- Ankylosing Spondylitis
- Cerebral Palsy
- Charcot-Marie-Tooth Disease (CMT)
- Crohn's Diseases
- Guillain-Barre’ Syndrome
- Hashimoto's Thryroiditis
- Kidney Diseases
- Myasthenia Gravis
- Macular Degeneration
- Lupus (SLE)
- Multiple Sclerosis
- Psoriatic Arthritis
- Parkinson’s disease
- Rheumatoid Arthritis
- Ulcerative Colitis
Stem Cell Therapy for CMT – Stem Cells CMT
Charcot-Marie-Tooth disease (CMT), known also as Hereditary Motor and Sensory Neuropathy (HMSN), Hereditary Sensorimotor Neuropathy (HSMN), or Peroneal Muscular Atrophy, is a heterogeneous inherited disorder of nerves (neuropathy) that is characterized by loss of muscle tissue and touch sensation, predominantly in the feet and legs but also in the hands and arms in the advanced stages of disease. Presently incurable, this disease is one of the most common inherited neurological disorders, with 37 in 100,000 affected.
Charcot-Marie-Tooth disease is caused by mutations that cause defects in neuronal proteins. Nerve signals are conducted by an axon with a myelin sheath wrapped around it. Most mutations in CMT affect the myelin sheath. Some affect the axon.
The most common cause of CMT (70-80% of the cases) is the duplication of a large region in chromosome 17p12 that includes the gene PMP22 . Some mutations affect the gene MFN2, which codes for a mitochondrial protein. Cells contain separate sets of genes in their nucleus and in their mitochondria. In nerve cells, the mitochondria travel down the long axons. In some forms of CMT, mutated MFN2 causes the mitochondria to form large clusters, or clots, which are unable to travel down the axon towards the synapses . This prevents the synapses from functioning. CMT is divided into the primary demyelinating neuropathies (CMT1, CMT3, and CMT4) and the primary axonal neuropathies (CMT2), with frequent overlap.
Another cell involved in CMT is the Schwann cell, which creates the myelin sheath, by wrapping its plasma membrane around the axon in a structure that is sometimes compared to a.
Neurons, Schwann cells, and fibroblasts work together to create a working nerve. Schwann cells and neurons exchange molecular signals that regulate survival and differentiation. These signals are disrupted in CMT. 
Demyelinating Schwann cells causes abnormal axon structure and function. They may cause axon degeneration. Or they may simply cause axons to malfunction. The myelin sheath allows nerve cells to conduct signals faster. When the myelin sheath is damaged, nerve signals are slower, and this can be measured by a common neurological test, electromyography. When the axon is damaged, on the other hand, this results in a reduced compound muscle action potential (CMAP).
A growing body of evidence suggests strongly that the use of stem cells to address the primary componants of both inflammation and demylination has a direct effect on this disease. Much of the research, that also applies, has focused on Multiple Sclerosis another demylinationg disease with a larger incidence world wide. There is a growing body of literature supporting the contention that with stem cell therapy Schwann cells and other componants of the immune system, that adversely affect CMT patients, can be influenced to reverse their typical progressive dysfunction.
Our patients have now documented significant changes in multiple areas of function. Most notable has been in their ability to walk, maintain balance and have more consistent and higher levels of energy. These changes allow for a substantial quality of life changing affair. Interestingly we have seen progressive improvements over the period of a year post treatment. Only time will determine the nature of how much change can take place. It should be understood that currently all the CMT patients are seniors. We expect that with earlier treatment even better results can be achieved.
Autologous Stem-Cell Transplant Phases :
After a review of your medical records and discussions with medical staff, a protocol is designed especially for you. Specifics of your condition are addressed along with any special needs. It may be similar to the one illustrated below:
At the clinic you will be examined by our physicians. Information including any risks and expectations concerning your treatment, plus answers to any questions you may have will be addressed. A blood draw, to determine cell counts and other chemistries will be collected and cell expansion medication may be administered. Then you will return to your hotel for a restful day or a good nights sleep.
At the clinic our physician/s will review the laboratory results, determine if the cell count is within range, and discuss the response to the stimulation. They may or may not provide additional cell expansion medications and may add adjunctive treatments. The levels of your response will determine if you would return to the hotel, with little restriction on your activities, or possibly go forward with harvesting and processing your cells.
