Page 3 of 13 FirstFirst 123456789101112 ... LastLast
Results 21 to 30 of 130

Thread: Stem Cell Therapy In Muscular Dystrophy

  1. #21
    The term allogenic means from a different individual in the same species. So, an allogenic mesenchymal stem cell graft for you would mean a stem cell graft from another human. There is indeed much speculation that mesenchymal stem cells are immune-privileged. However, recent studies suggest that they are escaping immune rejection because they are anti-immune rather than immune-privileged. Anti-immune means that they are probably turning off immune cells. What is now known is the extent to which the progeny (the offspring) of the mesenchymal are also immune-privileged or anti-immune, once they differentiate into neurons or muscles. Note that allogenic mesenchymal stem cels are necessary because most muscular dystrophies are genetic disorders. Therefore, if mesenchymal stem cells are obtained from yourself (autografts), they will not solve the problem.

    The most common form of childhood onset muscular dystrophy is Duchenne's and it is associated with a the absence of dystrophin, a protein that is essential for maintaining muscles. For several years now, doctors have suggested that mesenchymal stem cells are useful for muscular dystrophy, particularly a type of cells called mesoangioblasts (Source). The treatment has been reported to be beneficial in mice (Source) or dogs (Source) that don't have dystrophin. However, there has been disappointingly few clinical trials that have shown any benefit of mesenchymal stem cell grafts in humans. However, several studies in Guangzhou have reported beneficial effects of HLA-matched umbilical cord blood infusions in patients with muscular dystrophy. I have discussed these before here.
    Zhang C, Chen W, Xiao LL, Tan EX, Luo SK, Zheng D, Ye X, Li Z, Lu XL and Liu Y (2005). [Allogeneic umbilical cord blood stem cell transplantation in Duchenne muscular dystrophy]. Zhonghua Yi Xue Za Zhi 85: 522-5. OBJECTIVE: To study the feasibility of treatment of Duchenne muscular dystrophy (DMD) with umbilical cord stem cell transplantation. METHODS: HLA matching was conducted for a 11-year-old DMD boy with family history was underwent umbilical cord blood stem cell transplantation and a sample of umbilical cord stem cells with 5 matched HLA sites was found in the cord blood bank with 27.32 x 10(8) nucleated cells, about 2.6 times that of the treatment dosage for him. After pretreatment with busulfan 14 mg/kg.d, cyclophosphamide 50 mg/kg.d, and rabbit anti-human thymocyte globulin 10 mg/kg.d, the allogeneic cord blood stem cells were transplanted intravenously. Cyclosporin A, methylprednisolone and MMF were used after the transplantation so as to prevent graft versus host reaction. Prostaglandin E1 was used to prevent Budd-Chiari syndrome, and ganciclovir was used to prevent cytomegalovirus infection. At the same time, Gran, granulocytic cell stimulating factor, and gammaglobulin were also used. Biochemistry test, including serum creatine kinase (CK), was conducted. Evidence of reconstruction of blood making, including conversion of blood type, was observed. PCR-STR analysis was used to observe the status of implantation of the donor umbilical cord blood stem cells. RESULTS: (1) 12 days after transplantation, the white blood cells (WBC) of peripheral blood were 0.5 x 10(9)/L, 14 days after, the numbers of WBC and neutrophils were 1.0 x 10(9)/L and 0.6 x 10(9)/L respectively. In 37 days, granulocytic cell stimulating factor was no more used, the peripheral blood WBC fluctuated around 3.34 approximately 12.2 x 10(9)/L. In the 27th day, the number of blood platelets was more than 20 x 10(9)/L and hemoglobin rose to 88 g/L. On the 24th day red blood cells transfusion was stopped. (2) In the 42nd day, the blood type of the patient transformed from type A before transplantation to type AB (the blood type of transplanted stem cells is type B). (3) PCR-STR test of the peripheral blood made 17, 26, and 42 days after transplantation showed that the gene type of the patient was mixed mosaic: The ratio of donor gradually increased from 40% approximately 45% to 55% approximately 65%. (4) In the 38th day I degrees GVHD appeared. (5) serum CK level declined from 6000 U/L to 600 approximately 2200 U/L. (6) In the 42nd day, physical examination revealed obviously improvement in walking, turning the body over, and standing up. CONCLUSION: This is first case of prospective clinical transplantation on DMD by allogeneic cord blood stem cell. Umbilical cord stem cell transplantation helps re-build blood-making function, and improve locomotive function with a mild GVHD reaction. The genotype of rebuilt blood is mosaic but the ratio of gene mosaic gradually turn from recipient gene type > donor gene type to recipient gene type < donor gene type. The serum CK level decreases significantly after transplantation, which may slow down the necrosis of muscle cell. DMD patient will be benefited by stem cell transplantation. Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15949330

