Synaptic synopsis

The early promise that neurotransmitter research would unlock the door for neurological diseases has devolved into sagging interest from several pharmas following repeated failures in clinical trials. Now, genetic findings are pointing to new targets in the synapse and reawakening commercial interest in fields such as autism spectrum disorders, schizophrenia and depression.

Although the behavioral features of those three conditions are quite dissimilar, new hypotheses about their origins suggest they all are diseases of connectivity. The common thread is synaptic dysfunction and disrupted communication between different brain regions.

The last decade has seen companies pursue compounds directed at new targets, in particular related to glutamate signaling because it contributes to the pathology of ASD, schizophrenia and depression.

In addition, data from recent academic-driven, large-scale genetic studies are pushing companies to pursue public-private partnerships (PPPs) as a way to explore new therapeutic real estate.

According to Atlas Venture partner Bruce Booth, academic research is injecting new life into the field.

"As industry has pulled back, academic research is advancing on the mechanistic basis of many of these diseases," he told SciBX.


There are more than 15 drugs approved for schizophrenia, at least 15 for depression and 2 for ASD. The majority are based on the early theory that the conditions are caused by an imbalance in monoamine neurotransmitters, most notably dopamine and serotonin.

The two ASD drugs, Risperdal risperidone and

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