New drug treatments in progeria cells: modulating mutated lamins to improve cell quality

Thirteen year study on lamin A and prelamin A biology have shown that the lamin A to prelamin A ratio is important to determine both physiological and pathological pathways. In the case of Hutchinson-Gilford Progeria, progerin amount relative to mature lamin A levels impacts on the cellular phenotype. Using a combination of retinoic acid and rapamycin, we could show that the lamin A to progerin ratio can be increased in progeria cells. This effect rescues the DNA repair machinery and the nuclear distribution of chromatin-associated proteins such as BAF and LAP2alpha. Most importantly, retinoic acid plus rapamycin treatment, performed using low doses of each drug, rescues cell cycle dynamics in laminopathic cells. These findings suggest that treating patients with progeria by retinoic acid- rapamycin combinations may reduce disease progression.