The Journal of Neurodevelopmental Disorders published four important articles this week which describe various steps in Fragile X research from gene discovery to potential treatment in Fragile X syndrome (FXS).
FXS is one of the most productive areas of research in neurodevelopmental disorders. Based upon results in mouse models, three pharmaceutical companies stepped up to test novel compounds in controlled trials in FXS. While early pilot studies proved hopeful, larger follow-up studies showed no significant findings in adults or adolescents with fragile X syndrome. As a result, one of the three companies folded and the other two pulled out of FXS research.
As Jeremy Veenstra-VanderWeele explains in his introductory article Translation in fragile X: no home runs in the first at-bat, researchers should not have expected to simply translate findings from a rodent model of FXS into humans. There have been successful translations in other fields (breast cancer, HIV), but, so far, there has not been a proven way to best test drugs for FXS. Veenstra-VanderWeele explains it this way: “To draw on a sports analogy, this would be like a professional golfer picking up a baseball bat and expecting to hit a home run on his first at-bat. The initial programs for these three compounds were three swings to hit the ball over the fence. None of the programs hit a home run. The good news is that baseball games are not determined by the first at-bat.”
The four articles offer perspectives on the challenges and potential rewards of the translational game. Click on each summary to read the full text.