Drug discovery: Testing a new approach to ADHD treatment

A phase I clinical trial to explore the safety of a new class of drug to treat attention-deficit hyperactivity disorder (ADHD) is published this week in Nature Communications. Most drugs used to treat ADHD are stimulants that act to raise dopamine levels. An alternative line of treatment, using a non-stimulant drug, shows some potential in this small study.

Human genetic studies have shown that mutations in genes related to the neurotransmitter metabotropic glutamate receptor (mGluR) signalling occur more frequently in some individuals with ADHD than in individuals without ADHD. Thus, Josephine Elia and colleagues sought to investigate the effects of a drug that targets the glutamatergic system to treat ADHD.

The authors tested fasoracetam monohydrate (NFC-1), an activator of mGluR system that had previously been explored as a possible treatment for dementia in adults, in a small group of adolescents with ADHD. The 30 participants (20 male and 10 female) were selected from an initial cohort of 200 based on the presence of mutations in mGluR signalling related genes. The authors show that during four weeks of an escalated dose treatment regimen there were few adverse effects, and these were mostly mild. The authors also reported that the drug treatment led to clinically detectable improvements, and one parent-reported measure of behavioural improvement. These improvements were strongest in those with mutations in genes most closely related to mGluR signalling.

This study demonstrates the safety of fasoracetam in adolescents with ADHD, and suggests that using genetic approaches to classify patients with mutations in mGluR may be useful in determining which patients are most likely to benefit from this treatment.