FRAXA and the Pierce Foundation are partners with Boston Children’s Hospital’s Fragile X Program and are pleased to help bring this important fragile X conference to the greater Boston community. Two FRAXA-supported researchers, Dr. Craig Erickson from Cincinnati Children’s Hospital and Dr. Carol Wilkinson from Boston Children’s Hospital will present their current work.
At FRAXA Research Foundation, we are truly grateful for our fragile X community and thousands of donors. We couldn’t keep moving the ball forward in research without your support. Each year FRAXA invests over $1 million in fragile X research thanks to your support. Because we supported these three researchers, we were able to secure another $35 million in research aimed at identifying clinical trial outcome measures that will lead to human trials of promising treatments for those affected by fragile X.
According to Dr. Erickson, AZD7325 is a drug that selectively boosts GABA neurotransmission in the brain. GABA is the primary neurochemical in the brain that blocks brain activation. GABA activity is in balance in the brain with Glutamate activity, which is the primary neurochemical that causes brain activation. In fragile X, GABA activity is insufficient and glutamate activity is excessive, likely causing brain activity to be out of balance. AZD7325 attempts to correct parts of this imbalance by boosting the insufficient GABA activity in the brains of people with fragile X
With a $51,000 grant from FRAXA Research Foundation, Dr. Craig Erickson will conduct a double-blind, placebo-controlled clinical trial of AZD7325 in adults with fragile X syndrome at Cincinnati Children’s Hospital. The compound being studied is an investigational new drug from AstraZeneca that targets GABA (A) receptors.
With a FRAXA Research Foundation grant of $30,000 in 2006, Dr. Erickson conducted a pilot clinical trial of an available medicine, aripiprazole (brand-name Abilify). This was an open-label 12-week trial in 12 people aged 6–25 years with fragile X. Results were promising, and published: 10 of the 12 participants showed behavioral improvements.
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.