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At this time there is no universally-accepted therapy or cure for autism, but stem cell therapy has been shown to improve certain parameters of the disorder. The doctors at Regenecell use a unique preparation of stem cells to address the two main pathologies implicated in autism: hypoperfusion to the brain and immune dysregulation, which has the potential to heal the brain and gastrointestinal system.

Below is a paper commissioned by Regenecell Pty Ltd, to supplement the current anecdotal data on the treatment of Autism with peer-reviewed published data relevant to umbilical cord stem cell therapy. For additional information, contact: info@regenecell.com

Potential of Stem Cell Treatments for Autism


In June of 2007 an article was published in a peer-reviewed journal (refer to: http://www.translational-medicine.com/content/5/1/30) (1) proposing a role for stem cell therapy in treating autism. The account that follows provides a perspective on the implications and prevalence of autism, as well as a synopsis and a critique of the proposed use of stem cells to treat the major symptoms of autism disorder.

Autism
Autism is a complex brain developmental disorder that is characterised by impaired social interactions, communication difficulties, obsessive attachment to routines and repetition, and often an extreme dislike of certain sounds, textures and tastes. Autism usually surfaces in the first three years of life and may vary in severity from mild to disabling. Depending on degree of severity, some children with autism may develop into independent adults with full time employment and self-sufficiency; however this is seldom the case (2). There is no known single cause but abnormalities in brain function are generally attributed to environmental, immunological and neurological factors.

Social costs
It is reported as one of the fastest-growing developmental disabilities in the US, with diagnoses having increased by staggering proportions in the last decade (2). An estimated 1.5 million children and adults in the U.S. currently (as at 2007) have some form of autism (2). Presenting these statistics another way; autism spectrum disorders are believed to affect approximately 1 in 166 children (1).

Children with autism suffer from two major conditions: Hypoperfusion and Immune Dysregulation

Hypoperfusion of the brain in autism

Children with autism have shown impaired blood flow (hypoperfusion) to the brain. Hypoperfusion may contribute to functional defects not only by inducing hypoxia (an oxygen deficit that prevents normal brain function) but also by allowing for abnormal metabolite or neurotransmitter accumulation. Hypothetically, if perfusion can be improved through the revitalisation of blood vessels (angiogenesis), then this should also allow for metabolite clearance and restoration of functionality.

Immune dysregulation in autism
Successful neurodevelopment is contingent upon a normal balanced immune response. Children with autism have immune systems that do not function normally; instead an autoimmune response of the nervous system appears to prevail (3). Astrocytes (supportive brain cells) that normally play a critical role in regulating perfusion [reviewed in 1] and protection against central nervous system infection, have the potential to cause damage to the host when functioning in an aberrant (i.e. auto-immune) manner. Autistic children often have continually suppressed immune systems and chronic inflammation. Immune dysregulation is very apparent in gastrointestinal health - most autistics experience symptoms ranging from diarrhea, gas, and bloating to intestinal lesions and inflammation of their gastrointestinal system (3,4).

Autism treatments
At this time there is no universally-accepted therapy or cure for autism. Current approaches are either behavioural, medical (treatment of anxiety and depression), nutritional (restriction of allergy-associated dietary components/ supplementation of minerals and vitamins/antioxidant therapy) or a combination of these. Research has increasingly focused on the connections between the immune system and the nervous system (4) yet to date no approach has been successful in correcting immune dysregulation/chronic inflammation in autism.

Rationale for using Stem Cells to treat autism
The administration of CD34+ umbilical cord cells and mesenchymal cells are proposed as novel treatments for the two pathologies associated with autism – hypoperfusion to the brain and immune dysregulation (1). Using these two kinds of stem cells together may potentially heal both the brain and the gut (3,4).

Treatment of hypoperfusion defect with umbilical cord blood CD34+ stem cells
Angiogenesis - the formation of collateral blood vessels - is believed to be fundamental in neurological recovery. A promising method of increasing angiogenesis into damaged areas is by administration of CD34+ stem cells [reviewed in 1]. Umbilical cord blood has highly active CD34+ cells that, following injection into a patient, should induce angiogenesis in areas of cerebral hypoperfusion. Consequently improved blood flow and oxygen to the brain should also improve nervous system functioning.
Safety: Allogeneic cord blood CD34+ cells are needed if this therapy is to be made available for widespread use because few, if any, patients will have access to autologous cord blood. Safety concerns regarding allogeneic CD34+ cells centre on fears of graft / host reactions. It is believed that allogeneic cord blood cells can not be used without immune suppression however Riordan et al (6) have recently published an account of the feasibility of cord blood cells administration in absence of immune suppression. Also, there are reports of stem cell treatments where no immune suppression was used in over 500 patients without a single one suffering graft vs. host disease [reviewed in 1].

Immune modulation by mesenchymal stem cells
The treatment of immune dysregulation in autism is expected to profoundly influence neurological function. The ability of mesenchymal stem cells to suppress pathological immune responses (e.g. inflammation) and to stimulate haematopoiesis (blood cell regeneration) leads to the possibility that these cells may also be useful for treatment of the defect in T cell numbers associated with autism(3).
Safety: The review by Ichim et al (1) suggests that allogeneic mesenchymal stem cells administered to suppress inflammation may be used without fear of immune-mediated rejection.

Practical clinical entry
The following passage is quoted directly from the authors’ proposal in ‘Stem Cell Therapy for Autism’(1) and outlines their suggestions for clinical trials : “We propose a Phase I/II study investigating a combination of cord blood expanded CD34+ cells together with mesenchymal stem cells for the treatment of autism and clinical manifestations of inflammatory intestinal disease. One of the authors (*Fabio Solano) has utilized both CD34+ and mesenchymal stem cells clinically for treatment of various diseases. In some case reports, the combination of CD34+ and mesenchymal stem cells was noted to induce synergistic effects in neurological diseases, although the numbers of patients are far too low to draw any conclusions. We propose to conduct this study based on the previous experiences of our group in this field, as well as numerous other groups that have generated anecdotal evidence of stem cell therapy for autism but have not published in conventional journals. We believe that through development of a potent clinical study with appropriate endpoints, much will be learned about the pathophysiology of autism regardless of trial outcome.”

Cautionary arguments
While the rationale for using stem cells to treat autism is indeed sound, many proponents of stem cell treatment for autism (6,7,8,9) are in agreement that clinical trials with sufficient patient numbers are needed to assess treatment efficacy. When patients and their families consider new treatments, the proposals need to be interpreted in a discerning manner that can be balanced with scientific evidence.

REFERENCES
1. Review: Stem Cell Therapy for Autism Thomas Ichim, Fabio Solano, Eduardo Glenn, Frank Morales, Leonard Smith, George Zabrecky, Neil H Riordan Journal of Translational Medicine June 2007, 5:30 http://www.translational-medicine.com/content/5/1/30
2. Alliance for stem cell research www.curesforcalifornia.com
3. The immune response in autism: a new frontier for autism research Paul Ashwood, Sharifia Wills, Judy vd Water Journal of Leukocyte Biology. 80:1–15; 2006
4. The Stem Cell and Autism Connection www.bodyecology.com
5. Autism www.stemcelltherapies.org
6. Cord blood in regenerative medicine: do we need immune suppression? Riordan N, Chan K, Marleau A, Ichim T. Journal of Translational Medicine. Jan 2007 5:8
7. www.autismvox.com/another-autism-treatment-stem-cell-therapy Kristina Chew, July 2007
8. www.cellmedicine.com (publication is equivalent to Review: Stem Cell Therapy for Autism Ichim et al.)
9. Osiris www.osiris.com



 
 
 
 
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