    Xiao LL, Chen W, Zhang C, Liu ZL, Ye X, Zhang WD and Yi Y (2004). [A probability analysis for HLA matching in adult stem cell transplantation treating nervous genetic diseases]. Zhongguo Shi Yan Xue Ye Xue Za Zhi 12: 845-8. The aim of this study was to investigate the clinical feasibility of adult stem cell transplantation for lethal mono-gene inherited disease, Duchenne muscular dystrophy (DMD). A total of 30 blood samples from DMD patients were genotyped with HLA-A,-B and -DR alleles by means of polymerase chain reaction-reverse sequence specific oligonucleotide (PCR-RSSO). The HLA gene types in 30 DMD patients were compared with those of 668 unrelated donors from Umbilical Cord Blood Center of Guangdong Province and 34 910 unrelated donors from Chinese Bone Marrow Bank. The results showed that HLA gene of the DMD group was inherited in normal distribution. There was no striking difference of HLA-A, -B and -DR alleles expression between the DMD patients group and control healthy group. 25% of the DMD patients got suitable donors for stem cell transplantation, in which 15 patients found donors with >or= 5/6 HLA match at the Umbilical Cord Blood Center of Guangdong Province, i.e. occupying 50% of the total. Eight patients got 6/6 HLA matching donors at the Chinese Bone Marrow Bank, i.e. occupying 26% of the total. It is concluded that stem cells transplantation therapy for DMD patients is feasible, which will benefit these patients suffered from the lethal neuromuscular disease, and create a new way to treat this tough nervous system disease. Guangzhou Blood Center, Guangzhou, 510095 China. lulux-640@hotmail.com http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15631675
    [quote]


    Quote Originally Posted by hb179
    Dear Dr. Wise,

    Can Allogenic Mesenchymal stem cell benefit MD?? As it is a known fact that mesenchymal do not require HLA matching and the risk associated with M-SC is low due to avoidance of immuno-supressor, hence gaining a lot of attention these days.

  2. #22

    Does mesenchymal stem cell from any source have the same properties??

    Dear Dr. Wise,

    Sir, in India I know many hospitals who are trying and doing research with allogenic (donor) M-SC, but so far no results are visible with Adult allogenic M-SC even after 9 months. 4 doses IV were received and each dose was 1 million per kg weight to the patient. With no results yet the conclusion seems obviously going down side.

    Now, i came to know about a doctor who is going to conduct research with M-SC derived from fats with whatever instructions/signals needed to make them muscle/dystrophin and he seems to be very confident of getting desired results. He has successfully made insulin with same M-SC and treating humans at his clinic/hospital.

    I guess that all M-SC which may be derived from any source (Adult, Fat or Umbilical) will have the same inheritant properties. Or is it not. I would like to know whether they (M-SC) differ with there potential ability and properties depending on source? Or secondly, does the process of culturing the stem cell make a huge difference? your guidance can remove my confusion.
    With regards
    Hemant

  3. #23

    mesoangioblasts ??

    Does Adult M-SC derived from bone marrow contain mesoangioblasts cells ? And will they (mesoangioblasts) work when given in IV on DMD/LGMD when given as Allogenic M-SC dose?

    I know that lot more study is needed and as i have no far relation with medical field than this disease, so, I could land up very impertinent questions. I hope you shall please forgive my ignorance at times.
    With regards and high respect,
    Hemant

    [quote=Wise Young] For several years now, doctors have suggested that mesenchymal stem cells are useful for muscular dystrophy, particularly a type of cells called mesoangioblasts (Source). The treatment has been reported to be beneficial in mice (Source) or dogs (Source) that don't have dystrophin. However, there has been disappointingly few clinical trials that have shown any benefit of mesenchymal stem cell grafts in humans.

  4. #24
    Quote Originally Posted by hb179
    Does Adult M-SC derived from bone marrow contain mesoangioblasts cells ? And will they (mesoangioblasts) work when given in IV on DMD/LGMD when given as Allogenic M-SC dose?

