Assessing BKCa channel openers for the treatment of sensory hypersensitivity in ASD

  • Awarded: 2017
  • Award Type: Pilot
  • Award #: 402454

Defects in sensory information processing are considered to be almost universal in individuals with autism spectrum disorder (ASD). In addition, alterations in sensory responsiveness have been strongly suggested to co-segregate with other ASD-related phenotypes. Such response alterations may even be determinant of certain behaviors, such as behavioral disturbances that manifest as a result of the individual’s inability to respond appropriately to painful or overstimulating environments.

Sensory information is processed and integrated in the neocortex, making this brain area eminently suited to the evaluation of sensory-evoked information. Andreas Frick and colleagues recently provided a link between dysfunction of large-conductance calcium- and voltage-activated K+ (BKCa) channel, neocortical hyperexcitability, sensory hypersensitivity as well as other phenotypes in the Fmr1–/y mouse model of ASD1,2. These findings suggest that BKCa channels might be targeted for therapeutic rescues of symptoms associated with neuronal hyperexcitability/sensory hypersensitivity in ASD. In spite of the promise of these findings, a number of important challenges remain.

To address these challenges, Frick’s team proposes to identify and further characterize experimental models for sensory hypersensitivity and neocortical hyperexcitability by examining neocortical responses to sensory stimuli across a range of modalities. Frick will identify a neuronal signature for these models to enable further testing, in in vitro assays, the action of novel BKCa channel agonists on neocortical function. Finally, the group will develop approaches to test these novel compounds in in vivo assays. Ultimately, this work will help to develop a platform for understanding changes in sensory information processing in the neocortex in rodent models of ASD, in addition to furthering the development of novel therapeutic approaches for treating this disorder.



1.Zhang Y., et al. Nat. Neurosci. 17, 1701-1709 (2014) PubMed
2.Carreno-Munoz M.I., et al. Neuropsychopharm. Epub ahead of print (2017) PubMed
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