The study focuses on epigenetics, the study of changes in the action of human genes caused by molecules that regulate when, where and to what degree our genetic material is activated, rather than focusing on genetic changes in the DNA code we inherit from our parents.
While scientists have traditionally focused on finding individual genes responsible for Autism Spectrum Disorders (ASD), recent research has found links between epigenetic regulation and ASD in human patients. Such regulation derives, in part, from the function of specialized protein complexes that bind to specific DNA sequences and either encourage or shut down the expression of a given gene.
The researchers found that BETs, a family of epigenetic regulators that bind to many different genes and contribute to the copying of these genes into messenger RNA, the template used by the cell to make proteins, play a key role in the regulation of normal neuronal development and function. The Mount Sinai study was conducted using a new type of pharmacological compound that does not inactivate BET proteins but, rather, prevents them from binding to the genes.
The research team developed a novel, highly specific, brain-permeable inhibitor of BET proteins called I-BET858. The compound was initially tested on in vitro cultured mouse neurons. The researchers found that it affected the function of a particular group of genes with known links to neuron development and synaptic functions. Importantly a significant number of the affected genes have been linked to ASD in humans.
Subsequently, the study team evaluated the effect of I-BET858 when injected into mice. They found the compound was able to trigger selective changes in neuronal gene expression in the brain followed by development of an ASD-like syndrome