Cell therapy for Pompe disease using iPSC-derived muscle stem cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07067
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kyoto University
• Principal Investigator: Sakurai Hidetoshi 京都大学, iPS細胞研究所, 准教授 (80528745)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ポンペ病 / 細胞移植治療 / 遺伝子治療 / 酵素補充療法

Outline of Final Research Achievements

Pompe disease is a disease caused by mutations in GAA, resulting in abnormal accumulation of glycogen in lysosomes and damage to cardiac, liver, and skeletal muscles. Although enzyme replacement therapy has dramatically improved the prognosis of the patients, the improvement of skeletal muscle symptoms has been poor.
In this study, we applied gene therapy by over expressing GAA in iPS cells derived from Pompe disease patients, and then induced differentiation and transplantation of skeletal muscle stem cells from the cells to see if the over expressed GAA could be replenished at the same time as muscle regeneration and if it was effective as enzyme replacement therapy. The results showed that lysosomal hypertrophy disappeared not only in the grafted area but also in the surrounding muscle fibers. This suggests that the treatment was effective not only as a regenerative medicine but also as an enzyme replacement therapy.

Free Research Field

再生医学

Academic Significance and Societal Importance of the Research Achievements

ポンペ病はライソゾーム病に分類され、酵素補充療法によってその生命予後は劇的に改善した。しかしこの効果は心筋や肝臓での効果を反映しており、骨格筋に対する酵素補充の効果は限定的で、人工呼吸器の使用を余儀なくされる症例も多い。これは一つには骨格筋への酵素の取り込み効率が悪いこと、もう一つには骨格筋の体積が非常に大きく、十分な酵素の細胞内濃度を確保できないことにある。我々の開発した方法では、これらの問題点を解決しうることが示唆されており、今後のポンペ病に対して、自家iPS細胞への遺伝子治療を施した細胞移植酵素補充療法の確立に向けた第一歩になると期待される。