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In-vivo MRS assay of brain glutamate-GABA balance and drug response in autism

United Kingdom

Treating Autism Spectrum Disorder (ASD) is a challenge as the causes are unknown and the biological diversity of the patient population is very large. However, recent studies indicate that ASD may involve a disturbance in the balance of excitatory (glutamate) and inhibitory (GABA) brain chemicals, suggesting that the glutamate/GABA system offers a treatment target for ASD. For the first time in humans with and without ASD, this project will measure baseline brain glutamate and GABA levels and the response to an anti-glutamate drug, Riluzole, using in-vivo magnetic resonance spectroscopy (MRS). Riluzole, is a drug which blocks glutamate release from neurons, and which shows early promise in treatment of ASD. The prediction is that Riluzole will act to restore the glutamate/GABA imbalance towards control levels. This study is likely to provide evidence that the glutamate/GABA system may be a dynamic biomarker for ASD, against which drugs can be targeted and individual response to treatment measured. In addition, this project will promote the application of MRS to identify subgroups of patients likely to respond to a particular drug prior to treatment, thereby tailoring treatment to the individual. Finally, if successful, this work will lead directly to further studies to develop standard screening procedures to accelerate the testing/screening of compounds by the pharmaceutical industry.