Researchers have found both a possible reliable biomarker for diagnosing certain forms of autism and a potential therapeutic target after they identified a key signalling defect within a specific membrane structure in all cells.
Dr J Jay Gargus, Ian Parker and colleagues at the University of California, Irvine Center for Autism Research & Translation examined skin biopsies of patients with three very different genetic types of the disorder (fragile X syndrome and tuberous sclerosis 1 and 2).
They discovered that a cellular calcium signalling process involving the inositol trisphosphate receptor was very much altered.
This IP3R functional defect was located in the endoplasmic reticulum (ER), which is among the specialised membrane compartments in cells called organelles, and may underpin cognitive impairments - and possibly digestive and immune problems - associated with autism.
"We believe this finding will be another arrow in the quiver for early and accurate diagnoses of autism spectrum disorders," said Gargus, director of the Center for Autism Research & Translation and professor of pediatrics and physiology & biophysics.
"Equally exciting, it also presents a target of a molecular class already well-established to be useful for drug discovery," Gargus said.
Many of the genes associated with autism spectrum disorder (ASD) have been found to be part of the same signalling pathway, and multiple defects in this pathway may converge to produce a large functional change.
The UCI scientists detected such a convergence in the IP3R calcium channel in an organelle called the endoplasmic reticulum. Organelles are membrane structures within cells with specialised cellular functions.
According to Gargus, diseases of the organelles, such as the ER, are an emerging field in medicine, with several well-recognised neurological ailments linked to two other ones, the mitochondria and lysosomes.
The IP3R controls the release of calcium from the ER. In the brain, calcium is used to communicate information within and between neurons, and it activates a host of other cell functions, including ones regulating learning and memory, neuronal excitability and neurotransmitter release - areas known to be dysfunctional in ASD.
"We propose that the proper function of this channel and its signalling pathway is critical for normal performance of neurons and that this signalling pathway represents a key 'hub' in the pathogenesis of ASD," said Parker, a fellow of London's Royal Society and UCI professor of neurobiology & behaviour, who studies cellular calcium signalling.
To see if IP3R function is altered across the autism spectrum, clinical researchers at the Center for Autism & Neurodevelopmental Disorders - which is affiliated with the Center for Autism Research & Translation - are currently expanding the study and have begun to examine children with and without typical ASD for the same signalling abnormalities.