Tpst-assay for diagnosis of autism and related disorders

#The present invention relates to the diagnosis and treatment of autism and related disorders such as those involving language problems and obsessive compulsive traits, disease associated with food allergy, diseases commonly treated with dopamine antagonists and diseases which have an associated abnormal cholecystokinin activity.

#Autism is a pervasive developmental disorder generally characterised by withdrawal from social contact and repetitive or obsessive behavior, often with bursts of hyperactivity. Autism is characterised by a broad phenotype and attempts to define a genotype have been hindered by this fact. However, recent approaches to define sub-populations within the phenotype using personality characteristics of families hold promise for revealing associated genes. Using this strategy, associations with regions on chromosomes 7, 13 and 15 have been found which can be linked to pro-bands showing language problems (chromosomes 7 and 13) and obsessive compulsive traits (chromosome 15). High rates of duplication in 15q 11-13 are also emerging, and this region is also implicated in Angelman's syndrome. It has also been demonstrated that an over-expression of the D8/17 immune marker is particularly associated with pro-bands demonstrating obsessive compulsive traits, and this marker is also implicated in the incidence of rheumatic fever, Sydenham's Chorea, childhood-onset obsessive compulsive disorder, Tourettes syndrome and the development of tics.

#Neuro-functional abnormalities have been suggested in autism and many theories extended as explanations for the diverse symptoms of the condition. Oxytocin and vasopressin have been implicated in the neurophysiological network that regulates social affiliation and imprinting, and evidence has been collected which demonstrates an oxytocin deficiency in autism.

#The present invention will now be described, by way of example only, with reference to the following drawings, in which

#FIG. 1 shows the TPST activity in platelets from 14 autistic children compared to a pooled (n=5) control platelet sample;

#FIG. 2 shows the effect of various compounds on T?ST activity from normal human platelets and demonstrates that activity can be either stimulated or inhibited depending on the compound of choice;

#1. Assay for TPST

#The activity of sulphotransferases can be measured by monitoring the transfer of 35S from the sulphate donor, PAPS35, to the product, in this case the synthetic tyrosine substrate EAY. This assay uses platelets from control subjects (n=5) and those patients suffering from a particular disorder, selected from autism (n=14), irritable bowel syndrome (n=3) schizophrenia (gluten-sensitive)(n=4), food allergy (gluten, milk) (n=3) and depression (n=2).

#Reaction mixtures were incubated for 50 minutes at 37° C. and reactions were stopped by barium acetate. Unreacted sulphate, proteins and nucleotides were precipitated by zinc sulphate and barium hydroxide. Within the reaction there is a positive and negative control. The positive control is termed 100%, and represents the total amount of radioactivity present in the hot PAPS35 sample. The negative control is the “no-enzyme” reaction, this represents the amount of sulphate transferred to the product when no enzyme is present, i.e. the chemical reaction. The blank for the reaction is made up without PAPS35 and without enzyme.