| Potential of Stem Cell Treatments for Autism | | | | of CD34+ stem cells [reviewed in 1]. Umbilical cord |
| In June of 2007 an article was published in a | | | | blood has highly active CD34+ cells that, following |
| peer-reviewed journal (1) proposing a role for stem | | | | injection into a patient, should induce angiogenesis in |
| cell therapy in treating autism. The account that | | | | areas of cerebral hypoperfusion. Consequently |
| follows provides a perspective on the implications and | | | | improved blood flow and oxygen to the brain should |
| prevalence of autism, as well as a synopsis and a | | | | also improve nervous system functioning. |
| critique of the proposed use of stem cells to treat | | | | |
| the major symptoms of autism disorder. | | | | Safety: Allogeneic cord blood CD34+ cells are needed |
| Autism | | | | if this therapy is to be made available for widespread |
| Autism is a complex brain developmental disorder | | | | use because few, if any, patients will have access to |
| that is characterised by impaired social interactions, | | | | autologous cord blood. Safety concerns regarding |
| communication difficulties, obsessive attachment to | | | | allogeneic CD34+ cells centre on fears of graft / host |
| routines and repetition, and often an extreme dislike | | | | reactions. It is believed that allogeneic cord blood cells |
| of certain sounds, textures and tastes. Autism usually | | | | can not be used without immune suppression |
| surfaces in the first three years of life and may vary | | | | however Riordan et al (6) have recently published an |
| in severity from mild to disabling. Depending on | | | | account of the feasibility of cord blood cells |
| degree of severity, some children with autism may | | | | administration in absence of immune suppression. |
| develop into independent adults with full time | | | | Also, there are reports of stem cell treatments |
| employment and self-sufficiency; however this is | | | | where no immune suppression was used in over 500 |
| seldom the case (2). There is no known single cause | | | | patients without a single one suffering graft vs. host |
| but abnormalities in brain function are generally | | | | disease [reviewed in 1]. |
| attributed to environmental, immunological and | | | | Immune modulation by mesenchymal stem cells |
| neurological factors. | | | | The treatment of immune dysregulation in autism is |
| Social costs | | | | expected to profoundly influence neurological function. |
| It is reported as one of the fastest-growing | | | | The ability of mesenchymal stem cells to suppress |
| developmental disabilities in the US, with diagnoses | | | | pathological immune responses (e.g. inflammation) and |
| having increased by staggering proportions in the last | | | | to stimulate haematopoiesis (blood cell regeneration) |
| decade (2). An estimated 1.5 million children and adults | | | | leads to the possibility that these cells may also be |
| in the U.S. currently (as at 2007) have some form of | | | | useful for treatment of the defect in T cell numbers |
| autism (2). Presenting these statistics another way; | | | | associated with autism(3). |
| autism spectrum disorders are believed to affect | | | | Safety: The review by Ichim et al (1) suggests that |
| approximately 1 in 166 children (1). | | | | allogeneic mesenchymal stem cells administered to |
| Children with autism suffer from two major | | | | suppress inflammation may be used without fear of |
| conditions: Hypoperfusion and Immune Dysregulation | | | | immune-mediated rejection. |
| Hypoperfusion of the brain in autism | | | | Practical clinical entry |
| Children with autism have shown impaired blood flow | | | | The following passage is quoted directly from the |
| (hypoperfusion) to the brain. Hypoperfusion may | | | | authors' proposal in ‘Stem Cell Therapy for |
| contribute to functional defects not only by inducing | | | | Autism'(1) and outlines their suggestions for clinical |
| hypoxia (an oxygen deficit that prevents normal brain | | | | trials : "We propose a Phase I/II study investigating a |
| function) but also by allowing for abnormal metabolite | | | | combination of cord blood expanded CD34+ cells |
| or neurotransmitter accumulation. Hypothetically, if | | | | together with mesenchymal stem cells for the |
| perfusion can be improved through the revitalisation | | | | treatment of autism and clinical manifestations of |
| of blood vessels (angiogenesis), then this should also | | | | inflammatory intestinal disease. One of the authors |
