This invention is in the field of medical molecular diagnostics. It provides methods and means for the in vitro detection of the neurodevelopmental toxicity of a compound by determining the gene expression of a limited number of genes. More in particular, it relates to a method for determining the likelihood that a compound is neurodevelopmental toxic, comprising the steps of: providing embryonic stem cells, allowing the stem cells to form embryoid bodies, allowing the embryoid bodies to differentiate into neural cells, in the presence of said compound, thereby creating a neural differentiation culture, extracting total RNA from the cells in said neural differentiation culture, determining the expression levels of genes Hoxb6, Nrk, 1700011H14Rik and Tph1, comparing the expression levels with a predetermined reference value and determining the increase or decrease of the expression level relative to the reference value, wherein a relative increase or decrease in expression value of more than 20% indicates that a compound is neurodevelopmental toxic.

The present invention provides a method for assessing embryotoxicity of a chemical comprising: (1) a first step of measuring the expression level of one or more genes selected from among genes each comprising any of the nucleotide sequences of SEQ ID NOs: 1 to 78 and 101 to 230 and orthologous genes thereof in a sample from a non-human mammal or mammalian cell which has come into contact with a test chemical; and (2) a second step of comparing the measured value of the expression level of the gene in the sample obtained in the first step with a control value of the expression level of the gene and based on the difference assessing the level of the embryotoxicity of the test chemical in the sample; and so on.

Described herein are compounds useful for the treatment and investigation of diseases, methods for the prediction of in vivo toxicity of compounds useful for the treatment and investigation of diseases, and methods of discovering and identifying compounds useful for the treatment and investigation of diseases that have reduced in vivo toxicity.

The present invention is directed to methods for detecting the presence of minimal or early vasculitis or other vasculopathies induced by a cox-2 inhibitor in a subject to whom a cox-2 inhibitor has been administered, selection of cox-2 inhibitory compounds, use of a cox-2 inhibitory compounds in the manufacture of anti-inflammatory medicaments, and vaccination strategies.

Provided are assay systems for determining the therapeutic or toxic effect of a putative drug based on assaying its activity in cells which have been differentiated in vitro from stem cells, and induced to display a phenotype that resembles a disease to be treated.

In one aspect, the present invention features a method of inhibiting proliferation and/or reducing survival of a cell comprising a GNAQ polynucleotide or polypeptide having a R183Q or Q209L mutation, comprising contacting the cell with puromycin or a puromycin analog, thereby inhibiting proliferation and/or reducing survival of the cell. In another aspect, a method of treating a vascular malformation or related condition in a subject, comprising administering to the subject an effective amount of puromycin or a puromycin analog is featured. In another aspect, the present invention features a method of identifying a candidate agent that modulates a GNAQ R183Q or Q209L mutation-associated disease, comprising contacting a cell comprising a GNAQ polynucleotide or polypeptide having a R183Q or Q209L mutation with puromycin and a candidate agent and comparing viability of the contacted cell with a reference level of viability, wherein an alteration in viability indicates that the candidate agent modulates the GNAQ R183Q or Q209L mutation-associated disease.

The present disclosure provides for characterization of normal flora and identifying biomarkers in the gut of healthy, neruotypical subjects. Aspect of the disclosure provide for the characterization of the gut microbiome in ADS subjects, characterized by reduced richness and significant loss of the ‘Prevotella-like enterotype’ compared to neurotypical subjects. The relative abundance of genera Prevotella, Coprococcus, Prevotellaceae and Veillonellaceae are significantly lower in autistic children than in neurotypical children. Further, Prevotella, is one of the three main classifiers for the human enterotypes, along with Bacteroides and Ruminococcus. These three core genera are among main contributors in the principle component analysis. ‘Prevotella-like enterotype’ was absent in the autistic group, while neurotypical samples showed an even distribution among the three enterotypes. The present disclosure provides for an understanding the association between gut microbiota, health, and disease states, and provides for potential diagnostic and therapeutic targets.

A novel method to predict toxicity and dose-dependent effects of an agent based on transcriptomic data analysis, by determining a predictive toxicogenomics space (PTGS) score. The PTGS score helps to predict and model the toxicity of compounds typically consisting of chemicals, pharmaceuticals, cosmetics and agrochemicals. The invention further comprises methods of deriving the PTGS score, as well as computer programs to calculate PTGS scores.

The invention provides epsilon toxin (ETX) produced by Clostridium perfringens type B or type D as a causative toxin for human multiple sclerosis (MS). The invention further identifies ETX binding receptor MAL for ETX mediated cell death and other toxin-logical activities in MS. Methods and compositions to prevent humans from multiple sclerosis (MS) and/or treating MS by directly or indirectly interfering with epsilon toxin (ETX), its binding receptor (e.g., MAL), or ETX-receptor interactions so as to inhibit or suppress downstream ETX mediated receptor signaling activities are provided. Also provided are various methods to detect, diagnose, monitor, assess multiple sclerosis (MS) by determining an expression level of ETX gene or its encoding protein in human patient suspected for and/or at risk for multiple sclerosis (MS).

The present invention relates to in vitro methods for the determination of the potential toxicity of test compounds. The invention also comprises in vitro methods for the selection of therapeutical compounds useful for the treatment of pathology related to an alteration of the mechanism of the mRNA editing of ADAR dependent A to I mRNA editing of the serotonin 2C receptor (5HTR2C). Finally, the present invention is directed to the kits and tools for the implementation of these methods. The invention is of special utility in the pharmaceutical industry for analysis of the toxicity profile or the screening of compounds involved in drug development and/or in pharmaceutical compositions.