A question for wise

[lunasicc42]

how is the timeline looking for starting the higher trials in the US? I say that also because I believe that if it works at C5 and down, it will work at C4... Have you ever tested it in a C4 rat? If so, what happened ?

Also how about people with syrinxes? I have a syrinx that was shunted

I say this because as soon as the trials accept my level of injury, I will be there.

So the main question is when will timeline for safety to be established so the trial can move to higher injuries? And whats the word on syrinxes

[ineedmyelin]

Originally Posted by lunasicc42

how is the timeline looking for starting the higher trials in the US? I say that also because I believe that if it works at C5 and down, it will work at C4... Have you ever tested it in a C4 rat? If so, what happened ?

Also how about people with syrinxes? I have a syrinx that was shunted

I say this because as soon as the trials accept my level of injury, I will be there.

So the main question is when will timeline for safety to be established so the trial can move to higher injuries? And whats the word on syrinxes

Quit reading my mind, lol. My injury is also at c4-c5 and yep i also have a beautiful syrinxe.

[lunasicc42]

http://www.youtube.com/watch?v=Xg2vMrDzoXM

This is my theme song for when trials get going for my type of injury... Because "I'll be there "

[BSgimp]

Why do you wanna throw yourself into this without the proof that it actually work. Just wait for initial report from trials in China. And dont get your hopes up. The disappointment wont hurt as bad. Saying this from experience of countless disappointments.

Its like science. You can come out with theory but without documented, legitimate proof your theory is just a concept. In this case without documented results from China trials this therapy is useless.

[lunasicc42]

Wise, please tell me the deal for higher injuries and a syrinx

[Wise Young]

Originally Posted by lunasicc42

how is the timeline looking for starting the higher trials in the US? I say that also because I believe that if it works at C5 and down, it will work at C4... Have you ever tested it in a C4 rat? If so, what happened ?

Also how about people with syrinxes? I have a syrinx that was shunted

I say this because as soon as the trials accept my level of injury, I will be there.

So the main question is when will timeline for safety to be established so the trial can move to higher injuries? And whats the word on syrinxes

Lunasicc42,

Let me explain the rationale behind the staging of the clinical trials. The purpose of clinical trials is to establish the risk-to-benefit ratio of experimental therapies. If the risk of a therapy is low, i.e. there is no harm in the therapy, you don't need a lot of justification to do the trial. For example, if you want to know whether taking a vitamin a day (a very low risk activity) improves recovery in chronic spinal cord injury, you don't have to get do any safety or animal studies to take that treatment to clinical trial in the United States or any other country in the world.

If the therapy involves surgery, which has well-established and known risks, one needs to show that the therapy has some benefit in animals to warrant putting patients to risk. However, since the risk of surgery is relatively low, one doesn't need to have a great deal of efficacy data to justify a trial. If the therapy involves transplantation of cells, which has both known and unknown risks, one needs to define the risk of the therapy in animals before it can be tested in humans.

Defining risk does not necessarily mean eliminating risk. For example, Geron proposed a trial that involved not only surgery but transplantation of a cell that is known to cause tumors called teratomas in animals. Therefore, the FDA required them to define the risk of teratoma formation in small animals (usually rodents) and at least one large animal species. The FDA ultimately required Geron to differentiate their human embryonic stem cell to the point that less than 1 out of billion cells are pluripotent. This reduced but did not eliminate the risk.

In our case of umbilical cord blood mononuclear cells (UCBMC), these cells have been infused intravenously into over 30,000 patients in the past 25 years with no report of tumor formation. It is true that laminectomy (removing the bone on the back of the spine) and durotomy (cutting open the dura) entails some risk but this risk is well known and small. So, we are required to show that the cell transplants have some benefit in animal studies. Indeed, well over a dozen independent laboratories have reported that umbilical cord blood cells improve functional recovery in both small (rat) and large (dog) animal models of spinal cord injury.

