Poster abstracts
Poster number 54 submitted by Taylor Feldt
A novel RNA based gene therapy approach to modulate gene expression for treatment of severe neurological disorders caused by mutations in FOXG1
Taylor Feldt (MCDB)
Abstract:
FOXG1 syndrome is a newly classified syndrome that causes developmental delays and structural abnormalities in the brain due to de-novo heterozygous mutations in the FOXG1 gene. FOXG1 syndrome was previously thought to be a congenital form of Rett’s syndrome and has since been reclassified as a new syndrome with its own unique phenotype. Unlike Rett’s syndrome, children affected by mutations in this gene never achieve developmental milestones, and instead have developmental delays and abnormalities that begin in utero. This is likely due to the crucial role the FOXG1 gene plays in development of the telencephalon. The FOXG1 gene is highly conserved and plays a non-redundant role in neural development and is reused at different times in different locations in the developing brain. As a newly classified syndrome, not much is known about the role the FOXG1 gene plays in disease pathology however, current research has discovered mutations in FOXG1 are typically unique to each patient. FOXG1 syndrome has proven to be an intellectually puzzling syndrome that could lead to innovative solutions and new treatments. The goal of this project is to better classify the FOXG1 gene itself, including promoter regions and the impact of mutations within different functional domains. The lab aims to achieve this through bioinformatics techniques as well as the development of an in-vitro model system for the syndrome using patient derived fibroblasts. This will allow us to determine the unique effects of mutations within certain defined functional domains of the FOXG1 gene. Further, the use of a FOXG1 in-vitro model will be crucial in the testing of established small drug molecules as potential new therapeutics to better fit the needs of patients.
References:
Akol I, Gather F, Vogel T. Paving Therapeutic Avenues for FOXG1 Syndrome: Untangling Genotypes and Phenotypes from a Molecular Perspective. International Journal of Molecular Sciences. 2022; 23(2):954.
Dastidar, S. G., Landrieu, P. M., & D'Mello, S. R. (2011). FoxG1 promotes the survival of postmitotic neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience, 31(2), 402–413.
Mitter, D., Pringsheim, M., Kaulisch, M. et al. FOXG1 syndrome: genotype–phenotype association in 83 patients with FOXG1 variants. Genet Med 20, 98–108 (2018).
Murphy et al., 1994; Li et al., 1995; Bourguignon et al., 1998 – FOXG1 structure & function
Ni Y, Liu B, Wu X, Liu J, Ba R, Zhao C. FOXG1 Directly Suppresses Wnt5a During the Development of the Hippocampus. Neurosci Bull. 2021 Mar;37(3):298-310.
Keywords: FOXG1 , Gene Therapy , RNA Reprogramming