Current Pathophysiological and Therapeutic Options for Children with Hutchinson Gilford Syndrome

Abstract

Hutchinson-Gilford-Progeria syndrome (HGPS) cannot, to date, be treated causally. Therapy for affected children focus on alleviating the symptoms, treating secondary diseases and preventing complications such as strokes or heart attacks. Various medications and physiotherapeutic methods are primarily available for this extremely rare pediatric genetic disease. Lonafarnib, a farnesyltransferase inhibitor, has been used for the treatment of progeria in children since 2022, which can extend the life of children with HGPS up to 4 years. Farnesyltransferase inhibitors are able to block an enzyme that is involved in progerin processing. Progerin is the altered protein that occurs in HGPS due to the spelling mistake in the lamin A gene and accumulates within the cell nucleus envelope. As a result, the envelope is weakened and the cell nucleus becomes deformed. The spectrum of therapies includes progerin-targeting strategies on one hand and on therapies to alleviate the tremendous effects by progerin. Research focus on different new targets in the management of HGPS-like the farnesyltransferase inhibitor lonafarnib, Acetyltransferase NAT10-inhibitors, KAT 6a/b and -7 inhibitors, paclitaxel, small molecule ICMT-inhibitors, exportin CRM-1 Inhibitors, progerin-lamin A binding inhibitors (Progerinin), Ghrelin, micro-RNA inhibitors, doxycycline and the regulation of rapamycin complex 1 (mTORC1). This manuscript analyses these new therapeutic targets and pathophysiological aspects in a review manuscript.