown that the proposed therapy is beneficial in animals, that they are aware of the information concerning safety of the therapy, and they understand rationale for testing the therapy. There is no guarantee of treatment effect or safety. Participating in a clinical trial is a service that people are performing for the community. People are taking a risk on behalf of other people with spinal cord injury. An experimental therapy means that there is not yet convincing data indicating efficacy. They are taking the risk in order to help accelerate the development of therapies for spinal cord injury. That is why the clinical trial does not charge for the therapy. If the therapy works, that is great. If it doesn't work, we need to go on to something else and not waste valuable resources on something that is not safe or effective.

In the case of umbilical cord blood and lithium, there is data from animal studies indicating that mononuclear cells alone and lithium alone are beneficial in spinal cord injury. We hypothesize that the combination of the two treatment would be better than each one alone. That is why the trial will test each of the therapy alone and the two therapies together. In order to ensure the highest likelihood of showing a significant treatment effect, we chose certain inclusion and exclusion criteria that would ensure that the patients have similar injuries. The greater the variability of people in each treatment group, the more subjects we will need to show a significant difference.

The injury type and level also determines which outcome measures can be used. For example, if the study includes people with cervical and thoracic spinal cord injury, we must use an outcome measure that can be applied to both. Obviously, we cannot compare arm function in people with cervical and thoracic spinal cord injuries because the latter will not be affected by the injury. On the other hand, changes in motor and sensory scores are valid for both cervical and thoracic spinal cord injury. Likewise, comparison of walking scores may also be valid because both cervical and thoracic spinal cord injury cause impairment of walking.

Safety considerations play a role in the inclusion and exclusion criteria. For example, we chose to exclude subjects with C4 or higher injuries because our treatment protocol calls for injection of cells above and below the injury site. A person with a C4 injury would require injection of cells into C3, the part of the spinal cord where the phrenic nucleus (that controls breathing) is located. I believe that we would need to do a separate phase 2 clinical trial just for high quads where the cells would be injected into the injury site and below. Such a clinical trial could also focus on motor and sensory recovery in the shoulders and arms. Because of the increased risk of cell injection into the upper cervical spinal cord, I think that it would be better to have more evidence in human trials showing that the treatment is safe and beneficial before doing it in somebody with high cervical injury.

The cause of injury is also important. One of the most important differences between spinal cord injury is whether the lumbosacral gray matter was damaged (the part of the spinal cord where the neurons controlling the legs in the lower spinal cord). The spinal cord ends at vertebral level L1. Below L1, the spinal canal contains only spinal roots. The lumbosacral enlargement is located between T11 and L1 vertebral levels. Injury to this part of the spinal cord may lead to flaccid paralysis with consequent atrophy of muscles in the legs. Lumbosacral injuries may have a different response to treatment than injuries that primarily affect white matter in the lower cervical and upper thoracic spinal cord. The treatment with umbilical cord blood mononuclear cells and lithium is designed primarily for (the mononuclear cells) bridging the injury site and (the lithium) stimulating neurotrophin production. The therapy should stimulate axonal growth.

For people with lumbosacral injuries, we need a different kind of cell therapy, i.e. neural stem cells that can replace neurons. We are working hard on establishing a cell source for neural stem cells. At the present, there are only three sources of neural stem cells. First, embryonic stem cells can be differentiated into neural stem cells. Second, fetal neural stem cells can be obtained from aborted fetuses. Third, adult neural stem cells can be obtained from a person's brain. The first two sources are not immune-compatible. While the last is immune-compatible (if obtained from the brain of the person), it is difficult to jsutify removing part of the brain to treat the spinal cord. By the way, while a number of groups have reported success in making neural stem cells from bone marrow or mesenchymal stem cells, these have not been particularly reproducible nor have the studies provided credible evidence of beneficial effects of such cells in animal spinal cord injury models.