If the cell count and viability is appropriate for harvest either a bone marrow or adipose collection will be utilized. We typically use local anesthetics for adults and general anesthesia for youngsters. The entire procedure normally takes less than 30 minutes. Although some pain is felt when the needle is inserted, most patients do not find the bone marrow or adipose collection procedure particularly painful.
We recently placed a number of videos on our website interviewing our patient’s who discuss the procedure and their lack of discomfort.
After the collection you may return to the hotel, with some restrictions. The bone marrow or adipose collected is processed in our contract State-Of-Art laboratory by trained staff, under the supervision of the lab physician.
As an alternative to the above, cord blood may be used based on the patient’s individual medical condition and options.
At the clinic or at the hospital you will be treated by IV infusion and/or a lumbar puncture, which injects the stem cells into the cerebrospinal fluid. This route transports the cells into the spinal canal and the brain directly influencing the nervous systems, thereby eliminating the brain/blood barrier. If a lumbar puncture is performed, the patient will be required to restrict their activities and potentially spend the day in the hospital or at their hotel.
At the clinic or hospital the patient will receive a post-treatment examination and evaluation prior to their release. Additional therapy and treatments may also be utilized to maximize the placement and activities of the procedure.
Day 6: Optionally there may be the use of additional ancillary therapies to enhance the procedure.
What makes our treatment different ?
Our approach includes stimulation, prior to collection, processing and expansion of the cell along with the use of growth factors, together with an integrated medical approach. This maximizes the growth and implantation potentials yielding optimized potentials of making changes in your disease.
Our staff physicians are all board certified, in their field with years of experience. Your team includes both primary and ancillary care professionals devoted to maximizing your benefits from the procedures. We enroll you in an open registry to track your changes independently, for up to 20 years.
As our patient we also keep you abreast of the newest developments in stem cell research. This is an ongoing relationship to maintain and enhance your health.
Our promise is to provide you with travel and lodging support, access to bilingual staff members throughout the entire process and most importantly the best medical care possible.
References and Articles:
Immune effects of mesenchymal stem cells: implications for Charcot-Marie-Tooth disease.
June 4, 2008
Riordan NH,Leal A, Ichim TE, Marleau AM, Lara F, Kaushal S, Riordan NH.
School of Biology and Neuroscience Research Program, University of Costa Rica, San José, Costa Rica, USA.
CMT1 is characterized by demyelination and aberrant immune activation making this condition an ideal target for exploration of MSC therapy, given the ability of these cells to promote sheath regeneration as well as suppress inflammation.
Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates
Nature Medicine 9, 1520 – 1527 (2003) Published online: 16 November 2003; | doi:10.1038/nm963 Fernando D Camargo1, 2, Rahshaana Green1, Yassemi Capetenaki3, Kathyjo A Jackson1, 4 & Margaret A Goodell1, 2, 4]]
Our results indicate that circulating myeloid cells, in response to inflammatory cues, migrate to regenerating skeletal muscle and stochastically incorporate into mature myofibers. (authors note: This may be one of the most suggestive papers detailing a method of forestalling further declines and injuries in this patient population, by regeneration of muscle mass)
Muscle-Targeted Gene Therapy of Charcot Marie-Tooth Disease is Dependent on Muscle Activity Stephan Klossner1, Marie-Noëlle Giraud2, Sara Sancho Oliver3,David Vaughan4 and Martin Flück
InTech, August 2011
Our observations indicate that muscle dysfunction with Charcot-Marie-Tooth (CMT) is not due to a single, central mechanism. A novel, contraction-dependent feedback mechanism is identified that controls myelin-specific transcripts via a muscle fibre-related pathway. Somatic transfection of muscle fibres with the mechanosensor FAK prove the concept that pmp22 expression which is lowered in CMT can be stimulated when combined with skeletal muscle use. This indicates that muscle activity is a confounding variable that warrants exploration.
The findings are consistent with documenting the fact that a whole person approach, not an isolated gene manipulation is critical to effectuating change in CMT disorders.
. Krajewski KM, Lewis RA, Fuerst DR, et al. (2000). “Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A”
Brain 123 ( Pt 7): 151627. doi
2. Baloh RH, Schmidt RE, Pestronk A, Milbrandt J (2007). “Altered axonal mitochondrial transport in the pathogenesis of Charcot-Marie-Tooth disease
from mitofusin 2 mutations”
J. Neurosci. 27 (2): 42230. doi :10.1523/JNEUROSCI.4798-06.2007
3. Berger P, Young P, Suter U (2002). “Molecular cell biology of Charcot-Marie-Tooth disease”
Neurogenetics 4 (1): 115. doi 4.
