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Thread: Chronic Studies

  1. #31
    I understand what you're saying BigB...If all they were pushing for were for chronic SCI, it might look bad. But I wouldn't think it would look bad to split it equally, would you? I agree we all need to speak up about our concerns to researchers and the foundations that are funding the research. Ask them questions, put pressure on them. Let them know we're here and we want help sometime in our lifetime. Christopher Reeve does his share of that! But he is just one person.

  2. #32
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    Schmeky,

    Wise posted this comment on another thread on CC (5/29/04)...he did not whisper it in my ear at Rutgers: [His comment was in response to my question regarding chronic studies.]

    "cmaus, there will be studies. Keep your ears to the ground. I believe that there will be many studies presented at the upcoming Society for Neuroscience and Neurotrauma Society. Wise."

    Thx,
    Sue

  3. #33
    CSMAUS1, So even if there are a few studies that may be going on for chronics what would be wrong if there were more. Are you saying enough is being done? You seem to be trying to calm us down, why?

  4. #34
    Senior Member alan's Avatar
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    Originally posted by BigB:

    To me this is scary. If they can cure an acute who says they will continue to do the work to help the chronics, as time goes on there will be less and less chronics if they can cure acutes.
    Look at polio. They developed a vaccine to prevent new cases (acutes), but has anyone who had polio been cured? Not to my knowledge.

    Alan

    "Was it over when the Germans bombed Pearl Harbor?"

  5. #35
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    BigB,
    First of all, my response was related to the "whispering" comment--I wanted it to be clear that Wise posted the comment on CC for all to read.

    Of course, considering I have a c4/c5 spinal cord injury nearly 4 years post, enough will never be enough until all are cured. I'm not trying to calm anyone down, either, I was just explaining earlier what it takes to create a chronically injured rat model and why there might be more acute experiments vs chronic. That doesn't mean none or very few are being done--I'm keeping my ear to the ground.

    Thx,
    Sue

  6. #36
    Bigbob,

    Only a handful of laboratories can do chronic animal spinal cord injury experiments. There are several reasons for this:

    1. Difficulty of caring for animals with chronic spinal cord injury. It takes very skilled and experienced full-time animal caretaker to care for animals with spinal cord injury. Most laboratories do not have enough of such people to do chronic spinal cord injury therapy studies. Also, it is very difficult to re-expose the spinal cord injury site in a rat. Until recently, we could not do so because adhesions of the dura to the laminectomy scar were so tight that it was difficult to re-expose the spinal cord injury site without damaging the spinal cord further. We recently solved this problem by finding a biomaterial that prevented the scarring.

    2. Time. Chronic spinal cord injury experiments take a long time. If we assume that every week in a rat is equal to a month in human time and we define 12 weeks as "chronic", this means that it may take a laboratory 3 months to create a large population of such rats. Let us suppose that it takes another 3 months to demonstrate regeneration and locomotor recovery. Suppose further that the experiments are comparing three treatment groups and a control group, e.g. cell transplant alone, cell transplant plus some kind of growth factor, the growth factor alone, and a control (untreated group). Finally, let us assume that the experiment has a 10-12% mortality rate (that is very good, by the way). Thus, in order to ensure that you have 12 rats per treatment group, you need to injure at least 15 rats are required per treatment group, adding up to 66 rats. Even if one injured 6 rats per week, it will taken 11 weeks to get all the rats injured. Suppose that a second operation will have to be carried out on the rats at 12 weeks after injury. After the experiments are complete, it takes a 2-person team several days to prepare and examine all the microscope slides from one rat. So, in total, such a chronic spinal cord injury treatment experiment would requires a team of about 4 people working full-time for about year.

    3. Funding. Let me give you an idea of the costs of a chronic spinal cord injury experiment. A team of 2 fulltime technicians and 2 investigators will cost about $200,000 per year. If cell transplantation is involved, the laboratory must have people and equipment to do cell cultures; add another $20,000. The cells must come from other rats or sources. The cost of maintaining rats, drugs, surgical supplies, and the cells for transplantation add up to about $500 per rat over a 6 month period. For 66 rats, this adds up to another $30,000. This comes to about $250,000 direct costs for one chronic spinal cord injury treatment experiment. By the way, institution indirect costs are typically 60% of direct costs. Therefore, one would have to raise $400,000 in research grants to fund such a study.

    When she visited the lab, I explained to Sue (cmaus1) what is entailed in taking care of a colony of spinal-injured rats. Starting from the day of injury, you have to squeeze their bladders at least once and often twice a day. By the way, expressing the bladder manually is something that only very skilled and experienced technicians can do. Suppose that it takes 5 minutes to express the bladder of one rat. That means that one technician can only 12 rats per hour. It would take 6 hours to squeeze the bladders of 66 rats and then it is time to check them again. Of course, this must be done 7 days a week. You need at least two full-time animal care technicians to care for a colony of 60 rats.

    An acute spinal cord injury experiment would take only half the time and therefore cost. In other words, a laboratory would be able to do twice the number of experiments. Since few laboratories have the people, the time, or the funding to do chronic spinal cord injury experiments, it is not done as often.

    Until recently, most investigators believed that the best hope for therapies is to apply them soon after injury. However, many laboratories have reported that cell transplants do not work as well if the cells were implanted into the spinal cord immediately after injury. The environment of the injured spinal cord appears to be deleterious to survival of cells. Many laboratories have shown that transplanting the cells at 1-2 weeks allow more survival of the cells. I think that this may be the reason why the Bunge study transplanted the Schwann cells into the spinal cord at 1 week after injury.

