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Thread: Stem Cell Therapy In Muscular Dystrophy

  1. #11
    Quote Originally Posted by hb179
    I am Hemant, from India, suffering from Muscular dystrophy (LGMD-2B) and I really enjoy being on this forum and keep myself updated by reading various discussions especially the stem cell related articles…

    I have these 2 articles and would like to sort your opinion on the following doubts…

    Therapy of Duchenne muscular dystrophy with umbilical cord blood stem cell transplantation
    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlu s&list_uids=16086277&query_hl=3&itool=pubmed_DocSu m

    Allogeneic umbilical cord blood stem cell transplantation in Duchenne muscular dystrophy
    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlu s&list_uids=15949330&query_hl=8&itool=pubmed_docsu m

    If supposing these are considered for clinical trials to treat MD then
    (1) What are the chances of improvement as per your view point ??
    (2) What are the risk ?? How can it be minimized ??
    (3) Considering both theoretical and practical aspect of the article do you find any thing that create skepticism or doubt in your knowledge… and would it “work” as suggested in the article

    Please guide me…. I know that these articles are from china and more over the case discuss are “isolated” one but this is one part of truth but other than that can these be taken seriously for further study using clinical trials… and your whole view on them. I am asking your goodself because one of my doctors got interested and wants to collect few experts’ opinions on this before taking a step forward.

    Sir, I am doing all that is possible to help and gather information from my side. I have seen many of your post being explained with simplicity to understand for all those who read them…I hope you shall put your honest opinion to guide me. .

    With regards
    hb179
    hemant_ngp@sancharnet.in
    Hemant, yes, these studies from China are quite exciting but I should point out caveats and cautions before undergoint these therapies. First, as described by Zhang, et al., (2005), the procedure requires chemotherapy (busulfan, cyclophosphamide, rabbit anti-thymocyte antibody) to destroy the bone marrow of the recipient (so that the umbilical cord blood cells will engraft). The patients received immunosuppression therapy (cycloposporin, methylprednisolone, and MMP) after the cord blood transfusion to prevent graft-versus-host reactions (which is less serious with umbilical cord blood transplants but still a real problem if and when it occurs). These are not trivial procedures. Until the cord blood cells engraft, the patient is vulnerable to infectious diseases.

    They also treated an 11-year old boy. A single unit of umbilical cord blood may not provide sufficient cells to ensure rapid engraftment for an adult. In some centers, when they use cord blood transfusions for adults, they give more than one unit.

    Finally, the cord blood cells need to be carefully matched for HLA. These are the antigens that lead to immune-rejection of transplanted cells. Xiao, et al. (2004) had earlier reported the feasibility of obtaining 6/6 HLA matches and found such units for 25% of patients. Note that HLA matching depends on the race of the individual and that the best matches are found between people of the same races.

    Wise.

    • 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

  2. #12

    Dr. Wise, Is it "worth" to take a risk to get the improvement as suggested in article

    (1) Is it "worth" to take a risk to get the improvement as suggested in these articles??

    I assume the risk are generally low and quite lot to be cautious for infection... while otherwise most of the hospitals are well equipped to handle bone marrow transplant and the chemotherapy... so looking at the overall situation, if a HLA match of 5 or 6 is obtained, which is very much feasible as per your earlier link then
    (2) how much improvement can be expected with a PROPER dose for an adult in 25-35 age group??.. Can it make me independent enough to handle myself !!!.. I am presently ambulatory with some assistance to hold to walk on even surface... (I know with such limited details it is not possible to judge and estimate the exact improvements) but can such improvements be expected in the outcome to the extent mentioned or for a complete cure over a period of time...

    (3) What would be a proper dose ?? (2 units as mentioned) to get that kind of improvement and would it be delivered iv in a single shot ??.. I hope you would excuse me for anything stupid as I am not from medical background.

    Please suggest... and thank you for your attention and time.
    hb179

  3. #13
    Quote Originally Posted by hb179
    (1) Is it "worth" to take a risk to get the improvement as suggested in these articles??

