With a $90,000 grant from FRAXA Research Foundation over 2017-2018, Dr. Frank Kooy at the University of Antwerp, Belgium, is investigating whether phosphorylation abnormalities are a suitable biomarker for the Fragile X syndrome.
Drs. Anke Van Dijck (FRAXA fellow, ganaxolone clinical trial), Ilse van der Werf, Geert Vandeweyer, Elisa Cappuyns (FRAXA fellow, this study), Frank Kooy
“This Is Your Brain on Drugs” was a large-scale US anti-drugs TV campaign promoted by Partnership for a Drug-Free America in 1987. The purpose was to discourage use of illegal drugs by showing an egg frying in a pan simulating what drugs can due to your brain. It was incredibly simple and effective. TV Guide named it one of the top 100 commercials of all time.
University of Antwerp researcher Frank Kooy, PhD, has a completely different update on the TV commercial. He wants to show the opposite effect of what an effective drug he is researching can do to the Fragile X brain. He is working on Fragile X mice that show the same abnormalities that stimulate the inhibitory system in the brain of humans with Fragile X. In other words, if successful, his new drug will lead to human trials where those with Fragile X could become less excitable.
About time, right?
Excitation and Inhibition
“Our brain is composed of excitatory and inhibitory cells called neurons,” Kooy said. “These neurons communicate with each other and there is overwhelming evidence the balance between inhibition and excitation is disturbed in the Fragile X syndrome.”
Kooy’s goal is to use effective drugs that interfere with the inhibitory system to improve some of the clinical symptoms in patients.
“We are optimistic drugs that enhance the GABAergic system, which plays the principal role in reducing neuronal excitability throughout the nervous system, can be used for clinical trials,” he said.
Kooy initiated his current project because of previously funded FRAXA work in clinical trials. The journey will not be easy. Previous research led to the identification of a novel pathway involved in Fragile X (GABA). While it is possible to interfere with this pathway using drugs already in development, many drugs in many different dosages will need to be tested to find out the most suitable for treatment. This requires a long-term commitment from a small group of dedicated investigators.
Outcome Measures are Key
“When we participated in one such trial, we found out there is a lack of easy to measure outcome measures,” he said. “We noticed there are various reports of the activity of several proteins in patients that are altered. With this project, we aim to measure the activity of all of these proteins in a single and simple assay. The aim is to develop a simple outcome measure that can be used in future clinical trials.”
Kooy credits FRAXA for funding most of his research.
“FRAXA has been my most important funding support,” said Kooy, who has received more than $300,000 in FRAXA funding since 1999. “FRAXA was the first foundation to grant my work. With the aid of that grant, I was able to generate sufficient preliminary data to obtain grants from our national founding organizations. The current grant is extremely helpful and will enable me to invest more in biomarker development. Because FRAXA knows the field so well, they are very capable of selecting the most relevant and timely topics for research.
“My professional life is dominated by Fragile X. Although we work on other forms of autism and intellectual disability, much of the attention goes to Fragile X as a prime example for the development of targeted treatment for other disorders. Many of my professional contacts come from the Fragile X field and I treasure each one of those.”