Fortunately, a new option has recently been made available for creating immune-compatible neural stem cells without having to take out a chunk of one's brain. These are induced pluripotent stem (IPS) cells. By insertion of four genes into skin cells (fibroblasts), several groups have shown that it is possible to create embryonic stem cell like pluripotent cells. Unfortunately, much work still needs to be done to ensure the safety of such cells because they have a propensity to grow into tumors when transplanted. We and many other groups are working hard testing IPS cells in animal models and figuring out how to make IPS cells safer. I believe that IPS cells will become available for clinical trials in about 3 years.

Finally, what about other kinds of spinal cord injuries, such as those resulting from ischemia (loss of blood flow) or transverse myelitis (probably inflammation mediated)? I believe that these should not be tested together with traumatic spinal cord injury because both the causes and response of these injuries to umbilical cord blood mononuclear cells and lithium may be different. The best way is to carry out a separate phase 2 trial on people with ischemic and transverse myelitis. Such a trial would be open label and intended to establish safety and feasibility of the cell transplant and lithium therapy for transverse myelitis. Such a clinical trial could be done with about 20 people.

Wise.

[skeaman]

skeaman,

I don't feel comfortable showing videos of walking rats or patients, even though I have both. The reason is because rats and people may be walking for reasons other than the treatment. It is always easy to select one example and it is human to think that everybody will respond like the example. Please understand that I am not against companies showing ads with beautiful smiling people using their products. That is marketing. I don't believe that it is a good idea to market experimental therapies that are on clinical trial. I also think that it is not a good idea to give numbers like 70% recovery of rats because the relationship of animal recovery to human recovery is tenuous and depends on both injury type and severity.

On the other hand, I think that it is important that people know that animal studies have shown that the proposed therapy is beneficial in animals, that they are aware of the information concerning safety of the therapy, and they understand rationale for testing the therapy. There is no guarantee of treatment effect or safety. Participating in a clinical trial is a service that people are performing for the community. People are taking a risk on behalf of other people with spinal cord injury. An experimental therapy means that there is not yet convincing data indicating efficacy. They are taking the risk in order to help accelerate the development of therapies for spinal cord injury. That is why the clinical trial does not charge for the therapy. If the therapy works, that is great. If it doesn't work, we need to go on to something else and not waste valuable resources on something that is not safe or effective.

In the case of umbilical cord blood and lithium, there is data from animal studies indicating that mononuclear cells alone and lithium alone are beneficial in spinal cord injury. We hypothesize that the combination of the two treatment would be better than each one alone. That is why the trial will test each of the therapy alone and the two therapies together. In order to ensure the highest likelihood of showing a significant treatment effect, we chose certain inclusion and exclusion criteria that would ensure that the patients have similar injuries. The greater the variability of people in each treatment group, the more subjects we will need to show a significant difference.

The injury type and level also determines which outcome measures can be used. For example, if the study includes people with cervical and thoracic spinal cord injury, we must use an outcome measure that can be applied to both. Obviously, we cannot compare arm function in people with cervical and thoracic spinal cord injuries because the latter will not be affected by the injury. On the other hand, changes in motor and sensory scores are valid for both cervical and thoracic spinal cord injury. Likewise, comparison of walking scores may also be valid because both cervical and thoracic spinal cord injury cause impairment of walking.

Safety considerations play a role in the inclusion and exclusion criteria. For example, we chose to exclude subjects with C4 or higher injuries because our treatment protocol calls for injection of cells above and below the injury site. A person with a C4 injury would require injection of cells into C3, the part of the spinal cord where the phrenic nucleus (that controls breathing) is located. I believe that we would need to do a separate phase 2 clinical trial just for high quads where the cells would be injected into the injury site and below. Such a clinical trial could also focus on motor and sensory recovery in the shoulders and arms. Because of the increased risk of cell injection into the upper cervical spinal cord, I think that it would be better to have more evidence in human trials showing that the treatment is safe and beneficial before doing it in somebody with high cervical injury.

