Improved Arterial Stiffness and Bone Mineral Density in Hutchinson–Gilford Progeria Treated with Bone Marrow-Derived Mesenchymal Stem Cells: A Case Study and Literature Review

Background/Objectives: Hutchinson‒Gilford progeria syndrome (HGPS) is a rare ge-netic disorder caused by LMNA gene mutations, leading to the accumulation of farne-sylated progerin. It is characterized by severe growth failure, premature aging, rapid progression of atherosclerosis and cardiovascular- related early disease. Lonafarnib, a farnesyltransferase inhibitor, extends life expectancy in HGPS, but it does not stop progression. As Progeria is associated with stem cell depletion and mesenchymal stem cell (MSC) therapy has shown efficacy in treating atherosclerosis, we aimed to evaluate its efficacy and safety in HGPS. Methods: A 7-year-old male with classic HGPS re-ceived intravenous bone marrow-derived MSCs (2.5x10⁵ cells/kg) over four sessions. The first three sessions were administered at one-month intervals, followed by a final session six months later (Months 0, 1, 2, and 8). The study protocol included compre-hensive baseline assessment (growth, metabolic, cardiovascular, musculoskeletal, au-ditory and proinflammatory markers including cytokines). Preventive enoxaparin was administered to mitigate vascular complications. Results: MSC therapy increased lean body mass (total: pre -0.8% vs. post 11.5%), improved BMD (TBLH: pre -20.5% vs. post +2.8%, lumbar: pre +0.6% vs. post +26.5%), decreased PWV by a mean of 9.98%, and promoted weight gain (z score change: pre -1.13 to post + 0.75). Additionally, it en-hanced ROM, improved the low frequency of hearing loss, and consistently reduced sICAM-1. Conclusions: MSC therapy demonstrated potential efficacy in improving clinical outcomes, including arterial stiffness and bone mineral density, with no severe safety concerns related to therapy. Further research is needed for long-term efficacy and to maximize benefits.