May 30, 2024
Keio University
Mie University
A research group led by Director/Professor Hideyuki Okano of the Keio University Regenerative Medicine Research Center (KRM) (at the time of research: Professor, Department of Physiology, Keio University School of Medicine), Project Assistant Professor Nicolas Leventoux of RIKEN (at the time of research: Project Assistant Professor, Department of Physiology, Keio University School of Medicine), Project Associate Professor Satoru Morimoto of the Keio Frontier Research & Education Collaborative Square (K-FRECS) [K-FRECS at Tonomachi] (at the time of research: Senior Assistant Professor, Department of Physiology, Keio University School of Medicine), and Visiting Professor Yasumasa Kokubo of the Graduate School of Regional Innovation Studies, Mie University, used iPS cell models derived from patients with amyotrophic lateral sclerosis/parkinsonism-dementia complex (Muro disease), which is prevalent on the Kii Peninsula. They generated astrocytes, which are thought to play a crucial role in the disease, and discovered a significant reduction in the gene and protein CHCHD2, which is important for mitochondrial function. Furthermore, they found that the neuroprotective function of these astrocytes was diminished, identified a method to restore this function, and confirmed that astrocytes in the brain and spinal cord of actual patients also exhibit CHCHD2 abnormalities.
For over 300 years since the name Muro disease was first recorded in literature, the cause of this disease has remained unknown. However, by using patient-derived iPS cell models and high-purity cell differentiation induction technology, the research group has now elucidated a key aspect of its pathology and successfully found a lead for iPS cell-based drug discovery.
This research elucidates the pathology of Muro disease, which had been shrouded in mystery with no existing disease models, and is expected to significantly accelerate the understanding of and drug discovery for this disease.
This research was published online on May 16, 2024, in the journal "Acta Neuropathologica," a prominent scientific journal on the pathology and etiology of neurological diseases.
Please see below for the full press release.