Immunosuppressive properties of mesenchymal stem cells: advances and applications.
Mesenchymal stem cells (MSCs) have been isolated from a variety of tissues, such as bone marrow, skeletal muscle, dental pulp, bone, umbilical cord and adipose tissue. MSCs are used in regenerative medicine mainly based on their capacity to differentiate into specific cell types and also as bioreactors of soluble factors that will promote tissue regeneration from the damaged tissue cellular progenitors. In addition to these regenerative properties, MSCs hold an immunoregulatory capacity, and elicit immunosuppressive effects in a number of situations. Not only are they immunoprivileged cells, due to the low expression of class II Major Histocompatibilty Complex (MHC-II) and costimulatory molecules in their cell surface, but they also interfere with different pathways of the immune response by means of direct cell-to-cell interactions and soluble factor secretion. In vitro, MSCs inhibit cell proliferation of T cells, B-cells, natural killer cells (NK) and dendritic cells (DC), producing what is known as division arrest anergy. Moreover, MSCs can stop a variety of immune cell functions: cytokine secretion and cytotoxicity of T and NK cells; B cell maturation and antibody secretion; DC maturation and activation; as well as antigen presentation. It is thought that MSCs need to be activated to exert their immunomodulation skills. In this scenario, an inflammatory environment seems to be necessary to promote their effect and some inflammation-related molecules such as tumor necrosis factor-α and interferon-γ might be implicated. It has been observed that MSCs recruit T-regulatory lymphocytes (Tregs) to both lymphoid organs and graft. There is great controversy concerning the mechanisms and molecules involved in the immunosuppressive effect of MSCs. Prostaglandin E2, transforming growth factor-β, interleukins- 6 and 10, human leukocyte antigen-G5, matrix metalloproteinases, indoleamine-2,3-dioxygenase and nitric oxide are all candidates under investigation. In vivo studies have shown many discrepancies regarding the immunomodulatory properties of MSCs. These studies have been designed to test the efficacy of MSC therapy in two different immune settings: the prevention or treatment of allograft rejection episodes, and the ability to suppress abnormal immune response in autoimmune and inflammatory diseases. Preclinical studies have been conducted in rodents, rabbits and baboon monkeys among others for bone marrow, skin, heart, and corneal transplantation, graft versus host disease, hepatic and renal failure, lung injury, multiple sclerosis, rheumatoid arthritis, diabetes and lupus diseases. Preliminary results from some of these studies have led to human clinical trials that are currently being carried out. These include treatment of autoimmune diseases such as Crohn’s disease, ulcerative colitis, multiple sclerosis and type 1 diabetes mellitus; prevention of allograft rejection and enhancement of the survival of bone marrow and kidney grafts; and treatment of resistant graft versus host disease. We will try to shed light on all these studies, and analyze why the results are so contradictory.
Comment: This is an excellent example of a literature review and then subsequent inquiry into some of the known and as yet to be found pathways that allow the stem cells their ability to positively impact diseases. I think it’s interesting that “mother nature’ allows these cells such a pervasive impact on the inflammatory processes. Great design…
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Andrew is thriving. We have seen and continue to see major improvements. He has matured beyond anything I can explain (I have had to rapidly adjust my parenting as I now have a much older & more sophisticated child), his comprehension (perhaps better to say his ability to express and act upon his comprehension) is now age appropriate.Read more
Hello, When we came from Cancun the first week we noticed an improvement in eye contact. It improved about 70%. His attention improved about 50% and he was more in our world when it comes to understand what it happening around him. He lost some of his attention for the last two weeks but it is still better than it was prior stem cells and even Janik BIs therapist say it is easier to work with Janik in ABA because his eye contact is better and his focus is also better."Read more
Well Owen is happy again, which is the biggest improvement. He is laughing and giggling again. His eye contact has improved and he is playing with toys again. All of these things had stopped. I`m so happy that he is happy. ( His Mom)Read more
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Interview with Dr. Ernesto Gutierrez from the World Stem Cells Clinic by Healthcare Elsewhere show with John Cote on iTunes!:October 13th, 2014
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