    I know that lot more study is needed and as i have no far relation with medical field than this disease, so, I could land up very impertinent questions. I hope you shall please forgive my ignorance at times.
    With regards and high respect,
    Hemant

    Quote Originally Posted by Wise Young
    For several years now, doctors have suggested that mesenchymal stem cells are useful for muscular dystrophy, particularly a type of cells called mesoangioblasts (Source). The treatment has been reported to be beneficial in mice (Source) or dogs (Source) that don't have dystrophin. However, there has been disappointingly few clinical trials that have shown any benefit of mesenchymal stem cell grafts in humans.
    Allogenic (from another individual) cells must be HLA-matched or else they are likely to be rejected. It seems that the bone marrow has mesenchymal stem cells that are pluripotent and can supply stem cells to the rest of the body. Unfortunately, nobody has markers that can identify these cells, they are quite rare even in the bone marrow, and obtaining sufficient quantities of these cells and transplanting them so that they engraft is an unsolved problem.

    The best cells for transplant are of course autografts. However, because muscular dystrophy is a genetic disease, it makes no sense to transplant cells with the same genes. There are of course HLA-matching for bone marrow cells but even with large registries of 4-5 million people, matches often cannot be found. Even if good matches are found, it is best to have matched cells from a close relative to get the best chance of engraftment.

    Umbilical cord blood cells, for reasons that are still not well understood, apparently will engraft even with 4/6 HLA match whereas bone marrow requires 6/6. So, a group in China has been using umbilical cord blood cells to treat muscular dystrophy in kids. It makes sense to get the cells to be accepted by the bone marrow and then it will shower the body with stem cells for the rest of one's life, replacing presumably muscle cells and other cells.

    Finally, there is the consideration of opening up niches in the bone marrow to accept grafts. Normally, stem cells survive and engraft only if they get into a tissue that has a "niche" for them. To open up these niches to bone marrow and umbilical cord grafts, many clinicians use whole body radiation or chemotherapy to destroy existing stem cells, opening up their niches.

    Whole body radiation is too problematical and has a high risk of causing cancer and so that is not being used today. However, chemotherapy is being used and there is evidence that relatively that relatively mild chemotherapy will work. This is now being used for umbilical cord blood cell transplants to treat thalassemia, for example, in kids.

    Finally, bone marrow and umbilical cord blood both pose a risk of a condition called graft-versus-host-disease (GVHD). This condition occurs when the transplanted cells attack the body, thinking that it is "foreign". If and when this happens, one gets essentially an autoimmune condition. Bone marrow transplants have a very high risk of GVHD (>60%) while umbilical cord blood cells have a lower risk (<20%).

    I am not sure that there is all that much distinction between the various progenitor cells for muscle and stem cells. At the present, I have not seen any reliable method of segregating muscle progenitor cells from others and growing them in large quantities. However, the first company to do so will likely become very wealthy because it will address so many diseases, not just muscular dystrophy but muscle problems of all sorts, and perhaps even for recovery from non-use atrophy.

    Wise.

  5. #25
    Senior Member dr_bubo's Avatar
    Join Date
    May 2003
    Location
    Budapest
    Posts
    377

    check this video

    http://www.youtube.com/watch?v=kUwnMX8ht3U

    he is right wish we had more so open minded people like Mr Harris

  6. #26

    Duchene's Muscular Dystrophy

    Dr. Young - Sir, my 3 year old son has been diagnosed with Duchene's Muscular Dystrophy. He has an exon deletion at 44-47. I have been researching quite a bit and have found significant Umbilical Cord Blood Stem Cell (UCBSCs) advances with this disease. The good news is that we kept his UCBSCs. The even better news is, he has a girl twin who is normal and we kept hers as well. We also kept his 5 year old brother's cord blood stem cells. Even more interesting, though my wife has not been tested to see if she is a carrier, she is an identical twin and her sister tested negative as a carrier of this disease as they were not through having children. As a result, they believe my son's DMD is a mutation that simply took place during the pregnancy without any contribution from my wife. My wife's twin sister has 3 children currently, and they kept their cord blood stem cells as well (they are all healthy children). My question is this, do you know where I go from here? We have kept all of these stem cells that can all be utilized by my son who has DMD, but I do not know where to go now or what to do. China has made incredible advances as I also noted in your previous post. I know a patent was recently filed from MASS., USA in which they used UCBSCs in animals and the subject started producing its own dystrophin and started walking. I welcome your guidance as I am lost as to what I need to do with all of these precious cord blood stem cells. Thank you in advance for any positive information you can provide.

