Abstract
BACKGROUND/OBJECTIVES: Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that cause premature aging due to LMNA mutations and progerin accumulation. Although lonafarnib, an FDA-approved farnesyltransferase inhibitor, offers modest extension of life, the disease remains progressive. 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 and preexisting severe cerebrovascular disease received four intravenous infusion of bone marrow-derived MSCs (2.5 × 10⁵ cells/kg) over 8 months. Growth, metabolic, cardiovascular, musculoskeletal, auditory, and inflammatory cytokines were monitored throughout the study. Prophylactic enoxaparin was administered to prevent vascular complications. RESULTS: MSC therapy was associated with improved lean body mass (11.5%), bone mineral density (L-spine z-score: 0.55 → 2.03), reduced arterial stiffness (9.98% reductionin pulse wave velocity), joint range of motion, dentition, and decreased sICAM-1 levels. However, Cardiovascular deterioration continued, and the patient passed away 10 months after the fourth dose, likely due to progression of the underlying vascular disease. No severe adverse effects were attributed to MSC therapy. CONCLUSIONS: MSC therapy may offer short-term benefits in arterial stiffness, bone health and inflammation in HGPS without notable safety concerns. Further studies are warranted to validate these findings, explore earlier intervention, and determine long-term efficacy and optimal dosing strategies.