Preclinical studies demonstrate potential of zelquistinel in autism


Robust efficacy in several preclinical models supports high translational potential of zelquistinel in autism and reflects broader opportunity across synaptic dysfunction disorders.

Gate Neurosciences has announced the publication of new peer-reviewed research demonstrating the therapeutic potential of zelquistinel (GATE-251) to address symptoms of autism spectrum disorder (ASD).

The paper, published in Neuropharmacology, showed the robust efficacy of zelquistinel in reducing social and behavioural symptoms of ASD in multiple mouse models, with the effects being more pronounced with longer treatment regimens at a lower dose level.

Zelquistinel, Gate Neurosciences’ lead programme, is a third-generation, rapid-acting oral drug candidate in its portfolio of NMDAR positive allosteric modulators (NMDAR PAMs), which are designed to enhance synaptic function in patients with mood and cognitive disorders.

Enhancing synaptic plasticity

Based on the role of disrupted synaptic plasticity and unbalanced excitation/inhibition in autism, scientists from Gate and the Université de Tours, France, sought to evaluate zelquistinel’s efficacy in addressing symptoms commonly associated with ASD.

The study was conducted in three different mouse models of ASD: two models of ASD caused by genetic factors, Shank3 mutant and Fmr1 null mice; and one model for ASD caused by environmental factors, mice exposed in utero to valproic acid. Zelquistinel was tested in 30, 100, 300, and 1,000μg/kg doses.

In genetic mouse models, a single dose of zelquistinel led to the resolution of behavioural symptoms, which was sustained for at least 24 hours. Administering a 100μg/kg dose of zelquistinel daily for 18 days fully resolved behavioural and social symptoms in nine days across all mouse models, and the effect was sustained for a longer period of time.

“It is now well-established that synaptic health and plasticity is closely tied to many diseases of the central nervous system,” said Mike McCully, CEO of Gate Neurosciences. “We believe that enhancing synaptic plasticity through NMDAR PAMs, such as zelquistinel, can rapidly and durably restore healthy brain function and relieve disease symptoms across mood, neuropsychiatric, neurodegenerative, and neurodevelopmental disorders like autism spectrum disorder. These are important findings for Gate, as we continue exploring our NMDAR PAM portfolio in diseases other than depression with synaptic dysfunction at their core.”

Read this DDW interview with Mike McCully.

Diana Spencer, Senior Digital Content Editor, DDW

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