Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
We propose a study which will combine multiple modalities in evaluating the treatment
 response of children with autism spectrum disorders (ASD) to acetyl-choline esterase (AChE)
 inhibitors and choline supplements. The primary objective of the study is to examine the
 efficacy of this treatment in improving core autistic symptoms. The Secondary objective of
 the study is to evaluate the safety and tolerability of the treatment protocol in ASD
 children. Exploratory objectives include evaluation of the influence of the treatment on
 linguistic performance, comorbid behaviors, adaptive functioning and executive functions.
Autism Spectrum Disorders (ASD) are a group of developmental disorders of brain function
 resulting in a distinct phenotype, most probably related to many specific causes. Individuals
 with a disorder in the autism spectrum are a heterogeneous group of patients with early
 childhood onset of deficits in social interaction, communication and language, and repetitive
 and stereotypic behaviors. ASD has become increasingly prevalent during the last few decades
 (Wiznitzer, 2005).

 The neuro-anatomical substrate of ASD has been the subject of intense investigation, but
 current findings are inconclusive, limited and sometimes even contradictory.

 Medical treatment of autism is still a matter of dispute. Medications used are mainly aimed
 to treat the comorbid symptoms, such as epilepsy, tics, obsessive-compulsive or hyperactive
 behaviors (Wiznitzer, 2005). Although many efforts were invested in establishing a model of
 autistic pathophysiology, no such model is currently accepted, and there is no evidence for
 an efficient treatment of the core autistic symptoms (Wiznitzer, 2005).

 Previous studies indicate that many brain systems are involved in the expression of autism.
 Specifically, it has been suggested that autism involves neurotransmitter dysregulations (Lam
 et al, 2006). A recent investigation of the cholinergic system in autism, detailed below, has
 provided promising findings. Our study aims to assess the clinical outcomes associated with
 cholinergic manipulations using pharmacological agents and nutritional supplements. The study
 approved by the Helsinki committee for clinical research.
Inclusion criteria:

 -  A formal diagnosis of Autism or Pervasive Developmental Disorder not otherwise
 specified (PDD-NOS), given by a child neurologist.

 -  Age: 10-18 years.

 -  A signed parental consent form.

 Exclusion criteria:

 -  Evidence for one of the following conditions:

 -  an underlying infectious disease

 -  chromosomal abnormality

 -  metabolic disorder

 -  specific brain related disorder (such as tuberous sclerosis)

 -  history of fetal cytomegalovirus infection

 -  birth asphyxia

 -  a history of major head injury

 -  a chronic use of non-steroidal anti-inflammatory drugs, (NSAID)

 -  known brain damage

 -  Epilepsy

 -  Abnormal Electro-cardiogram (ECG)

 -  Epileptiform EEG

 -  Use of psychostimulants, anti-depressants, neuroleptics or anti-convulsive agents
 within the past month.

 -  Lack of cooperation in the screening phase