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Thread: McMaster scientists regenerate spinal cord - Revolutionary new technique uses intestinal cells

  1. #11

    Vicar

    I can't really speak for these investigators. Traditionally, when one is testing drugs, the FDA requires safety tests in one large animal species and one small animal species. Dog experiments fulfil the former requirement. On the other hand, I don't think that this applies to cell autografts. I don't think that this is necessarily even something that should be tested in primates. There is no serious safety question here with an autograft, as opposed to other treatments such as IN-1, genetically modified cells, porcine cells... where there are safety and rejection issues. I personally think that this is something that probably can pass muster with an IRB for a phase 1 clinical trial. I would also want to study the publication of the work to be convinced that the results are as glowing as the newspaper report suggests that it is. If the results are not that strong or the study is flawed, the route is to have another laboratory replicate the study. After that point, the rationale for going to clinical trial is probably no more or less than the rationale that was used to justify the phase 1 trial on activated macrophages.

    Wise.

  2. #12
    Senior Member rdf's Avatar
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    That makes a lot of sense, Wise. Newspapers and researchers always paint a rosy picture, and the actual facts are needed to judge how important this is. I would love for it to be that one magic therapy that does it all.
    About replicating a therapy, don't you think that the reason Dr. Cheng's therapy hasn't been reproduced might be because he hasn't told everybody everything? I wonder how much information Dr. Rathbone is willing to release.

  3. #13

    Just curious Dr. Young

    If someone had the money, how hard would it be to get a Dr. and IRB approval to try this procedure in the US? Isn't it possible to get something like this done without a formal FDA study and approval?

  4. #14

    Carl R and rdf

    Carl R, it is not advisable for anybody to do an therapy that is as radical and experimental as this one without Institutional Review Board (IRB) approval in a hospital. IRB is necessary to ensure that consent is informed and the doctors that apply the experimental therapy are protected legally. Note that neither are truly protected in the sense that patients sometimes will get injured as a result of the experimental therapy and the doctors still can be sued for negligence (as illustrated clearly by the Jesse Gelsinger case). The key requirement is "informed consent". The subject of the experiment must know and understand all the risks and the investigator must perform the procedures as specified.

    rdf, Dr. Cheng cannot be blamed for not sharing the details of a therapy and the results of a trial while it is still ongoing. I have not yet seen the paper from Dr. Rathbone (by the way, the studies are just coming out faster than I have time to read them). I suspect that the paper will provide all the details of the therapy. I don't think that the problem is withholding the data as much as the fact that there are relatively few laboratories today that are set up to do transplant experiments in a well-documented spinal cord injury model. Most of the laboratories that are doing such studies (such as ours) are already committed to the limits of our resources in terms of doing other studies and may not be able to switch over to a new cell type without several months of preparation. Also, it take time to obtain funding for new studies (from NIH, it takes about 3 months to write a grant for one of three submission dates and about 9 months for the NIH to review and award the grant).

    This is one of the reasons why our Center has put a great deal of effort into training as many laboratories as possible so that there is a critical mass of laboratories that can jump on these opportunities as soon as possible. Much of the delay in getting therapies to clinical trial stems from the long lag time in getting replications of results. Note that while a phase 1 type trial (to determine safety and feasibility) may go ahead with minimal safety data, progression of the trials to phase 2 or 3 will require hard animal data indicating the best dose, timing, and method of transplantation of this cell type, to increase the likelihood that the trial will succeed. Because this particular therapy will require the removal of a segment of the intestine (presumably this is how they got the cells), harvesting, and isolation of the intestinal glial cells, it will not be a trivial operation.

    Wise.

