Other typical behaviors may include resistance to change and insisting on the same daily activities or eating habits.
According to estimates from the Centers for Disease Control and Prevention and from the Autism and Developmental Disabilities Monitoring (ADDM) Network, about 1 in 68 children has been identified with autism spectrum disorder (ASD). ASD is found to be almost 5 times more common among boys (1 in 42) than among girls (1 in 189). Studies in Asia, Europe, and North America have identified individuals with ASD with an average prevalence of about 1%. It is estimated to cost between $17,000 and $21,000 extra for health care, education, ASD-related therapy, family-coordinated services, and caregiver time for a child with ASD compared to a child without ASD and about $40,000 and $60,000 per child per year on the autistic behavior therapies.
Causes of Autism
The majority of the evidence suggests that ASD represents a complex relationship between exposure to environmental stressors and genetic susceptibilities. There is substantial evidence that autism is the result of genetic defects. Studies have shown that there is an increased risk of autism found in younger siblings of the children with the disorder. Several genes have been implicated in the process, however, researchers have not been able to identify the exact genes involved.
Several contributory factors are proposed to be associated with the condition, including advancing parental age at time of conception; premature birth (before 35 weeks of pregnancy); defective blood–brain barrier; exposure to alcohol, cocaine, or medications such as sodium valproate, misoprostol, or thalidomide; perinatal infections such as congenital rubella; or CMV, in-utero hypoxia, or defective immune response to other viral or bacterial agents. Thimerosal (a preservative used in vaccines) and Measles-Mumps-Rubella (MMR) vaccination has been postulated in relation to the causation of autism, but there is no convincing evidence to support this claim.
Other proposed associations of autism may include mitochondrial defects with oxidative stress, defective glutathione pathway and heavy metal metabolism pathways, and environmental exposure to specific factors. Tuberous sclerosis, fragile X syndrome, and other medical conditions are seen along with autism or are proposed to have a link in the causation of the condition. Thus, autism is a result of the complex combination of genetic, environmental, and immunological factors.
It has recently been suggested that autism is associated with hypo-perfusion of the brain and immune system dysregulation resulting in pathological changes causing defects in cognition, language, and other neurophysiological changes associated with the condition. Hypoxic necrosis of the neurons result in abnormal metabolism and an increased accumulation of the neurotransmitters. Immune system irregularities cause cellular imbalance and elevated levels of pro-inflammatory cytokines. The severity of the symptoms correlates with increased damage to the brain and an incremental deterioration of the immune system.
The defective areas of the brain implicated for autism are the cerebral cortex, including the temporal and frontal lobes, the limbic system, the amygdala and hippocampus, and the cerebellum. Abnormal neural patterning and defects in excitation and inhibition in the neural system are found to contribute to the various symptoms of the condition along with the dysregulation in serotonin and glutamatergic and GABAergic neurotransmission. Abnormality in brain growth regulation results in overgrowth of the brain during early childhood, followed by a more slow growth, as compared to the normal children.
Treatment Strategies for Autism and Role of Stem Cells
There is no cure for autism or other developmental disorders, and usually lifelong management is required. The primary aim of treatment is to improve the quality of life and to curtail the deficits and problems associated with the condition. There is no standard therapy for autism, however, the current treatment options can be divided into educational, medical, and nutritional therapies.
Various educational modalities are implied to enhance communication and social skills and to minimize maladaptive behaviors. Special consideration must be considered for the treatment of health conditions associated with autism. Medications such as antipsychotics, antidepressants, and stimulants have been shown to improve various clinical symptoms and behaviors in ASD.
Complementary (alternative) medicine practices and several non-FDA-approved nutritional supplements are also being used widely as therapy, however, much scientific research is needed to further evaluate the rationalized guidelines for treatment.
Stem cell technology can be useful to better understand complex multifactorial diseases like ASD. Stem cells have been used to create disease models at the cellular levels in laboratories to understand pathogenesis. Researchers are also looking for opportunities to apply technologies to treat these conditions. Researchers from China, India, and Mexico have reported the use of stem cells and growth factor injections for the treatment of autism, but the benefits of these treatments are highly doubtful because no rigorous clinical trials have been performed. A better understanding of the pathology of this disease and randomized, controlled clinical trials are necessary before the promise of stem cell research is realized in this area.
Stem cells are also being used in disease modeling. Induced pluripotent stem cells (iPSCs) have successfully been used for the modeling of complex diseases. Autism cells have been recreated in labs by differentiation of human iPSCs to study the pathogenesis of the disease at the cellular level. Induced pluripotent stem cells derived from individual patients will help better understand genomic and structural variations of the disease condition, thereby providing opportunities for better screening and development of treatment.
Stem cells and iPSC technologies are still in their infancy. It is still unclear whether these technologies can be useful to model complex multifactorial conditions like autism, which are caused by various genetic and environmental factors and their interaction in a complex organ like the brain. Also hindering the technology is the fact that the autistic etiology is variable in its presentation, complicating the validation of cellular models.
Mudassir Farooqui
Aga Khan University Hospital
See Also: Cord Blood Stem Cells; Clinical Trials, U.S.: Immunologic/Histiocytic Disorders; Mesenchymal Stem Cells.
Further Readings
Aigner, Stefan, Tobias Heckel, Jitao D. Zhang, et al. “Human Pluripotent Stem Cell Models of Autism Spectrum Disorder: Emerging Frontiers, Opportunities, and Challenges Towards Neuronal Networks in a Dish.” Psychopharmacology, v.231 (2014).
Centers for Disease Control and Prevention. http://www.cdc.gov/ncbddd/autism/data.html (Accessed May 21, 2015).
DeRosa, B. A., J. M. Van Baaren, G. K. Dubey, et al. “Derivation of Autism Spectrum Disorder-Specific Induced Pluripotent Stem Cells From Peripheral Blood Mononuclear Cells.” Neuroscience Letters, v.10 (May 2012).
Ichim, Thomas E., Fabio Solano, Eduardo Glenn, et al. “Stem Cell Therapy for Autism.” Journal of Translational Medicine, 2007, v.5/30 (2007).
Kim, K.-Y., Yong Wook Jung, Gareth J. Sullivan, et al. “Cellular Reprogramming: A Novel Tool for Investigating Autism Spectrum Disorders.” Trends in Molecular Medicine, v.18 (2012).
Kong, Xuejun, Xiaochun Wang, and William Stone. “Prospect of Stem Cell Therapy for Autism Spectrum Disorders.” North American Journal of Medical Science, v.4/3 (July 25, 2011).
Marchetto, Maria C. N., Beate Winner, and Fred H. Gage. “Pluripotent Stem Cells in Neurodegenerative and Neurodevelopmental Diseases.” Human Molecular Genetics, v.19 (2010).
Siniscalco, Dario, James Jeffrey Bradstreet, and Nicola Antonucci. “Therapeutic Role of Hematopoietic Stem Cells in Autism Spectrum Disorder-Related Inflammation.” Frontiers in Immunology, v.4 (2013).
Stem Cell Institute. http://www.cellmedicine.com/autism-and-stem-cell-publications/