The rarest of the rare – exploring non-coding RNA in the disease pathogenesis of Hutchinson-Gilford progeria syndrome
Cell Biology
Final Report Abstract
Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic condition caused by a mutation in the LMNA gene, which results in the production of a defective prelamin A protein called progerin. This leads to symptoms resembling accelerated aging, with affected children typically succumbing to cardiovascular complications in their teens. Despite extensive research, the underlying mechanisms remain poorly understood, and current treatments offer limited efficacy. Our project focuses on the underexamined role of non-coding RNAs (ncRNAs) in driving HGPS-related abnormalities. These ncRNAs, which regulating key processes like abnormal RNA splicing, DNA damage responses, senescence, and fibrotic signaling may be causally linked hallmarks of HGPS. Using cutting-edge single-cell sequencing technologies, we aim to identify disease-relevant ncRNAs in experimental models, including patient-derived cells and HGPS mouse models. Promising ncRNAs will be tested for their therapeutic potential using oligonucleotide-based treatments, such as antisense oligos and antagomiRs, in preclinical models. This interdisciplinary project, involving experts from Sweden, Italy, Austria, and Germany, in collaboration with the Progeria Research Foundation, seeks to uncover ncRNA-linked pathways and develop innovative therapies, offering new hope for HGPS patients and their families.