  5. #15
    i saw on eds pictures that dr.kao is using the intestines also during his surgery,is that kinda like this?by how dr.kao is using them what will that help as far as recovery?thanks jeff

  6. #16

    jeff

    what an astute observation! When Harry Goldsmith first started doing omentum transplants to the spinal cord, many of us in the scientific community were fascinated by the possibility of intestinal omental cells and growth factors interacting with the spinal cord. The omentum is an incredible structure. It is one of the most active vascular tissues in the body. The omentum vascularizes the guts and carries virtually all the nutrients that we ingest. Within 24 hours after a pedicled omentum graft is placed on the spinal cord, the omentum is sending blood vessels into the spinal cord, along presumably with its attendant cells and growth factors. The gut is constantly renewing itself and the omentum likewise has to respond rapidly to changes of the gut. There is an important story here but unfortunately it has not been well-investigated and remains outside of the mainstream of the spinal cord injury field. I was fascinated by Dr. Kao's adoption of the omentum graft as a means of preventing scar formation after the surgery. This is quite an interesting and innovative idea and one that is worthy of attention by the scientific and clinical community.

    Wise.

    [This message was edited by Wise Young on August 18, 2001 at 08:40 AM.]

  7. #17

    Another article about the research being done at McMaster U

    http://www.nationalpost.com/home/sto...16/648139.html

    Canadian researchers have been able to rebuild nerves in rats by injecting the spinal cord with cells from the intestine


    Tom Arnold
    National Post
    A Canadian laboratory has discovered that nerves can regenerate in the spine when cells from the intestine are transplanted into a severed spinal cord.

    The McMaster University finding is being touted as a major breakthrough in spinal-cord injury research, potentially bringing new hope to 40,000 paraplegics and quadriplegics across the country.

    "It is very dramatic," lead researcher Michel Rathbone, a professor of medicine at the university in Hamilton, Ont., said of the findings. "The important advance is that we've shown that nerves that normally do not regenerate at all can be made to regenerate with the body's own cells.

    "Obviously, this has the potential to be a cure, but just as it took 60 years from the first airplane flight to get to a 747 airliner, it is a giant leap." Rathbone will present the results at a Society for Neuroscience meeting in San Diego, Calif., in November.

    With spinal injuries, it is commonly thought the nerve cells are destroyed. They are not. It is the cell processes, or the long, telephone-like wires that run throughout the spinal cord, that are damaged, prompting the permanent injury. This research has the potential to reverse the damage.

    In experiments with rats, the scientists extracted enteric glia cells from the intestine, purified them, and then injected the cells into the spinal cord, where sensory nerves enter. Soon, the enteric glia began migrating, prompting the nerve fibres to follow suit, returning to normal growth.

    "This means we can now make nerve fibres regenerate through the spinal cord, which normally they would not do," said Rathbone. "Every single one with enteric glia showed a very robust growth of cells into the spinal cord. This is not just a little bit significant because this doesn't happen normally. It just does not happen."

    Rathbone pointed out there are many advantages to working with enteric glia cells, which do everything from controlling interconnections between nerve cells to covering axons, the part of the nerve cell that delivers impulses from cells to muscles. The advantages include little likelihood of rejection by the body because the transplanted cells are from the same person.

    About 50 rats were used for the research. The 40 animals that were control groups showed no response, while all 12 rats injected with enteric glia demonstrated the regeneration.

    For humans, the scientific possibilities are immense. If the technique were able to regenerate the spinal cord just two or three centimetres, said Rathbone, arm and hand movements would return. "That would turn a quadriplegic into a paraplegic and totally change their quality of life.

    "A person who is quadriplegic may not be able to feed themselves but if you could give them back movement of the hands, they can do many, many things," he said.

    The Canadian Spinal Research Organization, a group of paraplegics and quadriplegics whose goal is to find a cure for spinal injuries, has given more than $1-million to Rathbone's laboratory in the past eight years.

    "I think these findings are significant," said Ray Wickson, the group's president. "It's proving in the animal model to be successful and I can see, not tomorrow but in a few years if everything progresses the way it is going, it being used in human clinical trials."

