Smith-Magenis Syndrome (SMS) is a rare neurodevelopmental disorder that results from a missing piece of genetic material on the 17th chromosome. This deleted portion includes the Rai1 gene, which causes many of the features we commonly see in SMS, including intellectual disability, early onset obesity, an inverted sleep cycle, self-injurious behaviors, and craniofacial anomalies, among other concerns. Approximately 10% of SMS diagnoses are due to a mutation that occurs within the Rai1 gene

The SMS Research Foundation is a 501(c)(3) nonprofit organization founded in June 2010 by SMS parents, Missy Longman and Jennifer Iannuzzi, who saw a significant gap in professional awareness, treatment knowledge, and research funding for SMS. The mission of the Foundation is to fund research leading to innovative treatment options for those living with SMS. Your support helps us move one step closer to finding answers to this complex disorder and create a brighter future for SMS individuals and their families.

Current Research Projects 

Researchers at Baylor College of Medicine are completing the proof of concept phase on the gene therapy project. The goal of the project is to normalize the function of Rai1. One approach they are taking is to bring the amount of Rai1 up to normal levels by inserting the gene into specific cells/tissues that are important for the problems we observe in SMS. Another approach is to increase the expression of Rai1 by amplifying the production from the one good copy of the gene using cas-9 CRISPR technology. This proof of concept will allow us to determine if normalizing the function of Rai1 can positively impact cognition, obesity, sleep, and behavioral concerns in SMS and help us refine the treatment approach to achieve the best outcomes for therapy.  

At the SMS Lab at McGill University, researchers are leveraging molecular screening tools to identify key targets that alter Rai1 protein levels. By identifying these targets, researchers can then begin to develop drugs against these targets, with the goal of improving SMS symptoms.

At the Kavli Institute for Neuroscience at Yale University, researchers are studying how the disruption of Rai1 alters the development and function of the brain. A major hypothesis across many neurodevelopmental disorders is that the coordination of activity between different brain areas is disrupted, negatively affecting cognitive and emotional abilities. By imaging neocortical signals in mice lacking the Rai1 gene, they hope to identify previously unknown functional signatures of brain activity associated with SMS. They also hope to generate a novel experimental platform from which to evaluate potential therapies aimed at modifying brain activity and improving functional outcomes for SMS patients.