Christie Lab receives $50,000 grant to study potential Fragile X Syndrome therapy

A hormone released from fat cells could help alleviate the symptoms of Fragile X Syndrome (FXS), the most common form of genetically inherited intellectual disability and a leading cause of autism.

The potential therapy is the focus of a new study by Drs. Jonathan Thacker and Luis Bettio, postdoctoral fellows in the Christie Lab at the University of Victoria’s Division of Medical Science. Dr. Brian Christie received a $50,000 research grant jointly awarded by FRAXA Research Foundation in the U.S. and the Fragile X Research Foundation of Canada.

“We have preliminary data that indicates adiponectin, a hormone released from fat cells—or, adipocytes—can enhance cognitive function,” says Christie. “This work was initiated by a previous postdoctoral fellow, Dr. Sonata Yau, who now has her own laboratory in Hong Kong.”

FXS is a neurological condition caused by a mutation of the Fmr1 gene, and results in the loss of fragile X mental retardation protein (FMRP). Patients with FXS usually present deficits in cognition, language, sensory integration, and emotional responses as FMRP controls the translation of several proteins critical for synaptic function, explains Bettio.

“FXS is unique in that the native mutation to the FMRP gene drastically increases protein synthesis and favors increased synapse density, which impairs learning and memory,” says Thacker. “Our research approach is unique as we are attempting to reintroduce the ‘brakes’ on protein synthesis, which in theory should reduce synapse numbers to normal levels and restore learning and memory.”

The team hypothesises they can improve cognitive and emotional responses by boosting levels of adiponectin, which patients with FXS do not readily produce. 

“[Adiponectin] regulates a number of proteins, notably mTOR. mTOR is one of the critical regulatory proteins involved in protein synthesis and in the absence of FMRP, mTOR activity is drastically increased. Thus, by reducing mTOR activity with adiponectin, we are able to reduce protein synthesis, which we have also shown improves cellular correlates of learning and memory,” says Thacker.

This research builds on a previous FXS break through at the Christie Lab that found FXS involves changes at the level of a subclass of glutamate receptors known as N-methyl-D-aspartate (NMDA) receptors; receptors known to be both sufficient and necessary for learning. Adiponectin has been shown to facilitate the same molecular pathways that NMDA receptors are involved in.

If the hypothesis proves true, the research results could lead to the novel use of dietary adiponectin supplements to treat FXS symptoms.

“Adiponectin levels can be manipulated in vivo in response to a number of behavioral interventions such as fasting, which can be quickly implemented at low cost,” says Thacker. “This research has the potential to drastically improve the quality of life of those individuals with FXS.”