  7. #27
    Quote Originally Posted by ydxyrbc View Post
    Dr. Young - Sir, my 3 year old son has been diagnosed with Duchene's Muscular Dystrophy. He has an exon deletion at 44-47. I have been researching quite a bit and have found significant Umbilical Cord Blood Stem Cell (UCBSCs) advances with this disease. The good news is that we kept his UCBSCs. The even better news is, he has a girl twin who is normal and we kept hers as well. We also kept his 5 year old brother's cord blood stem cells. Even more interesting, though my wife has not been tested to see if she is a carrier, she is an identical twin and her sister tested negative as a carrier of this disease as they were not through having children. As a result, they believe my son's DMD is a mutation that simply took place during the pregnancy without any contribution from my wife. My wife's twin sister has 3 children currently, and they kept their cord blood stem cells as well (they are all healthy children). My question is this, do you know where I go from here? We have kept all of these stem cells that can all be utilized by my son who has DMD, but I do not know where to go now or what to do. China has made incredible advances as I also noted in your previous post. I know a patent was recently filed from MASS., USA in which they used UCBSCs in animals and the subject started producing its own dystrophin and started walking. I welcome your guidance as I am lost as to what I need to do with all of these precious cord blood stem cells. Thank you in advance for any positive information you can provide.
    Dear ydxyrbc,

    I believe that umbilical cord blood treatment is the treatment of choice for muscular dystrophy today. You should understand that there is a risk and you must get the transplant done by the best centers for this purpose. I have a great deal of respect for Joanne Kurtzberg at Duke and I suggest that you contact her for her advice. I don't know or think that she is currently doing cord blood therapy transplants for babies with muscular dystrophy.

    Please understand that there is a risk in the procedure because your son will probably need myeloablation to eliminate (or reduce) his existing stem cells that may contain the gene and the transplanted umbilical cord blood stem cells may cause a complication called graft-versus-host-disease. However, the risk of such transplants has fallen to 1-2% and improving every year.

    In my opinion, I think that the benefit now is worth the risk of the myeloablation and transplant. Muscular dystrophy is a progressive disease and the risk of death is significantly higher than the transplantation. You should get other doctor's opinions. The decision may be to wait for a year or two until the technology and statistics get even better but I think that the direction is a good one.

    Wise.

  8. #28
    Thank you so much for the direction and quick reply. I will be contacting her soon through some of our doctors. My son's Neurosurgeon, Dr. Jerry Oakes here in Birmingham, did his fellowship at Duke and then spent 10 years I believe at the institution. He originally discovered a Syrinx on my DMD son's spine (T3 I believe) and we originally thought that was all that we had to worry about until the DMD diagnosis. The Syrinx continues to get smaller ever year based on the MRIs and ironically enough, is not related to the DMD at all. Oh how I wish that all we had to worry about was the Syrinx. I will continue to pursue things like this and your opinion and guidance is appreciated more than you will know. I hope you and yours have a great holiday season and a prosperous New Year. I will keep you updated. Thank you sir...

  9. #29

    Stem Cell Treatment for DMD

    Dear ydxyrbc,
    My name is Sagar Kapadia and I live in India. My 19 month old nephew suffers from DMD. I found this page on the internet, in which Dr Young has asked you to contact Dr Joanne Kurtzberg at Duke. I would be highly obliged if you could provide me with the email address of Dr Joanne Kurtzberg at Duke, since we wish to seek her advice regarding stem cell treatment. There is a company in China, Beike Biotech, which offers treatment for DMD. In addition, we also found the articles by Dr Zhang C. in which he reports the treatment of an 11 year old boy and a 12 year old boy. However, the thought of chemotherapy and destroying the bone marrow makes us very nervous, and we do not know whether the risk is worth taking.

    My email address is srk1974@gmail.com

    Thanks and Regards
    Sincerely
    Sagar Kapadia

  10. #30
    Dear Sagar Kapadia-

    I am going through my son's Pediatric Neurosurgeon to contact Dr. Kurtzberg at Duke since he went to Duke and was there for 10+ years. Due to the Holiday Season, I have not spoken directly to his Neurosurgeon. I plan on contacting him next week. Once I do, I will ask that he provide me with her contact information.

    Please keep me updated with any information you may uncover and I will do the same. Once I get her contact information, I will send it your way. Together maybe we can beat this horrible disease!

    Take Care!
    ydxyrbc

Similar Threads

  1. Republican Senate Leader Frist to back ESC research!
    By Donny247 in forum Funding, Legislation, & Advocacy
    Replies: 45
    Last Post: 08-09-2005, 08:00 AM
  2. Why are embryonic stem cells important?
    By Wise Young in forum Cure
    Replies: 48
    Last Post: 05-04-2005, 02:49 AM
  3. Replies: 9
    Last Post: 11-13-2004, 08:26 AM
  4. Replies: 104
    Last Post: 07-24-2004, 12:56 PM
  5. LANCET´S ARTICLE
    By KIM in forum Cure
    Replies: 2
    Last Post: 10-04-2002, 09:52 AM

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •