Children With Autism Are Treatable By Elizabeth Mumper, Md

BIOMEDICAL

Children with Autism

are Treatable BY ELIZABETH MUMPER, MD Dr. Mumper is the Medical Director of the Autism Research Institute and founder of the Rimland Center.

A

t the Rimland Center, we embrace the paradigm shift away from considering autism as a static encephalopathy; the new paradigm conceptualizes autisms as systems disorders affecting multiple biological processes. Such a shift in clinical direction toward detection of medical conditions which are amenable to treatments often leads to improvement in clinical symptoms, including so-called autistic symptoms. In our work, we consider medical problems common in children with autism, including intestinal pathology and gastrointestinal symptoms, allergies and autoimmunity, metabolic abnormalities, oxidative stress and impaired detoxification. As Medical Director of the Clinician Seminars associated with Defeat Autism Now!, I teach a paradigm of systemic involvement (Herbert 2005). See Figure 1. Our approach relies on a unique model of parental collaboration with clinicians and scientists. Reports from parents about their children’s symptoms and responses to treatment are helpful in formulating hypotheses, designing research projects and testing treatment strategies. Our underlying premise is that each autistic child is an individual with unique biochemical, genomic, and medical profiles. This unique approach resulted from abandoning the belief that autism is fixed prenatally and unchangeable after birth in favor of the view that many subsets of autism arise from insults which occur either before or after birth and are potentially treatable. The classic developmental literature documents the value of early intervention (Rogers 1996). Clinical experience in biomedical treatments for children with autism suggests an inherent value to beginning interventions as soon as possible after diagnosis. Numerous studies have failed in the

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quest to elucidate a specific genetic cause for autism (Rimland 2000; Herbert 2005). Therefore, we suggest considering an environmental trigger or triggers combined with a genetic susceptibility during vulnerable periods of development. Retrospective, objective reviews of home videos have confirmed developmental regressions as reported by parents (Werner and Dawson 2005). Vicious cycles identified in children with autism include: intestinal inflammation (Torrente, 2002), GI symptoms (ValicentiMcDermott, 2006), metabolic abnormalities (James, 2004), immune dysregulation with allergy/autoimmunity (Jyonouchi, 2005) and detoxification problems (Nataf, 2006). Successful medical rehabilitation of children

with autism usually requires attention to all four of these areas in addition to behavioral and educational strategies. See Figure 2. At the Rimland Center, we have a preference for avoiding atypical antipsychotic medications if possible and see significant improvements with nutritional, metabolic, immunomodulatory and detoxification strategies. We are heavily influenced by research at Hopkins that documents neuroinflammation with microglial activation in children with autism (Vargas, 2005). In the next issue, I will review the medical literature which further documents gastrointestinal, metabolic (see Figure 3), immune, detoxification and neuroinflammatory abnormalities in children with autism.

Figure 1: Concepts articulated by Martha Herbert, MD, PHD, pediatric neurologist at Harvard.

The emergence of a new autism model Older model

Newer model



 Genetically determined



 Brain based



 Hard-wired





 Behavioral treatments



Is autism a BRAIN DISORDER?

 Environmental triggers  Genetically influenced  Both brain and body  Metabolic abnormalities  play big role  Medical and behavioral  treatments  Improvements frequent;  some recoveries OR is it A DISORDER THAT AFFECTS THE BRAIN?

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ISSUE 29 2009

Vicious Cycles Food sensitivities Malabsorption

Gut inflammation

Increased oxidative stress

Abnormal intestinal permeability

Increased damage from toxins

Dysfunctional enzymes

Abnormal Methylation biochemistry

Environmental toxins

Chronic viral and fungal infections

TH1 to TH2 shift

Increased Autoimmunity and allergy

Impaired detoxification

Figure 2: Vicious cycles in some children with autism

Central Importance of Methylation/Redox Metabolic Pathways Methionine THF 5, 10 -ch2 THF

1

SAM

SAH

B12 5-CH3 THF

Purines and Thymidylate

Cellular Methylation Reactions

2

MS

SAHH

DNA SYNTHESIS

Adenosine

Key MTHFR = Methylene tetrahydrofolate reductase MS

= Methionine synthase

BHMT = Betaine-homocysteine methyltransferase SAM

= S-adenosyl methionine

Homocysteine

SAH = S-adenosyl homocysteine

Cystathionine

SAHH = S-adenosylhomocysteine hydrolase

3

Cysteine GSH GSSG

CBS

= Cystathionine beta synthase

GSH

= Glutahione (reduced)

GSSG = Oxidized glutathione

Figure 3: Methylation and transulfuration: a crucial biochemical crossroads which regulations gene expression and synthesis of neurotransmitters. Concept credited to Dr. S. Jill James.

Conflict of Interest Declaration Dr. Mumper has received lecture honoraria and administrative funding from the Autism Research Institute. Dr. Mumper has received research funding from the Autism Research Institute, the International Hyperbarics Institute and a private donor. She is a named expert in pending vaccine litigation. References Herbert, M. R. (2005). “Large brains in autism: the challenge of pervasive abnormality.” Neuroscientist 11(5): 417-40. Herbert, M. R., J. P. Russo, et al. (2006). “Autism and environmental genomics.” Neurotoxicology 27(5): 671-84.

gastrointestinal symptoms and dietary intervention.” Neuropsychobiology 51(2): 77-85. Nataf, R., C. Skorupka, et al. (2006). “Porphyrinuria in childhood autistic disorder: implications for environmental toxicity.” Toxicol Appl Pharmacol 214(2): 99-108.

autism.” Mol Psychiatry 7(4): 375-82, 334. Valicenti-McDermott, M., K. McVicar, et al. (2006). “Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease.” J Dev Behav Pediatr 27(2 Suppl): S128-36.

James, S. J., P. Cutler, et al. (2004). “Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism.” Am J Clin Nutr 80(6): 1611-7.

Rimland, B. (2000). “Secretin treatment for autism.” N Engl J Med 342(16): 1216-7; author reply 1218. Rogers, S. J. (1996). “Brief report: early intervention in autism.” J Autism Dev Disord 26(2): 243-6.

Vargas, D. L., C. Nascimbene, et al. (2005). “Neuroglial activation and neuroinflammation in the brain of patients with autism.” Ann Neurol 57(1): 67-81.

Jyonouchi, H., L. Geng, et al. (2005). “Dysregulated innate immune responses in young children with autism spectrum disorders: their relationship to

Torrente, F., P. Ashwood, et al. (2002). “Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive

Werner, E. and G. Dawson (2005). “Validation of the phenomenon of autistic regression using home videotapes.” Arch Gen Psychiatry 62(8): 889-95.

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