Announcement

Collapse
No announcement yet.

Comments on embryonic stem cell research and Alzheimer's disease

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

    Comments on embryonic stem cell research and Alzheimer's disease

    Many people have recently written to me because they were concerned by an article by Rick Weiss of the Washington Post entitled Stem cells unlikely cure for Alzheimer's, suggesting that the Nancy Reagan's hope that embryonic stem cells will cure Alzheimer's Disease has been misplaced. Prolife writers such as Wesley Smith in "Of Stem Cells and Fairy Tales" claimed that " Scientists who have been telling Nancy Reagan that embryonic stem cell research could cure Alzheimer's now admit that it isn't true." I have written a rebuttal of that particular article] but am concerned about the unwarranted bashing of scientists and the injection of doubt about the value of embryonic stem cell research. Many additional articles have appeared in the last several days echoing the doubt. For example, NewsMax.com has an article called "Stem Cells Not the Priority for Alzheimer's", Malcom Ritter of AP has an article named "Other approaches likely to trump stem cells in Alzheimer's research", and Ann Harding for The Scientist wrote "Stem cells for Alzheimer's" stating that the approach is "unlikely to yield cure for the disease, experts say, although some look to endogenous stem cell manipulation". Several scientists that I respect and know contributed to the above articles, i.e. Don Price from Johns Hopkins and Michael Shelanksi from Columbia.

    The articles clearly illustrate three important facts. First, despite claims by pro-life groups that scientists are exaggerating the importance of stem cell research for curing Alzheimer's disease, responsible scientists have not and are not saying that embryonic stem cells will cure Alzheimer's. Second, the argument for embryonic stem cell research has never been and should not be predicated on its potential to cure one disease. Third, advocacy groups are attempting to politicize science. People who have insufficient understanding of science and who have an agenda are responsible for much of the hyperbole.

    I want to comment further on the role of embryonic stem cells and Alzheimer's, to argue that while embryonic stem cells may not themselves be curative, they are very likely to contribute to therapies that will prevent deterioration and restore function in Alzheimer's disease. Cure of Alzheimer's disease requires achievement of two goals. The first is to prevent the progressive loss of neurons in the brain and the second is replacing neurons to restore function. At the present time, we don't understand why the cells are dying and do not have an effective way of preventing the loss of neurons. After stopping the progressive neural degeneration, restoration of function requires replacement of neurons. Just putting new neurons into the brain may not be sufficient. It is necessary to get the neurons to incorporate into the neuronal network, to connect up with the existing brain. While stem cells can produce new neurons, we don't know whether and how new neurons can be incorporated into the network. From this perspective, one would think that we are quite a long ways from having a cure of Alzheimer's disease and that embryonic stem cells is not the "cure" for the condition.

    Alzheimer's disease is part of a complex landscape of neurodegenerative disorders which include Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and many others. Neurons die for many reasons. Alzheimer's disease represent one very important class of degenerative disorders where cerebral cortical neurons die prematurely. Most of the research to date have focussed on excessive production of a class of proteins called amyloid precursors. There is some controversy concerning whether these proteins are the cause or a manifestation of Alzheimer's disease. Genetic studies of Alzheimer's have revealed several genes that predispose people to the disease but some of these appear to be proteins that transport molecules.

    Embryonic stem cell research will accelerate Alzheimer's research in several ways. First, if embryonic stem cell lines can be obtained from people with Alzheimer's diseases, this will provide a very important source of human cells with disease that scientists can study. Can adult stem cells be used for this as well. Yes, scientists can study adult stem cells from people with Alzheimer's disease but adult stem cells cannot (at least currently) be made into stem cell lines that can be used to grow indefinitely in culture. They differentiate in culture. However, embryonic stem cells continue to grow and divide in culture, providing a virtually unlimited supply of cells for study and therapy. If we were able to derive embryonic stem cell lines from say 100 people with Alzheimer's disease, this would provide an invaluable source of cells to study and find out how and why the disease leads to progressive neuronal death. Second, embryonic stem cells have already been shown to produce neurons when transplanted into the brain and spinal cord. While it is true that we do not yet have proof that such new neurons are incorporated into the neural network, they still represent currently the best hope for restoring function to people with Alzheimer's disease. Adult stem cells may one day do everything that embryonic stem cells do but, at the present, embryonic stem cells are the only cells that have been shown to produce neurons when transplanted into the brain and spinal cord.

