Scientists have identified a new subgroup of the autism spectrum disorder (ASD). Mutations to a gene known as SLC7A5, coding for a protein localised at the blood brain barrier, have been associated with the development of the condition.
ASD affects roughly 1% of the population, but many different genetic mutations can been involved in causing it, all of which are very rare. Identifying new genes linked to autism and the mechanisms by which they do so is crucial to better understand the condition. In a number of studies, finding rare monogenic forms of ASD has given scientists the opportunity to identify new treatment targets by providing a way to link genes to biological pathways.
In a previous study published in 2012, the team had already identified mutations in a gene known as BCKDK, which was linked to a reduction of branched-chain amino acids in the brain – and to neurological complications and symptoms of ASD.
"These amino acids are important for the brain, so we thought that other mutations could be involved, and so we set out to find this out," Gaia Novarino, lead author of the new study published in Cell told IBTimes UK.
Mice model and individuals with autism
Using a mouse model, the scientists found out that a deletion of the Slc7a5 gene led to atypical brain amino acid proﬁle and severe neurological abnormalities, in a similar way than mutations to BCKDK did. They also identified several patients with autistic traits. All carried mutations in the SLC7A5 gene. In both these people and in the mice, reduced levels of branched amino acids interfered with protein synthesis in neurons.
Individuals presenting the BCKDK and Slc7a5 mutations may represent a rare subgroup of ASD, with the condition caused through a same mechanism. These are severe cases of ASD, presenting classic features of autism such as impaired social skills, nonverbal communication and repetitive behaviours, but also signs of microcephaly, problems with motor coordination and seizures.
Potential for treatment
Studying this subgroup in more detail has enabled scientists to try different treatment options that could be further tested in other research. They have shown that delivering branched amino acids straight into the brain of the mice for three weeks improved their behavioural symptoms.
"I want to stress that this is a rare subgroup of autism, and that it won't lead to the discovery of a new treatment right tomorrow. However, there is evidence that it some of its downstream mechanisms are similar to other forms of autism and that we have improved symptoms in mice. So this discovery could be useful for other types of autism as well. It provides us with new ways of thinking about different types of autism, the convergence between them, and steps we can take in future research", Novarino, who works at the Institute of Science and Technology Austria, says.
While this is a promising perspective, it does not mean that these findings will be translated in clinical trials. Previous research into fragile X syndrome, which shares phenotypic similarities with certain forms of autism, has shown the limits of using mice models for rare forms of autism.
Dr Eva Loth, Sackler Lecturer in Translational Neurodevelopment at Kings College London, told IBTimes UK: "Risk genes for ASD may converge on a smaller number of common molecular pathways, so we may find treatments that target these pathways rather than specific genes. This discovery is interesting because it adds another piece to this puzzle, although the concern is that these results won't be matched in clinical trials".