Maria Eriksson

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare disorder, caused by a de novo point mutation in the LMNA gene, leading to mis-splicing and production of a truncated lamin A protein, named progerin. As progerin accumulates the disease progresses with devastating consequences on cells and tissues. Children show several typical symptoms of accelerated aging and die in their teens due to accelerated atherosclerosis and cardiovascular disease. Even though the underlying pathomechanisms for HGPS remain unclear, several treatment candidates have been tested in preclinical models but clinical trials have shown limited success. Even for a rare disease like HGPS there is a need to identify relevant disease mechanisms as they may be also shared with other more common diseases or aging. The discovery of non-coding RNAs (ncRNAs) as important regulators of both mRNA and protein expression, and their possible involvement in the different stages of atherosclerosis suggest that they could play important roles in the development of the early vascular aging seen in HGPS. We hypothesize that ncRNAs functionally contribute to the pathological HGPS hallmarks in the vascular wall and the development of cardiovascular disease. NcRNAs are thus far an underexplored aspect in the context of HGPS. We will try to identify ncRNA-linked HGPS disease pathways using scRNAseq, that might lead to more efficient therapeutic approaches based on ncRNA-neutralizing agents (including antisense oligos).