    Can we do treat diseases with adult stem cells? Yes, but it will take longer to do this research with adult stem cells. Waiting is not an acceptable option for people with severe disabilities, particularly terminal neurodegenerative diseases such as Alzheimer's, Parkinson's disease, and ALS. Also, in people with genetic disease, autografts of stem cells to replace neurons is not the ideal source of cells because these cells would still contain the defective genes. Heterografts, i.e. cells from other sources, may be necessary or more desirable. One source of such cells may be embryonic stem cells that are matched or genetically manipulated to be immune compatable. Are there other therapeutic approaches, besides stem cells? Yes, of course. Research to investigate these other approaches should be continue to be vigorously pursued. Some scientists who are pursuing non-stem cell approaches to these diseases may be concerned by the publicity regarding embryonic stem cells and are afraid that their approaches may be accorded a lower priority. This is understandable but I want to emphasize that there is no consideration of stopping or slowing down other research in favor of embryonic stem cell research. At the present, the NIH is funding less than $16 milion of embryonic stem cell research, compared to over $1 billion for degenerative brain diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. There is simply no comparison.

    I think that it is critical that we do not allow science to be politicized in this way. People must let scientists do their job and stop politicizing the situation based on incomplete data. The increasing tendency of political and advocacy groups to recruit and use scientists to press their political agenda is reprehensible. The pro-life groups have had an alternative motivation, that of stopping abortion in the United States for a long time. They think that by defining blastocysts as human beings, they will be able to force legislation to outlaw abortion. This is unfortunate because embryonic stem cell research has nothing to do with abortions. Allowing research on stem cells derived from in vitro fertllized eggs that will be thrown away will have no effect on abortion. Likewise, people have tried to link somatic cell nuclear transfer (SCNT) to stem cell research without recognizing that embryonic stem cell research does not require cloning. Furthermore, there are now many ways to produce cloned stem cells much more efficiently than SCNT. The tying up of embryonic stem cell research to SCNT is unnecessary.

    [This message was edited by Wise Young on 06-13-04 at 08:56 AM.]

    #2
    Wise, could you please check your PTs? [img]/forum/images/smilies/smile.gif[/img]

    Thanks,

    -Steven
    ...an affluent suburb. 3:30 in the afternoon. 64 degrees and cloudy. the white house declined comment.
    ...it's worse than we thought. it turns out the people at the white house are not secret muslims, they're nerds.

    Comment


      #3
      embryonic stem cells have already been shown to produce neurons when transplanted into the brain and spinal cord. It is true that we do not yet have proof that such new neurons are incorporated into the neural network, they still represent currently the best hope for restoring function to people with Alzheimer's disease. Adult stem cells may one day do everything that embryonic stem cells do but, at the present, embryonic stem cells are the only cells that have been shown to produce neurons when transplanted into the brain and spinal cord.

      Can we do the above with adult stem cells? Yes, but it will take longer to do this research with adult stem cells. Waiting is not an acceptable option for people with severe disabilities, particularly terminal neurodegenerative diseases such as Alzheimer's, Parkinson's disease, and ALS.
      Thank you Dr. Young!
      I am reminded of what Dr. Irv Weissman, also a leading adult stem cell researcher said:
      "If you're in a position of authority to advise or erect a ban, then those lives are on you", Source

      "I do not believe that the same God who has endowed us with sense, reason, and intellect has intended us to forgo their use."
      - Galileo Galilei

      Comment


        #4
        Dr. Wise,
        That is so well written. Anyone that can read
        will understand the content.
        Hope everyone reads this.

        Inside of every older person,
        is a young person saying, "What the hell happened?"
        Life isn't about getting thru the storm but learning to dance in the rain.

        Comment


          #5
          How much brain does a person need? Apparently, someone can live a fairly normal life after a hemispherectomy, so it seems half a brain is sufficient.

          Alan

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

          Proofread carefully to see if you any words out.

          Comment


            #6
            Alan,

            The fact that somebody can function with half a brain is a testament to the remarkable plasticity of the brain. There is a 10% rule for recovery. For example, neurosurgeons have long known that many people will be complain of visual acuity loss due to slow-growing optic nerve glioma until it has destroyed close to 90% of the optic axons. Likewise, most people with Parkinson's disease do not get symptomatic until 90% of their substantia nigra has been destroyed. Nature has endowed our brains and spinal cord with remarkable plasticity and redundancy to handle injuries. The brain has remarkable capabilities of repairing and regenerating itself over time. The fact that we do not need our whole brain to function, that our brains have redundant neurons, has been obvious for some time. Neurologists have long known that almost everybody who has a stroke for the first time will recover almost completely and that it is the second or third stroke that is incapacitating. I also believe that there must be spontaneous neuronal replacement and regeneration in injured brains and spinal cord. The redundancy and plasticity of the brain and spinal cord is one of the reasons why I am so hopeful that a cure for brain and spinal cord injury will happen.

