As a child neurologist, I am often faced with a question raised by my patients and their families: why are there no medications to treat core symptoms of autism?
To be clear, the goal is for medications that could mitigate those symptoms that hamper the daily lives of some individuals with autism spectrum disorder (ASD), such as cognitive and language delays, social anxiety and isolation, and self-injury.
There have been , but they have fallen by the wayside. So the question might be better put this way: why do clinical trials of medications for autism repeatedly fail?
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Possible explanations are rooted in the design of trials, namely the way patients are chosen, the way outcomes are measured and how the placebo effect impacts them.
Autism can differ considerably from person to person, and those with the condition have a wide range of abilities and challenges, and there is no one cause. Yet clinical trials often, include all individuals, regardless of their particular pattern of symptoms. Because drugs are likely to be effective for certain subsets of people, we must find ways to select subgroups appropriately.
The placebo effect
When it comes to measuring outcomes, most trials rely on reports from parents and guardians or standardised assessments. These often cannot detect short-term change, which means that a child may actually make meaningful gains in certain areas, but that these gains may not be reflected in the standardised scores. What we need are measures that are sensitive to subtle changes that may even precede or predict changes in behaviour.
And, finally, we are hampered by the placebo effect. This describes the phenomenon by which patients in a trial’s control group – those who are not getting treatment or who are receiving a sugar pill – make considerable gains, sometimes as robust as the treatment group. A strong placebo response in a trial can spell the end for a new drug.
There are several reasons for this placebo effect in autism drug trials. First, taking part in a trial can be therapeutic for reasons other than the medication, such as raising parents’ awareness about their child’s development. Alternatively, strong belief in the potential of a drug could influence parents’ perception of child behaviour, leading to biased reporting of improvement. Repeated tests over the course of a trial can also lead to children becoming familiar with them and even learning some of the items on the test.
How do we overcome these issues? We need targeted, objective measures that can improve patient selection, predict or measure treatment response over a short time period, and that are resistant to placebo effects. Biomarkers, defined as objective measures of biological processes, can serve this purpose. We use biomarkers in other areas of medicine, such as blood glucose for diabetes or blood pressure for hypertension. In clinical trials for ASD, our search for biomarkers is not as simple as a blood test; we must focus on measures of brain function.
Collaborative effort
Studies have revealed that autism is not rooted in one part of the brain, but rather results from alterations in the way brain connections are formed over early development. These changes can influence a child’s attention to and learning from the environment, which then further impact brain function. We can measure these neurodevelopmental processes through tools such as electroencephalography (EEG), a non-invasive, painless method to record brain function in real-time. We can also examine and quantify an individual’s attention to information in the environment through eye-tracking technology.
Recently, the US National Institutes of Health funded the (ABC-CT), which is carrying out research that seeks to develop ASD biomarkers. Children with ASD aged 6 to 11 are tested on three separate occasions, with a comprehensive set of clinical assessments combined with rigorous EEG and eye tracking measures focused on baseline brain function and social information processing. The goal is to investigate and develop reliable biomarkers that may be used in clinical trials.
Last week at the annual meeting of the in the Netherlands, researchers from this project shared their interim data. The group has already found some promising EEG and eye tracking measures of social communication function that can be gathered robustly across a large age and cognitive range.
With collaborative efforts like this, substantial strides can be made towards the development of robust biomarkers to improve patient selection and to measure outcomes in ASD clinical trials. I am incredibly optimistic that progress will be rapid and that we are on the road to more effective interventions for autism.
Read more: Augmented reality glasses help kids with autism relate to others
