Biomarker assay for use in monitoring autism

Abstract

The present invention relates to protein kinase A (PKA) for use in diagnosing autism spectrum disorder (ASD) phenotype 1 in an ASD patient wherein PKA levels are measured in a sample of the patient and wherein ASD phenotype 1 is diagnosed if the measured levels are lower than PKA levels in an age and sex-matched control sample. Additionally, the present invention relates to PKA for use in monitoring variation in ASD severity in an ASD patient, wherein PKA levels are measured in a sample of the patient and an increase in ASD severity is characterized by a decrease of PKA levels compared to PKA levels measured in previous samples of the patient. The present invention also relates to PKA for use in monitoring efficacy of an ASD treatment in an ASD phenotype 1 patient, wherein PKA levels are measured in a sample of the patient and wherein a positive response to the ASD treatment is characterized by an increase of PKA levels in comparison to baseline PKA levels of the patient prior to treatment. Furthermore, the present invention is directed to methods of diagnosing ASD phenotype 1 as well as kits comprising means to measure PKA levels.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a biomarker assay for use in monitoring autism spectrum disorders (ASD), in particular ASD phenotype 1. Furthermore, the assay of the invention is also useful for diagnosing ASD phenotype 1.BACKGROUND OF THE INVENTION[0002]The cAMP-dependent protein kinase (PKA) is activated by the binding of cAMP to the regulatory subunit (R), of the molecule and results in the release of the active catalytic kinase subunit (C). Most of the effects of cAMP in eukaryotic systems are the result of phosphorylation of proteins at serine or threonine residues by PKA. There are several isoforms of both subunits of PKA. PKA is localized subcellularly by binding to multidomain scaffolding proteins known as AKAPs which bind to the R subunits of the holoenzyme (Pearce, L. R., D. Komander, and D. R. Alessi, The nuts and bolts of AGC protein kinases. Nat Rev Mol Cell Biol, 2010. 11 (1): p. 9-22). PKA plays a key role in neurodevelopment.[0003]Autism ...

AI Technical Summary

Benefits of technology

The present invention provides a method for diagnosing autism spectrum disorder (ASD) using protein kinase A levels in a patient sample. By measuring protein kinase A levels and comparing them to those of a control sample, a diagnosis of ASD phenotype 1 can be made if the measured protein kinase A levels are lower than those of the control sample. Additionally, the invention provides a method for monitoring the severity of ASD in a patient sample by measuring protein kinase A levels and comparing them to previous samples. Finally, the invention provides a method for monitoring the effectiveness of a treatment for ASD in a patient sample by measuring protein kinase A levels.

Problems solved by technology

. . ) or comorbidities such as epilepsia can also result in a worsening of symptoms.

However, there is a growing recognition by the scientific community that the behavioral based DSM-5 diagnosis of ASD does not allow for reasonable classification in terms of molecular and genetic alterations, but rather serves as a behavior based umbrella term for a large group of disorders with different etiology.

However, these strategies face difficulty encompassing the genetic and phenotypic heterogeneity of ASD, and may not assist in the identification of specific neurobiological pathways underlying disease.

However, because of the intrinsic complexity of ASD—and the complex intertwining of genetic and environmental causal factors, specific biomarkers for ASD have yet to be identified which could be used to establish such an assay.