            I have been corresponding with a man whose wife has been in coma since January from an episode of cardiac arrest. What can I say to this man who has been told by his wife's doctors that she has zero percent chance of recovery? He had written to me saying that all he wants is to have his wife back again. Where can he go to get the therapies needed to restore his wife's brain so that their six-year old daughter (who had dialed the 911 that brought the ambulance to their home in 3.5 minutes) would have a mother again? Ten years ago, I would have said to the man that nothing can be done and the only thing that we can do is to pray and wait. Today, I don't know what to say. Should I say that stem cells may help but some people have made it so that these therapies cannot be used?

            Where is the compassion of the people of America? How is it possible that we are spending ten times more money on military occupation of Iraq this year than on research that can potentially restore this woman and thousands of others like her? The number of people who have died because we have failed to do the research far outnumber those who have died as a result of terrorism. Why have we stopped embryonic stem cell research? If there is any possibility that stem cell therapies will help, don't we have a moral obligation to try to make it so? Why are we throwing away thousands of fertilized eggs instead of using them to save lives? Why are we tying up life-saving research for political reasons? The pro-life people know that embryonic stem cell research has nothing to do with abortions, that it does not kill babies, and that such research will be beneficial to millions of people. Finally, at the same time that they have stopped embryonic stem cell research, they have not raised their voices to ensure that umbilical cord blood and adult stem cell research goes forward faster. I have tried very hard to understand but cannot.

            Wise.

            [This message was edited by Wise Young on 06-13-04 at 08:58 AM.]

            Comment


              #7
              Maryln Albert from Johns Hopkins University says "Stem-Cell Studies Should Still Begin Now" in answer to the headline "Other Approaches May Trump Stem Cells In Alzheimer's Research".
              http://www.click2houston.com/health/3408102/detail.html

              Comment


                #8
                Dr Young these are same people who will kill the doctor so he/she will stop killing babies. But will fight for somebody who is on death row for killing somebody never made sense to me either.
                "When I do good, I feel good. When I do bad, I feel bad. That's my religion." — Abraham Lincoln

                Comment


                  #9
                  foster,

                  I have many friends who oppose human embryonic stem cell research and who also strongly oppose capital punishment and radicals in the pro-life movement. I respect them and their views.

                  I have more difficulty, however, with people who claim that human embryonic stem cell research encourage abortions, that it is tantamount to killing babies, and that it will lead to baby factories. These claims are false. In fact, due to their opposition to any legislation that ban cloning, unless it also bans therapeutic cloning, opponents to embryonic stem cell research, they are encouraging unregulated use of human embryos. For the past three years, Congress has been unable to pass legislation that bans reproductive cloning or any regulation of human embryo use. This has probably resulted in more use of human embryos.

                  Wise.

                  Comment


                    #10
                    Dr. Young,

                    You can tell him about stem cells and obstructionists, but you can't give him false hope. Assume all obstructions to embryonic stem cell research disappeared tomorrow, and funding flowed like Niagra Falls - what would be your most optimistic timetable for when treatments derived from ESC would be available to humans? A decade?

                    Alan

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

                    Proofread carefully to see if you any words out.

                    Comment


                      #11
                      Alan,

                      If President Bush had not clamped down on embryonic stem cell research, I think that we would have had our first clinical trial by now. Of course, the first patients that will receive therapy would probably be those with the most desperate conditions. For example, people with ALS who have a 10% chance of 5-year survival will be among the first. Likewise, people who are dying of Alzheimer's disease would be candidates. They have little to lose and, if they die, the tissues can be examined. In my opinion, such clinical trials would be ethical and the risk benefit ratios would not be any more different than, for example, the porcine fetal neuronal transplants. I think that there is also a good chance that embryonic stem cell transplants would have been tried in spinal cord injury within a year or two from now, if President Bush had not been elected. Let me explain why:

                      1. Availability of human embryonic stem cells. The original proposal by the Clinton Administration to allow NIH to fund human embryonic stem cell research was to have private groups derive the stem cell lines. If NIH is funding the research, there will be a demand for the cells. The cells would have been made available. Doug Melton, for example, made 17 lines in his laboratory with limited resources. A Chicago clinic has made over 50 human embryonic stem cell lines. So, it is not unreasonable to assume that hundreds or perhaps even thousands of human embryonic stem cell lines would have been available in four years.

