Historically, drug discovery in disorders of brain development has been unproductive. This is largely due to the lack of a mechanistic understanding of these disorders as well as the absence of predictive animal models. As a result, while medications can be used to address individual symptoms such as anxiety and to manage problem behaviors such as irritability, therapeutics do not address the underlying neurobiology of these conditions.

Seaside Therapeutics is focusing on research to identify the fundamental pathophysiology of brain development disorders and applying that knowledge to develop targeted therapeutics. Seaside has its foundations in the breakthrough research of Mark Bear, PhD, a Howard Hughes Medical Institute Investigator and Professor of Neuroscience at M.I.T., who discovered that the mGluR5 signaling cascade is dysregulated in Fragile X Syndrome—the most common inherited form of mental retardation and the most common known cause of autism.  Bear and colleagues published in a 2007 issue of the journal Neuron results from a study demonstrating that knockdown of exaggerated mGluR5 signaling reverses most of the neuroanatomic and behavioral abnormalities that were examined in the Fragile X knockout mouse model.

With this in mind, Seaside licensed and is developing a novel series of compounds targeting the mGluR5 receptor—including lead compound STX107, a highly potent, selective mGluR5 antagonist in-licensed from Merck & Co., Inc. Seaside has demonstrated that STX107 reverses many of the behavioral abnormalities found in genetically engineered animal models of Fragile X. This research played a critical role in the selection of STX107 for continued development and provides a further link between Bear’s insight into the biology of Fragile X Syndrome and small molecule antagonists of the mGluR5 receptor.

The company initiated a Phase 1 single ascending dose study designed to evaluate the safety, tolerability, and pharmacokinetics of STX107 in healthy volunteers in November, 2009 and, with positive results, intends to begin studies of the drug candidate in individuals with Fragile X Syndrome in 2010. Seaside has been awarded translational research grants to support the development of STX107 from the National Institute of Mental Health, the National Institute of Child Health and Human Development, the National Institute of Neurological Disorders and Stroke, Autism Speaks, FRAXA, and the Best Pharmaceuticals for Children Act.