Since the advent of induced pluripotent stem cell (iPSC) technology 18 years ago, significant progress has been made in stem cell medicine. Human iPSC-derived neural cells, the utility of which has been somewhat elusive, are now expected to be applied in many fields. As the pathophysiology of various diseases is being clarified, new drugs derived from the screening of iPSCs are also being developed. In parallel with this, recent advances in new technologies are providing opportunities to appreciate iPSC-based platforms more than ever in the challenge of translational research in neurodegenerative diseases.

We conducted disease modeling, drug screening, patient stratification, in vitro trials, drug discoveries, physician-initiated clinical trials, AI diagnosis support, or data-driven genomics by using this unprecedented resource.

In this lecture, I would like to talk about our recent efforts and discuss various perspectives of both basic and clinical research for neurodegenerative diseases by using iPSC technology.

References:

1. Repurposing bromocriptine for Aβ metabolism in Alzheimer’s disease (REBRAnD) study: randomised placebo-controlled double-blind comparative trial and open-label extension trial to investigate the safety and efficacy of bromocriptine in Alzheimer’s disease with presenilin 1 (PSEN1) mutations. BMJ Open 11(6): e051343, 2021

2. Dissection of the polygenic architecture of neuronal Aβ production using a large sample of individual iPSC lines derived from Alzheimer’s disease patients. Nature Aging 2: 125–139, 2022

3. Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial. eClinical Medicine 53,101707, 2022

4. TDP-43 regulates cholesterol biosynthesis by inhibiting sterol regulatory element-binding protein 2. Scientific Reports 12(1):7988, 2022