Targeting Mitochondria in Human Fragile X Syndrome Neurons
Principal Investigator
FRAXA Postdoctoral Fellow
Madison, WI
Summary
FRAXA Research Foundation has awarded a $90,000 research grant to principal investigator Dr. Xinyu Zhao and postdoctoral fellow Dr. Minjie Shen at the University of Wisconsin.
They are investigating whether drugs which boost mitochondria — which provide the energy for cells — could treat Fragile X syndrome.
The Results
After conducting this research, Dr. Zhao and her colleagues determined that the pattern of smaller mitochondria in Fragile X patients was also exhibited in humans. However, not only were the mitochondria smaller, there were also fewer of them. This highlighted that humans with Fragile-X syndrome are even more affected than the mice models. The deficiency of FMRP protein in Fragile-X patients affects the mitochondria production as well as messenger RNA.
This research expanded information on the molecular, and prenatal, development of FXS before an individual starts exhibiting symptoms. New treatments can now be targeted during development. Zhao’s research also discovered that the addition of the insufficient gene RACK1 helped increase and strengthen the fewer and smaller mitochondria seen in FXS individuals. Using MEA, a microelectrode array, technology allowed for Zhao to screen for these treatments.
The Science
Mitochondria are powerhouses that generates energy inside each cell. Neurons need a lot of energy during their development as well as when they perform daily functions. Work from the Dr. Xinyu Zhao’s lab and many other labs has shown that neurons in Fragile X mice do not develop normally. However the reasons are not fully clear.
Recently, Dr. Minjie Shen in Dr. Zhao’s lab found that mouse Fragile X neurons have smaller mitochondria which do not work as well as they should. When they treated Fragile X mice with mitochondria-enhancing compounds, they were able to correct some of the behavioral deficits seen in these mice and also in Fragile X patients. These data suggest that mitochondria might be a potential new treatment target for Fragile X syndrome.
The team believes that the next key step is to extend these findings to humans. In this project, Dr. Shen will determine whether human Fragile X neurons exhibit mitochondrial impairment and whether mitochondria-enhancing compounds can correct neuronal development deficits of these neurons. This project will be carried out under the guidance of Dr. Xinyu Zhao and in collaboration with Dr. Anita Bhattacharyya and Dr. Shaoqin Gong, all at the University of Wisconsin-Madison.