    Finally, let me describe the funding of spinal cord injury experiments. Traditionally, most research grants come from NIH. At the present, NIh grants typically provide between $200,000-$300,000 of direct cost. This is not enough to cover the expenses of doing one series of chronic spinal cord injury experiments. So, most investigators stretch out the experiments over more than a year. In the meanwhile, however, NIH grants require proof of productivity (i.e. publications) before they are refunded. So, most investigators know that they must produce 2-3 papers per year in order to get refunded. So, what do investigators do? They do more acute spinal cord injury experiments than chronic spinal cord injury experiments. Oh, and I forgot to mention that this year only about 12% of research grant applications were funded by NIH. So, investigators (such as myself) have to spend about half of our time seeking funds to support our teams so that they can do the experiments.

    Wise.

    [This message was edited by Wise Young on 06-19-04 at 08:54 PM.]

  7. #37
    Senior Member gettinup's Avatar
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    Dr. Young,

    What are the chances that acute SCI research that results in cure will assist chronic?

    Also, when does acute end and chronic begin?

    Also, what has been the affect of the internet on life science research?

  8. #38
    Thanks Wise
    Although the experiment would take twice as long, wouldn't the only cost differential be the maintaining of the rats, which would mean the actual cost would not be twice as much.I'm sure the investigators could work on another experiment while they are waiting for the rats to achieve chronic stage. If thats the case it could be worked out. As far a the papers or reports you say are needed(So, most investigators know that they must produce 2-3 papers per year. So, what do they do? They do acute spinal cord injury experiments.) Is there anyway around that?

  9. #39
    Bigbob,

    Say that you have a research team consisting of one principal investigators, a postdoctoral fellow, and two technicians, being funded by an NIH grant of $250,000 per year direct cost. To achieve 3 published studies per year, the team can do either:
    • Two acute spinal cord injury experiments per year and one chronic spinal cord injury study stretched out over two years, or
    • One chronic spinal cord injury experiment per year.

    Not Enough Spinal Cord Injury Laboratories. About 7 years ago, I became very concerned about the problem of not enough laboratories having the capability of doing chronic spinal cord injury studies. In 1997, I estimated that there were perhaps 30 laboratories around the world that was able to do spinal cord injury experiments. To address the three problems that I outlined below, we started a quarterly spinal cord injury workshop where we stop everything that we do in the lab and teach other laboratories how to do rat spinal cord injury, care for spinal-injured rats, and do chronic spinal cord injury studies. Over the last six years, we have trained over 250 investigators to do spinal cord injury research.

    Surrogate Measures. There is one way to reduce the time required for chronic spinal cord injury experiments. We have been trying to develop gene expression measures that could provide surrogate measures of regeneration. Using gene chips, we identified several families of genes that are expressed when the spinal cord is regenerating. Dr. Ron Hart in our Center spearheaded these studies with a graduate student, Jason Carmel. To do these studies, we invested about $2 million into equipment and studies to optimize the gene chips, and providing the service to collaborating laboratories at a tenth of the cost of commercial gene chips. I believe that these surrogate measures will allow investigators to test different doses of drugs and other therapies without having to wait months for regeneration to happen and recovery of walking in the rats.

    Inadequate funding. The way to getting more chronic spinal cord injury experiments is of course to get more funding of spinal cord injury research. One of the most unfortunate misconceptions that the spinal cord injury community has is that scientists are flush with money. Please this is not so. I worked with Arthur Ullian in the mid-1990's to lobby Congress to double NIH funds. NIH funding did double but I don't think that spinal cord injury research funding doubled. I estimate that NIH is currently funding $68 million per year of SCI research compared to $48 million in 1995. The Quest for Cure group has been remarkably successful in getting state funding for spinal cord injury research, funding perhaps $20-$30 million per year. So, today, despite the low level of NIH funding today (only 12% of research grant applications), many spinal cord injury laboratories are continuing to do their work. By the way, just for comparison, foundations provide only a small fraction of spinal cord injury research funds, probably no more than $10 million per year.

    Gettinup, More and more laboratories are beginning to do chronic spinal cord injury experiments and we should be hearing more of these this coming fall. Therapies that regenerate the acutely injured spinal cord should also be beneficial for chronic spinal cord injury. My personal definition of "chronic" is when a person or animal reaches a recovery plateau. This is usually at 6-12 months in most people. This doesn't mean that the person will not recover more function beyond 12 months but the rate of recovery is much slower. In the rat, I would say that 6-12 weeks is "chronic".

    Regarding Internet large impact on science, the greatest effect has been in communication. Instead of telephone and faxes, we can now exchange data and information faster than ever before. Email discussions between scientists are common. Almost all journal submissions and reviews are now being done over Internet. One other important effect has been the availability of journal abstracts from Medline. We use to have to send hard copy reprints around. The availability of pdf copies of articles has allowed people to read, write, and disseminate research results very quickly. Finally, collaborations between laboratories are much easier with Internet, reducing the isolation of laboratories from each other.

    Wise.

  10. #40
    When chronic and acute studies are referred to I take that to mean that they are trying to find a treatment to return the spinal cord to function below the injury which would mean a great return. What I would like to know is if and how many studies are being done that can return a more specific function such as getting someone off a vent, or to return grip or bowel and bladder function. Also are these the kinds of studies that would fall under chronic studies or are they in a class by themselves?

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