However, we do not know what is the safest and best volume of cells to inject into the spinal cord. In China, they typically inject 35 µliters of olfactory ensheathing (usually 100,000 cells/µliter) into the central part of the spinal cord. In the Geron and the Stem Cell Inc. trial, I believe that they were injecting 50 µliters of cells into the spinal cord below the injury site. They usually inject this amount into the middle or below the spinal cord. We wanted to inject cells into the spinal cord just above and below the injury site by inserting the needle at a 45˚ angle into the dorsal root entry zones.

Note that 1 microliter (µliter) is equal to 1 cubic mm of volume. A 50 µliter sphere would have a diameter of 4.57 mm. The diameter of the human thoracic spinal cord is about 15 mm. So, a 50 µliter sphere of cells would be nearly a third the diameter of the spinal cord. We had also shown that a bolus injection of 30 mg/kg methylprednisolone (MP) improves survival of the injected cells. Finally, we showed that giving lithium causes the injected umbilical cord blood cells to proliferate. Therefore, we designed a phase 2 trial to compare five treatment groups: four injections of 4-, 8-, and 16-µliters in the first three groups, then the highest safe dose of transplant plus MP, and the transplants with MP and a 6-week course of oral lithium.

Our phase 2 trial must show that transplant procedure is safe, i.e. does not cause any loss of function before we can proceed to phase 3. Note that the phase 2 trial does not have enough patients to prove the the treatment is effective. We need about 20 patients per treatment group to detect a credible 10% difference in recovery (p<0.05). Our phase 2 trial would not be enough to detect statistically signifiant changes of recovery but it would show safety and trends for efficacy. If so, we would go to the phase 3 trial with larger numbers of subjects to establish the efficacy of the treatment.

In our trials to date, we limited the neurological levels to C5 or lower. This is because the phrenic nucleus (the nucleus in the spinal cord that controls breathing) is situated at C3 and C4 spinal cord. Because we are injecting the cells above and below the injury site, a person with a C5 neurological level (i.e. C4 must be intact) the cells would be injected into C4 spinal cord. We do not want to do so unless we know that the procedure has safe and has sufficient beneficial effects to warrant the risk.

So far, our results in the phase 2 trial have been reassurring in terms of safety. We have been looking for adverse events associated with the cell transplants. None of the patients have shown any significant neurological loss from the injection of cells above the injury site. One patient had an increase in pre-existing neuropathic pain associated with sensory return in dermatomes below the injury site. Although it is too early to tell, many of the patients are getting some sensory function and a few are getting some motor function.

We are waiting for all the 6-month followup before using the data to apply for the U.S. trials. We are still raising funds for the phase 2 trial to start in Brackenridge in Q4 2012, to show the safety and feasibility of intensive locomotor rehabilitation. We are aiming to start the phase 3 trial in mid-2013 in China, U.S., Norway, and India. Because we won’t get credible efficacy data until 2014, It is unlikely that we will start a phase 2 on upper cervical spinal cord injuries before 2014.

Regarding syrinxes, we have been excluding patients who have syrinxes that are wider than a third of the diameter of the spinal cord. The reason is because we do not want to transplant the cells into the syrinx, where they will be isolated from the spinal cord. The decision to accept patients for the trials are made the surgeons and rehabilitation doctors running the trials in each center. Surgeons must decide whether they can safely inject the cells into the spinal cord above and below the injury site. Rehabilitation doctors must decide whether the subjects can tolerate the planned locomotor training procedures.

Wise.

[lunasicc42]

so: in short: approx... 2014

And if the Syrinx is bad, well it's up to the investigator

[ineedmyelin]

Originally Posted by lunasicc42

so: In short: Approx... 2014

and if the syrinx is bad, well it's up to the investigator

bummer!

[lakboy]

so now we are already talking about 2014 , give it another two years and that makes it 2016-2017 , sounds very familiar 5 years !

[Wise Young]

Originally Posted by lunasicc42

so: in short: approx... 2014

And if the Syrinx is bad, well it's up to the investigator

Lunasicc42,

Once the therapy is approved, it will be up to the doctors anyway whether or not it should be applied at different spinal levels. The phase 2 trial may not be necessary to convince doctors to do a trial first. Much depends on the resultz. Likewise, if you have a large syrinx, it should be fixed first or at least at the time of transplant. I hope that your syrinx is less than a third of the diameter of your cord.

Wise.