    I assume the risk are generally low and quite lot to be cautious for infection... while otherwise most of the hospitals are well equipped to handle bone marrow transplant and the chemotherapy... so looking at the overall situation, if a HLA match of 5 or 6 is obtained, which is very much feasible as per your earlier link then
    (2) how much improvement can be expected with a PROPER dose for an adult in 25-35 age group??.. Can it make me independent enough to handle myself !!!.. I am presently ambulatory with some assistance to hold to walk on even surface... (I know with such limited details it is not possible to judge and estimate the exact improvements) but can such improvements be expected in the outcome to the extent mentioned or for a complete cure over a period of time...

    (3) What would be a proper dose ?? (2 units as mentioned) to get that kind of improvement and would it be delivered iv in a single shot ??.. I hope you would excuse me for anything stupid as I am not from medical background.

    Please suggest... and thank you for your attention and time.
    hb179
    Nobody has the answer to the questions that you ask. The possibility of this working for adults is unknown, because it has not been tried (to my knowledge).

    The risks are quite significant and that is why the bone marrow replacement therapy has not been used so very much, even though it could potentially cure many autoimmune diseases (such as multiple sclerosis, diabetes, lupus erythematosus) and genetic hematopoietic diseases (such as sickle cell anemia, thalassemia, immune deficiency, idiopathic thrombocytopenic purpura). These risks include:
    • The units may not engraft. This means that they will have to try other units, bone marrow, or other sources of cells. During the period of trying units, you are bereft of your own immune system and therefore may die of infection. Even if the unit engraft, you need to be in a special infection-free unit of the hospital during the period after chemotherapy that destroys your own bone marrow and when the engraftment occurs. That is one fo the main reasons why this procedure is so expensive (typically US$100,000 or more).
    • The transplanted cells may regard your body as "foreign" and attack it. This is called graft-versus-host disease (GVHD) and mild GVHD occurs in as many as 20-40% of people who get heterologous stem cell transplants of hematopoietic cells. About 10% of the people may get severe GVHD which must be treated with long-term immunosuppressive drugs such as cyclosporin and methylprednisolone. In fact, as the paper from Zhang, et al. cited below suggests that they use prophylactic immunosuppression in the patients that receive umbilical cord blood transplants. The closer the HLA matching and if the blood comes from a relative, the risk of GVHD decreases.
    • The chemotherapy (like all chemotherapies) and the immunosuppression increases the risk of cancer in your body. The reason is of course because your immune system is eliminates stray cancer cells. You may get a variety of tumors, particularly of the hematopoietic system, including leukemia, lymphoma, and other cancers after having had the procedure. Unfortunately, because most umbilical cord blood and bone marrow transplants are being done for patients who have cancer, it is difficult to judge the actual risk imposed by the procedure.

    An unanswered question is how and why umbilical cord blood transplants help Duchenne muscular dystrophy. As you know, Duchenne's muscular dystrophy is a disease where a protein called dystrophin is absent or malfunctional. This protein helps maintain motoneurons. The initial symptoms are wasting ofo the muscles in the hips, pelvis, thighs, and shoulders but generally extend to include all muscles of the body. Duchenne's is an X-linked recessive genetic disease that most affects boys (because boys have only one X-gene and the absence or malfunction of this gene from the mother results in the disease, whereas girls of two X-genes and the girl would need to get the diseased gene from both the mother and father in order to manifest the symptoms). It is not clear how and why replacing hematopoietic cells in the body of the children results in support of motoneurons in the central nervous system. But, the clinical trial suggests that it does.

    Wise.

  4. #14

    Thank you Dr. Wise.

    Your goodself explained it very nicely and to my satisfaction… the risk and cautions are explained in complete details and I got the whole picture.

    Dr. Wise, For any Allogeneic umbilical cord stem cell transplant the procedure and the risk associated are inevitable and the delivery of such stem cell having potential would always remain a problem…

    Would you agree that because of infection risk and cost factor these heterologous stem cell transplants HAVING HUGE POTENTIAL to treat many such diseases are not utilized but are very much feasible?? … comment pls.

    Anyway, your opinion and suggestions were very important and to my entire satisfaction… and I try to understand them to the best of my ability.

