US 12,522,871 B2 · Expression-based diagnosis, prognosis and treatment of complex diseases

Abstract

The invention provides for the detection of a perturbed gene network, which includes highly expressed genes during fetal brain development, which is dysregulated in neuron models of autism spectrum disorder (ASD). High-confidence ASD risk genes are upstream regulators of the network modulating RAS/ERK, PI3K/AKT, and WNT//β-catenin signaling pathways. The invention demonstrates how the heterogeneous genetics of ASD can dysregulate a core network to influence brain development at prenatal and very early postnatal ages and, thereby, the severity of later ASD symptoms. The invention provides a model for diagnosis, prognosis determination, and optionally treatment and monitoring, for any disease by comparing molecular marker patterns in non-affected tissues in a subject with healthy controls to determine a dysregulated network in the subject based on a co-expression pattern of interacting genes.

Claims17

Dependent claims

A method of treating autism spectrum disorder (ASD) in a subject comprising:

a. obtaining a prenatal or early postnatal (<1 year old) biological sample of the subject;
b. measuring leukocyte gene expression patterns of more than two molecular markers in the biological sample, wherein the markers include at least one gene selected from each of RAS/ERK, PI3K/AKT and WNT/β-catenin pathways;
c. comparing the molecular marker patterns with healthy controls for gene regulatory mechanisms, signaling pathways and protein interactions to identify, in the subject, a first subtype of ASD or a second subtype of ASD based on a co-expression pattern of one or more pairs of interacting genes in a dysregulated network showing elevated gene co-expression activity in the RAS/ERK, PI3K/AKT and WNT/β-catenin pathways;
d. determining, based at least in part on the first subtype of ASD being identified in the subject, an effective disease therapy for the subject;
and
e. administering the effective disease therapy to the subject.

3 more elements

Dependencies are inferred from the claim text.

Expression-based diagnosis, prognosis and treatment of complex diseases

Life of this patent

Expression-based diagnosis, prognosis and treatment of complex diseases

Life of this patent

Abstract

Claims17