The cause of injury is also important. One of the most important differences between spinal cord injury is whether the lumbosacral gray matter was damaged (the part of the spinal cord where the neurons controlling the legs in the lower spinal cord). The spinal cord ends at vertebral level L1. Below L1, the spinal canal contains only spinal roots. The lumbosacral enlargement is located between T11 and L1 vertebral levels. Injury to this part of the spinal cord may lead to flaccid paralysis with consequent atrophy of muscles in the legs. Lumbosacral injuries may have a different response to treatment than injuries that primarily affect white matter in the lower cervical and upper thoracic spinal cord. The treatment with umbilical cord blood mononuclear cells and lithium is designed primarily for (the mononuclear cells) bridging the injury site and (the lithium) stimulating neurotrophin production. The therapy should stimulate axonal growth.

For people with lumbosacral injuries, we need a different kind of cell therapy, i.e. neural stem cells that can replace neurons. We are working hard on establishing a cell source for neural stem cells. At the present, there are only three sources of neural stem cells. First, embryonic stem cells can be differentiated into neural stem cells. Second, fetal neural stem cells can be obtained from aborted fetuses. Third, adult neural stem cells can be obtained from a person's brain. The first two sources are not immune-compatible. While the last is immune-compatible (if obtained from the brain of the person), it is difficult to jsutify removing part of the brain to treat the spinal cord. By the way, while a number of groups have reported success in making neural stem cells from bone marrow or mesenchymal stem cells, these have not been particularly reproducible nor have the studies provided credible evidence of beneficial effects of such cells in animal spinal cord injury models.

Fortunately, a new option has recently been made available for creating immune-compatible neural stem cells without having to take out a chunk of one's brain. These are induced pluripotent stem (IPS) cells. By insertion of four genes into skin cells (fibroblasts), several groups have shown that it is possible to create embryonic stem cell like pluripotent cells. Unfortunately, much work still needs to be done to ensure the safety of such cells because they have a propensity to grow into tumors when transplanted. We and many other groups are working hard testing IPS cells in animal models and figuring out how to make IPS cells safer. I believe that IPS cells will become available for clinical trials in about 3 years.

Finally, what about other kinds of spinal cord injuries, such as those resulting from ischemia (loss of blood flow) or transverse myelitis (probably inflammation mediated)? I believe that these should not be tested together with traumatic spinal cord injury because both the causes and response of these injuries to umbilical cord blood mononuclear cells and lithium may be different. The best way is to carry out a separate phase 2 trial on people with ischemic and transverse myelitis. Such a trial would be open label and intended to establish safety and feasibility of the cell transplant and lithium therapy for transverse myelitis. Such a clinical trial could be done with about 20 people.

Wise.

Thanks for replaying boy that is a long letter . I see where you are coming from I think I got the just of it we will just have to wait for 6 or 8 years can you say is that mis leading any body but if you can get fit and able people giving money they like to see what it is going to as I say we must branch out to other people ps i would love to be one of the 20 people as i am sure others would be

[lakboy]

skeaman,

I don't feel comfortable showing videos of walking rats or patients, even though I have both. The reason is because rats and people may be walking for reasons other than the treatment. It is always easy to select one example and it is human to think that everybody will respond like the example. Please understand that I am not against companies showing ads with beautiful smiling people using their products. That is marketing. I don't believe that it is a good idea to market experimental therapies that are on clinical trial. I also think that it is not a good idea to give numbers like 70% recovery of rats because the relationship of animal recovery to human recovery is tenuous and depends on both injury type and severity.

On the other hand, I think that it is important that people know that animal studies have shown that the proposed therapy is beneficial in animals, that they are aware of the information concerning safety of the therapy, and they understand rationale for testing the therapy. There is no guarantee of treatment effect or safety. Participating in a clinical trial is a service that people are performing for the community. People are taking a risk on behalf of other people with spinal cord injury. An experimental therapy means that there is not yet convincing data indicating efficacy. They are taking the risk in order to help accelerate the development of therapies for spinal cord injury. That is why the clinical trial does not charge for the therapy. If the therapy works, that is great. If it doesn't work, we need to go on to something else and not waste valuable resources on something that is not safe or effective.

