Abstract

Regenerative medicine is an important vanguard of the biomedical industries, and all countries urge to put in lots of resources in research and development. Taiwan Mitochondrion Applied Technology Co., Ltd (TaiMito) is an emerging leader in the worldwide development of regenerative medicine on mitochondrial technology. TaiMito focused on mitochondrial R&D and application technology platforms since 2014 and the first company that develops mitochondria as biologics through Mitochondrial Reconstruction Technology (MRT). The population of aging around world is increasing dramatically. Mitochondrial dysfunction is closely associated with the development of aging and degenerative diseases (such as Parkinson's disease and Alzheimer's disease... etc.). Because impaired mitochondria will be insufficient to energy supply and trigger reactive oxygen species induction, and even result in cells to enter apoptosis or autophagy, which will lead to disease. Currently, a number of product pipelines have been developing, including MitoCell (stem cells), MitoBio (Mitochondria), MAKcell (immune cells), MitoScan (functional mitochondria assay), and Stemoto (stem cell culturing medium). MitoCell, MitoBio, MAKCell are preparing to enter the next stage of clinical study, and other products or testing services are marketed in the fields of preventive healthcare supplements, aesthetic medicine, stem cell culture medium, health examination, and mitochondrial metabolomics. These products or services have been demonstrated to be safe, and effective in preliminary studies. Our major priority is to launch the MitoCell to targeted markets. MitoCell is an autologous stem cell product that cultures with the company's unique patented medium. The mechanism of action (MOA) of MitoCell is to improve the brain microenvironment in neurodegenerative disease. MitoCell which like mesenchymal stem cells can modulate the immune response. Moreover, MitoCell can secrete more abundant regulators, such as BDNF/GDNF, SDF-1, IL-1ra, BECN-1...etc., to help dopamine neurons (DA) repair, restore, and regenerate, and even eliminate toxic α-Synuclein through up-regulating autophagy. Therefore, MitoCell can reconstruct the brain environment to a better site for DA residents and showed more efficacy than other stem cells. In our study, BDNF is one of the major potency markers of MitoCell. We have successfully initiated MitoCell to phase I open-label dose-escalation study to evaluate the safety, tolerability, and efficacy of autologous MitoCell intracranial transplantation in subjects with idiopathic Parkinson’s disease which rating from stage 3 ~ 4 of modified Hoehn & Yahr staging. Two dose levels will be tested. This clinical trial plans to enroll approximately 4 subjects to obtain 3 evaluable subjects successfully receiving 3×107 cells/hemisphere (total 6×107 cells, Cohort 1) and approximately 8 subjects to obtain 6 evaluable subjects for 1×108 cells/hemisphere (total 2×108 cells, Cohort 2). The primary objective of this study is to assess the safety profile of autologous MitoCell administered to PD patients, and secondary objective is to explore the efficacy and safety of MitoCell given as the recommended dose by stereotactic intrastriatal implantation.