Drug Study Yields Double Effect: Preliminary Findings Show One Medicine Boosting Benefits in Fragile X Condition Twice Over
In a significant breakthrough, a team of researchers led by Lynne E. Maquat, Ph.D., the founding director of the Center for RNA Biology at the University of Rochester, have discovered the interaction between the enzyme AKT and the quality control pathway known as NMD in Fragile X Syndrome.
The study, published in the prestigious journal Molecular Cell, sheds light on the complex workings of these two critical components in the development of the neurological disorder. However, the search results do not provide specific information on who initially uncovered this interaction in the recent study, nor details about its implications for future therapies.
The research was funded by grants from the National Institutes of Health and a University of Rochester Provost's award. Apart from Maquat, Maximilian W. Popp, Christoph Pröschel, Joshua L. Schwartz, Gene W. Yeo, Hana Cho, Ph.D., and Elizabeth Abshire, Ph.D., co-lead study authors, also contributed to the study.
AKT, a hub for cell signaling, plays a key role in cell growth, survival, and protein production. Insulin stimulates AKT, and this study is the first to show that extracellular signaling changes the identity of the EJC (exon junction complex). The EJC promotes NMD when certain conditions are met, and AKT is a member of the complex of proteins that constitute the EJC.
NMD helps cells make smart decisions, supports gene expression, and aids in adjusting to changes in development and the environment. The team used neural stem cells that lack the FMRP protein in their study, as these cells mimic those affected by Fragile X Syndrome.
The team's findings provide good direction for future research on Fragile X Syndrome. They treated these cells with Afuresertib, a drug inhibiting AKT currently in phase 1 and 2 clinical trials for cancer. Blocking AKT in fragile X cells with Afuresertib decreased its activity and NMD as well, making the cells act more like typical, non-disease cells.
Moreover, the team developed a new tool for screening potential drugs that inhibit NMD. This tool could pave the way for the development of targeted therapies for Fragile X Syndrome and other diseases where NMD is hyperactivated, such as cancer.
The study in Molecular Cell reveals how AKT and NMD interact and provides a new mechanism by which AKT-signaling alters NMD and gene expression. This discovery offers hope for a better understanding and potential treatment of Fragile X Syndrome in the future.