                      2. Demonstration of safety. As I pointed out above, the first patients to receive the cells will likely be terminal patients with ALS and Alzheimer's who have little to lose. If these patients die, we will know whether or not they have a propensity to develop tumors. By the way, even in 2000 when John McDonald did his study with mouse embryonic stem cells, the method of treating the cells with retinoic acid to prevent tumor formation was already known and practiced. There is no reason why this could not be done in the human trials as well. The possibility of tumor formation is the one undefined risk of transplanting these cells. The rest of the risks are well understood and reasonable.

                      3. Immune rejection. The University of Florida at Gainesville study that transplanted fetal spinal cords into people with chronic spinal cord injury did not do any tissue HLA antigen matching at all. In fact, they transplanted as many as 7 fetal spinal cords into a syrinx and MRI scans indicate that the cells survived over a year after transplantation in a majority of the patients. The patients received a short-term course of immune suppression. None of the patients had any serious side-effects from the transplantation or immunosuppression. Furthermore, Dr. Huang transplanted unmatched fetal OEG cells into the spinal cords of several hundred patients, with apparently no significant morbidity or mortality. Therefore, we can conclude that if immune rejection occured, it is not dangerous or deleterious. Even if it occurred, the transplant might still have some lasting beneficial effects. Short-term immune suppression may be sufficient to prevent rejection.

                      4. Efficacy. Please note that embryonic stem cell transplants may not effective on their own and may need to be genetically modified or combined with other therapies to have maximal effect.

                      In short, I think that we probably could be in the same position that we are right now for OEG transplants. Unfortunately, we have lost four years. In the meantime, of course, adult stem cells are rapidly catching up. If they do, that is great.

                      Wise.

                      Comment


                        #12
                        Wise

                        That's terrible - people who don't understand medicine shouldn't have so much power to stop research on treatments which are needed by people now - I know the President of the United States is supposed to have power over everything but a little knowledge is a dangerous thing - his medical advisers must have had their own agenda and he believes them

                        Comment


                          #13
                          Originally posted by Wise Young:

                          Likewise, people have tried to link somatic cell nuclear transfer (SCNT) to stem cell research without recognizing that embryonic stem cell research does not require cloning. Furthermore, there are now many ways to produce cloned stem cells much more efficiently than SCNT. The tying up of embryonic stem cell research to SCNT is unnecessary.
                          Dr. Young, would you please expand on your last point? I think it would be very helpful for many.

                          Thanks,

                          -Steven
                          ...an affluent suburb. 3:30 in the afternoon. 64 degrees and cloudy. the white house declined comment.
                          ...it's worse than we thought. it turns out the people at the white house are not secret muslims, they're nerds.

                          Comment


                            #14
                            Steven,

                            SCNT is only one of several methods of cloning. For example, most cloning today is not done with SCNT but rather fusion of cells. Parthenogenesis, for example, does not involve SCNT. Furthermore, SCNT is used for other purposes besides cloning. For example, SCNT may be used to create an egg for a infertile woman, so that her husband can fertilize the egg. So, SCNT is not necessarily cloning and SCNT is not the only way to get cloned stem cells.

                            I also want to point out the fallacy of the widespread concept that we have to have cloned stem cells for transplantation of cells. In fact, the vast majority of cell transplantations that have been carried out to date in people and animals, have been with heterograpft cells. For example, the hundreds of fetal cell transplants to people with Parkinson's disease have been with non-matched cells from aborted fetuses. Likewise, all the transplants that were done at the University of Florida at Gainesville fetal spinal cord transplants were done with non-matched tissues from aborted fetuses. Yes, in both of these trials, it appears that the tissue will engraft. It is true that the University of Florida at Gainesville trial did use a short period of immunosuppression.

                            Cloning stem cells and autografts of human adult stem cells of course would be nice because such cells would be less likely to be rejected. However, people shouldn't be jumping to the conclusion that heterografts are useless and even that non-matched heterografts are useless.

                            Wise.

                            Comment


                              #15
                              Thanks for the informative reply. Would therapies including heterografts require more development time than those using autografts [for fear of immune rejection or whatever else]?

                              -Steven
                              ...an affluent suburb. 3:30 in the afternoon. 64 degrees and cloudy. the white house declined comment.
                              ...it's worse than we thought. it turns out the people at the white house are not secret muslims, they're nerds.

                              Comment

                              Working...
                              X