In the case of umbilical cord blood and lithium, there is data from animal studies indicating that mononuclear cells alone and lithium alone are beneficial in spinal cord injury. We hypothesize that the combination of the two treatment would be better than each one alone. That is why the trial will test each of the therapy alone and the two therapies together. In order to ensure the highest likelihood of showing a significant treatment effect, we chose certain inclusion and exclusion criteria that would ensure that the patients have similar injuries. The greater the variability of people in each treatment group, the more subjects we will need to show a significant difference.

The injury type and level also determines which outcome measures can be used. For example, if the study includes people with cervical and thoracic spinal cord injury, we must use an outcome measure that can be applied to both. Obviously, we cannot compare arm function in people with cervical and thoracic spinal cord injuries because the latter will not be affected by the injury. On the other hand, changes in motor and sensory scores are valid for both cervical and thoracic spinal cord injury. Likewise, comparison of walking scores may also be valid because both cervical and thoracic spinal cord injury cause impairment of walking.

Safety considerations play a role in the inclusion and exclusion criteria. For example, we chose to exclude subjects with C4 or higher injuries because our treatment protocol calls for injection of cells above and below the injury site. A person with a C4 injury would require injection of cells into C3, the part of the spinal cord where the phrenic nucleus (that controls breathing) is located. I believe that we would need to do a separate phase 2 clinical trial just for high quads where the cells would be injected into the injury site and below. Such a clinical trial could also focus on motor and sensory recovery in the shoulders and arms. Because of the increased risk of cell injection into the upper cervical spinal cord, I think that it would be better to have more evidence in human trials showing that the treatment is safe and beneficial before doing it in somebody with high cervical injury.

The cause of injury is also important. One of the most important differences between spinal cord injury is whether the lumbosacral gray matter was damaged (the part of the spinal cord where the neurons controlling the legs in the lower spinal cord). The spinal cord ends at vertebral level L1. Below L1, the spinal canal contains only spinal roots. The lumbosacral enlargement is located between T11 and L1 vertebral levels. Injury to this part of the spinal cord may lead to flaccid paralysis with consequent atrophy of muscles in the legs. Lumbosacral injuries may have a different response to treatment than injuries that primarily affect white matter in the lower cervical and upper thoracic spinal cord. The treatment with umbilical cord blood mononuclear cells and lithium is designed primarily for (the mononuclear cells) bridging the injury site and (the lithium) stimulating neurotrophin production. The therapy should stimulate axonal growth.

For people with lumbosacral injuries, we need a different kind of cell therapy, i.e. neural stem cells that can replace neurons. We are working hard on establishing a cell source for neural stem cells. At the present, there are only three sources of neural stem cells. First, embryonic stem cells can be differentiated into neural stem cells. Second, fetal neural stem cells can be obtained from aborted fetuses. Third, adult neural stem cells can be obtained from a person's brain. The first two sources are not immune-compatible. While the last is immune-compatible (if obtained from the brain of the person), it is difficult to jsutify removing part of the brain to treat the spinal cord. By the way, while a number of groups have reported success in making neural stem cells from bone marrow or mesenchymal stem cells, these have not been particularly reproducible nor have the studies provided credible evidence of beneficial effects of such cells in animal spinal cord injury models.

Fortunately, a new option has recently been made available for creating immune-compatible neural stem cells without having to take out a chunk of one's brain. These are induced pluripotent stem (IPS) cells. By insertion of four genes into skin cells (fibroblasts), several groups have shown that it is possible to create embryonic stem cell like pluripotent cells. Unfortunately, much work still needs to be done to ensure the safety of such cells because they have a propensity to grow into tumors when transplanted. We and many other groups are working hard testing IPS cells in animal models and figuring out how to make IPS cells safer. I believe that IPS cells will become available for clinical trials in about 3 years.