    Wickson first heard about enteric glia cell research in the late 1980s. Convinced it might one day pave the way to a cure, Wickson approached Rathbone to begin laboratory testing.

    Among those who could be affected by Rathbone's research is U.S. actor Christopher Reeve. The actor, best known for his high-flying role of Superman, became a quadriplegic after he was paralyzed in a fall from a horse.

    Reeve, who is an outspoken advocate of cutting-edge spinal research, including studying embryonic stem cells, broke his neck in the May, 1995, accident. He has the most severe spinal-cord injury the human body can endure, leaving him without use of his arms or legs, bladder or bowel control or sexual function. He can breathe on his own only for short periods of time.

    "The promise of human trials is obviously down the road but it holds out exciting future potential," said Stephen Little, a spokesman for the Canadian Paraplegic Association. "They still have a lot of challenges but anything that could help reduce the impact of spinal-cord injuries, whether it's some kind of sensory gain or motor function gain, is just that, a big gain."

    In the future, Rathbone intends to observe animals with spinal damage over a longer period of time to see whether they also produce the same regenerating result with the injection of enteric glia cells. He also hopes to begin work on larger animals, including dogs. If all goes as planned, he believes human trials will be underway within three years.

  8. #18

    Dr. Harry Goldsmith

    Harry Goldsmith, M.D.:
    Hope for Spinal Cord Injuries


    Dr. Goldsmith is a surgeon who has developed a most remarkable procedure for spinal cord injuries, Alzheimer's disease, stroke, and other neurological disorder.

    During this procedure, called omental transposition, the omentum, a nutrient-rich fatty apron covering the intestines, is laid over an injured spinal cord or brain -- with dramatic results. In the June, 1997 issue it was reported how this procedure transformed Darren Renna, who became paralyzed in a gymnastics accident and was so disabled he had to be strapped into a wheelchair. After having this procedure, he had a remarkable return of function. He is able to write and maneuver his wheelchair, and has a career as a gymnastics judge.

    Yet this procedure, which is routinely used in China and South America for cerebral palsy, Alzheimer's disease, and spinal cord injury, is inexplicably ignored in this country by neurologists and surgeons, whose patients would benefit enormously.

    For more information on omental transposition, write to Dr. Goldsmith at P.O. Box 493, Glenbrook, NV 89413 or fax 702-749-5861.
    ***************References***************

    Goldsmith HS, et al. 1999. Omental transposition for
    cerebral infarction: a 13-year follow-up study.
    Surg Neurol 51:342.

    Goldsmith HS. 1997. Omental transposition to the brain
    for Alzheimer's disease. Ann NY Acad Sci 826:323.

    Goldsmith HS. 1996. Omental transposition for
    Alzheimer's disease. Neurol Res 18:103.

    Goldsmith HS. 1994. Brain and spinal cord revascular-
    ization by omental transposition. Neurol Res 16:159.

    Goldsmith HS, et al. 1992. Axonal regeneration after
    spinal cord transection and reconstruction. Brian
    Res 589:217.

    Goldsmith HS. 1990. [Lack of atherosclerosis in
    omental arteries]. Lancet 335(8686):409.

    Goldsmith HS, et al. 1990. Regional cerebral blood
    flow after omental transposition to the ischaemic
    brain in man. A five year follow-up study. Acta
    Neurochir (Wien) 106:145.

    Goldsmith HS, et al. 1986. Increased vascular perfusion
    after administration of an omental lipid fraction.
    Surg Gynecol Obstet 162:579.

    Goldsmith HS. 1980. Salvage of end stage ischemic
    extremities by intact omentum. Surgery 88:732.

    [This message was edited by Birde on August 18, 2001 at 12:38 PM.]

  9. #19
    An interesting link: http://www.csro.com/ENTNEU.HTM

    Dr. Young, would it affect the food digesting process, if those cells are taken? Or is there too little amount needed?


