Testing medicines: GABA
Does the autistic brain respond differently to AZD7325, a medicine that targets the gamma-aminobutyric acid (GABA) system?
Researchers tested whether a medication currently called AZD7325 changed the function (or ‘shifted’) the Gamma-Aminobutyric acid (GABA) system differently in autistic people’s brains compared to non-autistic people’s brains.
GABA is a naturally occurring brain chemical, or neurotransmitter, that helps nerve cells communicate. It influences, among other things, how our brains deal with sensory information (such as sights, smells, tastes and touch), repetitive behaviour and sleep. Research has shown that there are differences in how the GABA system works in autistic and non-autistic people. Thus, two studies were conducted as it is important to understand prior to clinical trials whether medications that target the GABA system, such as AZD7325, act differently in an autistic person’s brain.
This video was created to introduce the concepts underlying the AIMS-2-TRIALS ‘Shiftability’ studies to those attending an internal consortium webinar at the end of June 2021.
The first study was a ‘shiftability’ study as it will check whether a single dose of the medicine ‘shifts’ brain activity; ‘shiftability’ studies are not clinical trials and aim to look at brain mechanisms only. A single dose of the medication or placebo was given to participants, on separate visit days, while they have an fMRI scan and EEG at ‘rest’ (i.e., without doing a task). They also completed tasks of impulsivity and sensory processing during the fMRI and EEG to see how their brain is working during these behaviours. Other sensory tests were conducted out of the scanner.
The responses of autistic and non-autistic adults after the drug and placebo were compared. One finding, for example, was that brain networks that are active during ‘rest’ communicated (or connected) differently after AZD7325 in autistic and non-autistic people. This distinct effect was strongest in sensory networks such as the visual network – which has lots of GABAA neurotransmitter signalling. Connectivity (or communication) within the visual network was increased in non-autistic people but decreased in autistic people. Thus, the GABAA system may function differently in autistic people and neurodivergence should be considered in current medical guidance as drugs that target the same GABAA neurotransmitter system are prescribed to autistic people for co-occurring anxiety for example. This distinct response should also be considered in future clinical trials of AZD7325.
Leaders of the Initial GABA Study (shiftability)
Lead organisation: King’s College London, with support from University of Coimbra as needed.
Principle Investigators: Prof Grainne McAlonan, Prof Declan Murphy and Prof Miguel Castelo-Branco
Research Centres: King’s College London with option of University of Coimbra
Leaders of the Second GABA Study (fast-fail)
Lead Organisation: King’s College London, University of Coimbra
Lead: Dr Eileen Daly
Principle Investigators: Dr Eileen Daly, Prof Declan Murphy, Prof Gráinne McAlonan, and Prof Miguel Castelo-Branco
Research Centres: King’s College London, University of Coimbra