| allow for metabolite clearance and restoration of | | | | (*Fabio Solano) has utilized both CD34+ and |
| functionality. | | | | mesenchymal stem cells clinically for treatment of |
| Immune dysregulation in autism | | | | various diseases. In some case reports, the |
| Successful neurodevelopment is contingent upon a | | | | combination of CD34+ and mesenchymal stem cells |
| normal balanced immune response. Children with | | | | was noted to induce synergistic effects in |
| autism have immune systems that do not function | | | | neurological diseases, although the numbers of |
| normally; instead an autoimmune response of the | | | | patients are far too low to draw any conclusions. We |
| nervous system appears to prevail (3). Astrocytes | | | | propose to conduct this study based on the previous |
| (supportive brain cells) that normally play a critical role | | | | experiences of our group in this field, as well as |
| in regulating perfusion [reviewed in 1] and protection | | | | numerous other groups that have generated |
| against central nervous system infection, have the | | | | anecdotal evidence of stem cell therapy for autism |
| potential to cause damage to the host when | | | | but have not published in conventional journals. We |
| functioning in an aberrant (i.e. auto-immune) manner. | | | | believe that through development of a potent clinical |
| Autistic children often have continually suppressed | | | | study with appropriate endpoints, much will be |
| immune systems and chronic inflammation. Immune | | | | learned about the pathophysiology of autism |
| dysregulation is very apparent in gastrointestinal | | | | regardless of trial outcome." |
| health - most autistics experience symptoms ranging | | | | Cautionary arguments |
| from diarrhea, gas, and bloating to intestinal lesions | | | | While the rationale for using stem cells to treat |
| and inflammation of their gastrointestinal system | | | | autism is indeed sound, many proponents of stem cell |
| (3,4). | | | | treatment for autism (6,7,8,9) are in agreement that |
| Autism treatments | | | | clinical trials with sufficient patient numbers are |
| At this time there is no universally-accepted therapy | | | | needed to assess treatment efficacy. When patients |
| or cure for autism. Current approaches are either | | | | and their families consider new treatments, the |
| behavioural, medical (treatment of anxiety and | | | | proposals need to be interpreted in a discerning |
| depression), nutritional (restriction of | | | | manner that can be balanced with scientific evidence. |
| allergy-associated dietary components/ | | | | REFERENCES |
| supplementation of minerals and vitamins/antioxidant | | | | 1. Review: Stem Cell Therapy for Autism Thomas |
| therapy) or a combination of these. Research has | | | | Ichim, Fabio Solano, Eduardo Glenn, Frank Morales, |
| increasingly focused on the connections between the | | | | Leonard Smith, George Zabrecky, Neil H Riordan |
| immune system and the nervous system (4) yet to | | | | Journal of Translational Medicine June 2007, 5:30 |
| date no approach has been successful in correcting | | | | 2. Alliance for Stem Cell Research |
| immune dysregulation/chronic inflammation in autism. | | | | 3. The immune response in autism: a new frontier for |
| Rationale for using Stem Cells to treat autism | | | | autism research Paul Ashwood, Sharifia Wills, Judy vd |
| The administration of CD34+ umbilical cord cells and | | | | Water Journal of Leukocyte Biology. 80:1–15; |
| mesenchymal cells are proposed as novel treatments | | | | 2006 |
| for the two pathologies associated with autism – | | | | 4. The Stem Cell and Autism Connection |
| hypoperfusion to the brain and immune dysregulation | | | | 5. Autism: stemcelltherapies.org |
| (1). Using these two kinds of stem cells together | | | | 6. Cord blood in regenerative medicine: do we need |
| may potentially heal both the brain and the gut (3,4). | | | | immune suppression? Riordan N, Chan K, Marleau A, |
| Treatment of hypoperfusion defect with umbilical | | | | Ichim T. Journal of Translational Medicine. Jan 2007 5:8 |
| cord blood CD34+ stem cells | | | | 7. Kristina Chew, July 2007 |
| Angiogenesis - the formation of collateral blood | | | | 8. (publication is equivalent to Review: Stem Cell |
| vessels - is believed to be fundamental in neurological | | | | Therapy for Autism Ichim et al.) |
| recovery. A promising method of increasing | | | | 9. |
| angiogenesis into damaged areas is by administration | | | | |