    Dr.Michel P. Rathbone
    Enteric Neuron and Glia Transplantation into Spinal Cord


    --------------------------------------------------------------------------------

    Fact can be stranger than fiction - fish skin and intestines may each help in spinal cord injuries. Your mother likely told you that eating fish was good for your brains - now a group of researchers at McMaster University funded by the CSRO are finding that it may be good for injured spinal cords, too. The substances which make fish skin shiny are called purines (pronounced "pwe-er-eens"). These purines help in fish development and in spawning. Purines are also found inside all cells as building blocks of DNA and RNA, the genetic material. As well, purines are the energy currency of cells. But purines have very important roles outside cells, too. There are also chemical messengers, purines released by one cell move in the fluid outside cells taking information to other nearby cells. So, for example, purines are one of the chemicals which transmit messages from one nerve cell to another.

    Substances from fish skin may help protect the spinal cord immediately after injury: Over the last few years work from several laboratories, particularly from Dr. Rathbone's laboratory at McMaster University, has shown that purines outside cells play important roles in spinal cord and brain injury. When cells in the nervous system are damaged they release large quantities of purines. Purines help protect cells from further damage. As well, purines carry special messages to cells surrounding the damaged area. This makes them release "trophic" substances which help repair nerves in the brain and spinal cord.

    Unfortunately, in most cases not enough purines are released and substantial damage results. In research funded by the CSRO, Dr. Rathbone and his colleagues have tried to increase the purine levels after spinal cord injury (SCI). They found that when the synthetic purine 4-{[3-(1,6dihydro-6-oxo-9-purin-9-yl)-1-oxypropyl]amino} benzoic acid, also called leteprinim potassium, is given following SCI, the effects of the injury are minimized. Currently they are attempting to find how exactly this substance improves the outcome of SCI. "We are attempting to boost the naturally occurring protective and repair processes in the spinal cord, said Dr. Rathbone. "We are using a modified purine which is even more effective than those found in fish skin and in the nervous system".

    One of the types of cells which the purines affect are known as glia. Glia are supporting cells in the nervous system. There are several types of glia. One type, astrocytes, has many functions. Astrocytes form the scars in the nervous system after injury. But astrocytes can also make the protein trophic factors which help the nervous system to recover after injury. Purines make astrocytes synthesize and release more trophic factors. Rathbone and his colleagues think that astrocytes and another type of glia, microglia or scavenger cells, are important in helping the purines to reduce the effects of spinal cord injury.

    Cells from the intestine may help regeneration of nerves in the damaged spinal cord. The problem of repairing the injured spinal cord long after it has been injured is a different problem, but one that nevertheless also may involve glia. After the spinal cord is injured a very complicated series of processes occurs involving nerve cells and several types of glia. The overall result of these is to prevent regrowth of nerve cell processes across the region of damage. However, recently glia from the nerves at the back of the nose have been transplanted into the spinal cord. The glia from the nose then migrate, literally crawling up and down the spinal cord. In doing so they seem to make paths for regenerating nerve cell processes to follow, as though they are towing the nerve processes along. But there are not many glia in the nose, so the use of this technique in human SCI is potentially limited.

    Rathbone and his colleagues, funded by the CSRO, have taken another approach. The intestine has a nervous system which makes the gut move food along it. The intestinal nervous system contains glia which are similar to astrocytes. Pamela Middlemiss and Shucui Jiang, working with Dr. Rathbone, isolated and purified the glia cells from the intestine of rats. They then added a substance to mark them and were recognizable from the staining. Now these researchers are trying to determine whether these glia from the gut will release trophic factors which make the nerve cell processes grow as do the glia from the nose.

  10. #20
    dimitriy, I don't think that removal of a segment of the intestines (or whatever they did to remove the "intestinal glial cells") would necessary compromise the function of the intestines in the long run. We have more intestine (22 feet of it, for that matter) than we must have). However, as I pointed out, the surgery itself is not trivial and it can have complications. Wise.

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