Finally, what about other kinds of spinal cord injuries, such as those resulting from ischemia (loss of blood flow) or transverse myelitis (probably inflammation mediated)? I believe that these should not be tested together with traumatic spinal cord injury because both the causes and response of these injuries to umbilical cord blood mononuclear cells and lithium may be different. The best way is to carry out a separate phase 2 trial on people with ischemic and transverse myelitis. Such a trial would be open label and intended to establish safety and feasibility of the cell transplant and lithium therapy for transverse myelitis. Such a clinical trial could be done with about 20 people.

Wise.

dear dr. young,
it would bring a lot of hope to most of us to see the videos of people walking, about which you are talking about.
please reconsider.
thanks
gautam

[PLS]

Dr Young
I am a C4/5 quad and would pay almost anything just to improve to a C5/6 level. The difference in functionality, independence, posture and comfort in the wheelchair is profound between these levels. It would relieve so much pressure on my wife.
Is there any chance that this procedure could produce, not cure, but improvement?

PLS

[Chaz19]

Chaz19,

I listened in to this webinar and then downloaded this pdf. It's a lot of information all at once, but it answered questions I didn't even know I had. I think this is so helpful, and this way Dr. Young doesn't have to repeat himself again and again.

Here's the webinar.
http://www.thisabled.com/stem-cell-webinar.php


Here's the pdf slideshow that went with it, updated, so they can be seen well.
http://www.thisabled.com/StemCellWebinar.pdf

I think that would answer your request for layman's history and for updated info on stem cell trials.

--Flame carcanet

Flame-
This is great. Thanks. Is there a way to have these links as a sticky?

Dr. Young- I understand what your saying about a video. It is a fuzzy line between providing information to the public and marketing/creating a fundraising medium for experimental trial. I highly respect the direction of http://www.justadollarplease.org/. I'll direct people who are interested to that site.

[Jim]

Done Chaz, here's the new thread- /forum/showthread.php?p=1064052#post1064052

[Jim]

If you want to take part in the SCINetUSA eNewsletter Fundraising Campaign, send me your info- jimbenn@rci.rutgers.edu.

[Leo]

Hey All,

I bounced this idea off Jim and am waiting to hear back.

i was looking into the cost of a 2' by 6' vinyl banner made of the dollar a day logo thing

it will run just under 40 dollars, if we order 4

my thought is here where i live we have a yearly celebration like most towns do, thousands of people come

so i plan to strategically place it where many will see it, and watch the money roll in.....we hope

when our event is over i would be happy to send it to someone else who's got some thing going and yada yada

your thoughts?

[Jim]

Great idea Leo!

Re-using the banners for a bunch of events is perfect.
We should get 4-6 made.

When people have fundraisers, please take pictures so we can put them on the http://JustADollarPlease.org website!

Anything I can do, let me know

[Leo]

Any other takers on a banner or investing 40 to by one so we can have these available?

Contact me

Great idea Leo!

Re-using the banners for a bunch of events is perfect.
We should get 4-6 made.

When people have fundraisers, please take pictures so we can put them on the http://JustADollarPlease.org website!

Anything I can do, let me know

[Sue Pendleton]

Do you mean like county fairs or Maxwell Street Days? Do these venues require a permit of any kind or can a 4-H chapter/township hang it in their area?

[Leo]

Permits! Permits!...we don't need no stinking Permits

Hi Sue,

I'm sure all those places may need an ok from someone or

you could go by the rule of ask for forgivness after the fact

heres our event http://www.riverboatdays.com/ shameless plug. check out the band Dweebs, these folks are great singers entertainers and can play every thing and maybe from Wisconsin.


Hey Jim, can you get me that logo in vector format and PDF?

We've had 3 people chip in so far.

laters

[Jim]

Working on it Leo

[Jim]

Leo,

When I convert it the images become distorted. I emailed a friend who is a graphic artist. I'll let you know.

Jim