With a $100,000 grant from the FRAXA Research Foundation in 2015, Dr. Peter Vanderklish explored a novel strategy to treat fragile X syndrome: AMPK activators. The good news is that there are FDA approved (for example, metformin) and naturally occurring AMPK activators (such as resveratrol, found in red wine).
With a $124,000 grant from the FRAXA Research Foundation from 2012-2014, Dr. Mara Dierssen and Dr. Rafael de la Torre conducted preclinical studies in fragile X knockout mice and a clinical trial in fragile X patients using Mega Green Tea Extract, which contains 45% by weight epigallocatechin gallate (EGCG).
With a $180,000 grant from the FRAXA Research Foundation over 2011-2014, Dr. Yue Feng and Dr. Wenqi Li at Emory University will study CDK5 pathway function and regulation in an effort to break down whether and how CDK5 signaling is affected by the loss of the fragile X protein, FMRP, in the fragile X mouse model.
Of the many genes known to be regulated by FMRP, the gamma-aminobutyric acid receptor A (GABA(A)), is gaining attention as a potential target for the treatment of FXS. Mounting evidence suggests decreased expression and functioning of GABA(A) is involved in the pathophysiology of FXS. Non-selective GABA(A) agonism in animal models of FXS has been associated with normalization of morphological features, GABA(A) expression, and behavior. However, the clinical use of these agents in fragile X is associated with unwanted side-effects, such as sedation, dulling of cognition, and occasional paradoxical agitation, which limits their use. Given the limitations in available GABA(A)-based treatment of FXS, this group plans to investigate a novel selective GABA(A) agonist in a mouse model of FXS. This agent has the potential to relieve many symptoms of fragile X without the unwanted side effects.
With a $90,000 grant from FRAXA Research Foundation over two years, Drs. Olivier Manzoni and Daniela Neuhofer researched the relationship between fragile X syndrome and the areas of the brain that are involved in reward processing, regulation of emotional behavior and emotional memory as well as attention, planning and working memory.
With a $120,000 grant from FRAXA Research Foundation during 2011-2012, Dr. Cara Westmark at the University of Wisconsin explored the role of AbPP as a potential treatment option for fragile X. AbPP produces b-amyloid which is over-expressed in Alzheimer’s disease (AD) and Down syndrome.
Dr. Davidovic has been examining changes in metabolism in various brain regions that are affected in fragile X patients. She has defined a brain-specific metabolic signature of FXS and is testing treatment strategies to restore normal levels of these metabolites.