Autism affects 1？:？88 children in the United States. Familial history of autoimmune disease, autoantibodies in the serum of mothers when there is more than one autistic offspring, and neuroglial response in CSF and brain tissue in autistic patients suggest an immunological variable may be associated with this condition. Lenalidomide has the potential to invoke changes in TNF-α with less toxicity than thalidomide. This pilot study evaluated lenalidomide at reduction of TNF-α and improvement of behavior and language in children with autism with elevated TNF-α. Subjects with elevated TNF-α were given 2.5？mgs lenalidomide daily for 12-weeks. Pharmacodynamics and safety was evaluated. Changes in language and autistic behaviors after six and twelve weeks were measured. Although statistical significance was not achieved for most measures, there were trends toward improvement. After 6-weeks, mean receptive language increased: 60.67 ± 12.06 to 65.00 ± 15.10 (P = 0.11) and symptoms of autism decreased (40.75 ± 5.96 versus 38.67 ± 7.90, P = 0.068). After 12-weeks, CSF-TNF-α declined 57% ± 25% from 80.5 ± 41.03 to 38.0 ± 31.27 (P = 0.068). Serum TNF-α declined 57% (92.50 ± 68.92 to 40.25 ± 44.53 (P = 0.048). This study suggests that lenalidomide is tolerated as a treatment by children with autism and should be further studied as a potential agent for cytockine inflammation. 1. Introduction Autism is currently the leading cause of developmental disability in the United States and most other countries of the world. The condition currently affects 1 in 88 children born in the United States as of 2010 [1]. Autism is best defined as a spectrum of heterogeneous developmental disabilities mainly involving three core aspects of behaviors: (1) speech and communication; (2) social interest and interaction; (3) stereotypic behaviors or mannerisms [2]. Historically, the incidence of autism has increased; however, debate exists as to whether this reflects simple population growth, recategorization and increased recognition, or whether there is a true increase in the percent of the population affected [3]. Despite this controversy, most experts and the general population agree that the incidence of autism has greatly increased, especially in states such as California which has shown a massive increase of 600% for autistic children in state educational records over two decades [4–6]. There is currently no agreed upon single genetic or other etiological risk factor that has been shown to cause autism in isolation. Current thinking is that multiple risk factors such as familial,
References
[1]
J. Baio, “Prevalence of autism spectrum disorders-autism and developmental disabilities monitoring network, 14 sites, United States, 2008,” MMWR Surveillance Summaries, vol. 61, no. 3, pp. 1–19, 2012.
[2]
American Psychological Association, Diagnostic and Statistical Manual of Mental Disorders, Skyscape, Washington, DC, USA, 4th edition, 1994.
[3]
P. T. Shattuck, “The contribution of diagnostic substitution to the growing administrative prevalence of autism in US special education,” Pediatrics, vol. 117, no. 4, pp. 1028–1037, 2006.
[4]
A. Cavagnaro, Autistic Spectrum Disorders: Changes in the California Caseload An Update: June 1987–June 2007, Department of Developmental Services, Sacramento, Calif, USA.
[5]
L. A. Croen, J. K. Grether, J. Hoogstrate, and S. Selvin, “The changing prevalence of autism in california,” Journal of Autism and Developmental Disorders, vol. 32, no. 3, pp. 207–215, 2002.
[6]
M.I.N.D. Institute, Report to the Legislature on the Principle Findings from the Epidemiology of autism in California, University of California, Davis, Sacramento, Calif, USA, 2002.
[7]
M. G. Chez, T. Dowling, P. B. Patel, P. Khanna, and M. Kominsky, “Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children,” Pediatric Neurology, vol. 36, no. 6, pp. 361–365, 2007.
[8]
A. M. Connolly, M. Chez, E. M. Streif et al., “Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy,” Biological Psychiatry, vol. 59, no. 4, pp. 354–363, 2006.
[9]
D. L. Vargas, C. Nascimbene, C. Krishnan, A. W. Zimmerman, and C. A. Pardo, “Neuroglial activation and neuroinflammation in the brain of patients with autism,” Annals of Neurology, vol. 57, no. 1, pp. 67–81, 2005.
[10]
C. A. Pardo, D. L. Vargas, and A. W. Zimmerman, “Immunity, neuroglia and neuroinflammation in autism,” International Review of Psychiatry, vol. 17, no. 6, pp. 485–495, 2005.
[11]
A. W. Zimmerman, S. L. Connors, K. J. Matteson et al., “Maternal antibrain antibodies in autism,” Brain, Behavior, and Immunity, vol. 21, no. 3, pp. 351–357, 2007.
[12]
R. Brownell, Receptive One-Word Picture Vocabulary Test (ROWPVT), Academic Therapy Publications, ATP Assessments, High Noon Books, Arena Press, Ann Arbor, Mich, USA, 2000.
[13]
R. Brownell, Expressive One-Word Picture Vocabulary Test (EOWPVT), Academic Therapy Publications, ATP Assessments, High Noon Books, Arena Press, Ann Arbor, Mich, USA, 2000.
[14]
C. Lord, R. Rutter, P. C. DiLavore, and S. Risi, Autism Diagnostic Observation Schedule (ADOS), Western Psychological Services, Los Angeles, Calif, USA, 2002.
[15]
E. Schopler, R. L. Reichler, and B. R. Renner, Childhood Autism Rating Scale (CARS), Western Psychological Services, Los Angeles, Calif, USA, 1988.
[16]
W. Guy, Assessment Manual for Psychopharmacology, National Institute of Mental Health. US Department of Health Education and Welfare, Rockville, Md, USA, 1976.
[17]
P. Patterson, “Pregnancy, immunity, schizophrenia, and autism,” Engineering Science, vol. 69, pp. 10–21, 2006.
[18]
P. H. Patterson, Modeling Features of Autism in Animals, Taylor and Francis, Boca Raton, Fla, USA, 2005.