    Regards
    hb179

  5. #15
    hb179,

    Significant advances in umbilical cord blood and bone marrow transplants have been made in the last several years. They use to use whole body radiation to damage the bone marrow so that engraftment from the new cells would occur. Radiation turned out to be more damaging to the body and less effective than chemotherapy. Clinicians have been using smaller doses and shorter course of chemotherapy and finding that this works as well. However, it is very difficult field to experiment because failure of engraftment is deadly. So, clinicians are reluctant to push the limits of the procedures. It only takes a death of one child to make a clinician gunshy.

    Over the past two years, scientists are discovering that adult stem cells do not engraft if there are no "niches" for the cells to settle into and do their work. Little changes in procedure may very well have substantial effects. For example, why infuse the umbilical cord blood or bone marrow (a lot of the cells are wasted). Why not put them directly into the places where there are niches? If we knew the cells that need to be replaced, perhaps it will be possible to use antibodies to attack these cells selectively and open up the niches? So, in my opinion, the procedures will get safer, faster, and better in the coming years.

    As I pointed out below, it is not clear why umbilical cord blood cell infusions protect motoneurons that are missing or have a dysfunctional dystrophin. Are the umbilical cord blood cells getting into the nervous system and providing the dystrophin? Are they making new motoneurons and replacing dysfunction motoneurons? Having answers to these questions would greatly help improve the procedures so that we can maximize the treatment effects. For example, if indeed getting the umbilical cord blood cells into the spinal cord or brain is the goal, we should be giving the cells intrathecally or intraspinally, instead of just infusing the cells and diluting them all over the body.

    Wise.

  6. #16

    Smile Dr. Wise, A request, if easily possible.

    Dr. Wise, Can you get me the e-mail to contact with any of these articles, if easily available...
    1) Therapy of Duchenne muscular dystrophy with umbilical cord blood stem cell transplantation
    2) Allogeneic umbilical cord blood stem cell transplantation in Duchenne muscular dystrophy.
    3) A probability analysis for HLA matching in adult stem cell transplantation treating nervous genetic diseases.


    so as to seek there personal opinion as they might have through experience... . (the email address in your last suggestion is not working).. thank you for everything, i love these board.

    with regards
    Hemant

  7. #17
    Hemant, may I suggest that you simply look it up on internet. That is what I do. Wise.

  8. #18

    Md

    Dear Dr. Rajeev,
    My Uncle is also suffering from Mascular Dystropyhy. I will put all the details of his disease after talking with him. How is your progress with stem cell treatment? We are also planning to go for it. Your suggestion and comments will help us a lot.
    Regards,
    Mushabbir

  9. #19

    Information Rgdg Stem Cell Therapy for LGMD

    Dear Dr Young,
    I am Vineet Aggarwal from India, my brother Vikas is suffering from Limb Girdle Muscular Dystrophy (LGMD).
    Though he can still walk around freely but has problem climbing stairs, as he needs support. His problem from last 2 years has been restricted to his lower limbs.
    I wanted to enqurie about an organization that I recently came through on internet. The organization is a UK based organization called Regenecell and boasts of treatments in Mumbai, India by Dr Hansnin Patel. Here is the link to their site -

    www.regenecell.com

    Their site even has a logo of Good Laboratory Practice (GLP) approved by US FDA, but does not have any other logos of Good Clinical Practices (GCP) etc.
    Per the site they offer umblical cord stem cell therapy for LGMD with a mix of Mesochymal cell (excuse me If I got the wrong spelling).
    Can I request you to please suggest, if this would be a viable option for us to follow.

    Best Regards,
    Vineet Aggarwal
    vineet_aggarwal@hotmail.com

  10. #20

    Can Allogenic Mesenchymal stem cell benefit MD??

    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.

    Sir, I would like to know if there are any cracks in the closed tunnel to see some light for people like us and be hopeful??... :-) ...... Any evidence to support the above pre-position or any mouse model study to rely on... Your take would be as equal.

    Your guidance has always satisfied my haunting doubts and your expertised knowledge on stem cell shall always be required to take a step forward for our betterment.

    With regards
    Hemant
    P.S. The article of vineet aggarwal and www.regenecell.com is encouraging.

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