Safety and efficacy of mesenchymal stem cell therapy for Hutchinson-Gilford Progeria syndrome

초록

Introduction) Hutchinson?Gilford progeria syndrome (HGPS; MIM # 176670) is an extremely rare genetic disorder, characterized by rapidly accelerating aging and severe health issues like rapidly progressive atherosclerosis issues, resulting in an average lifespan of 14.5 years. The classic form is caused by a mutation in LMNA gene on Chromosome 1q22 (c.1824C > T, p.G608G), leading to the production of a defective protein called progerin, which disrupts nuclear stability, cellular function and stem cell driven regeneration. Mesenchymal stem cells (MSCs) modulate the immune response and effectiveness in treating autoimmune and chronic inflammatory diseases, as well as reducing blood lipid levels to potentially slow atherosclerosis. This clinical trial aimed to slow the progression of progeria and extend lifespan using MSCs therapy. This clinical trial aimed to slow the progression of progeria and extend lifespan through MSC therapy. methods) This clinical trial, approved as a high-risk cell therapy research project by the Advanced Regenerative Medicine Clinical Research Support Project (R-3-0005, IUH IRB 2023-04-038), was conducted from September 2023 to July 2024. The participiant was scheduled to receive MSCs therapy five times over two years, with interim evaluations and follow-up assessments to monitor the outcomes. Result) No significant adverse effects closely related to the administration. Improvement of bone density, reductions in inflammatory markers and improvement of dental crowding were observed, whereas structural changes were not alleviated and continued to show slow progressive cardiovascular deteriorations. Discussion) To accurately evaluate efficacy of MSC treatment, it is necessary to consider alterations in dosage and administration schedule. Also, long-term monitoring required to fully assess the sustained effects and potential risks associated with the stem cell therapy.