A research group has made significant strides in understanding Muro disease―a prevalent condition in the Kii Peninsula of Japan that manifests as an amyotrophic lateral sclerosis (ALS) and Parkinson's disease dementia complex. The group included Professor Hideyuki Okano (currently director of the Keio University Regenerative Medicine Research Center) and Project Assistant Professor Nicolas Leventoux (currently a research scientist at RIKEN) from the Department of Physiology at the Keio University School of Medicine, Assistant Professor Satoshi Morimoto (currently project associate professor at the Keio University Frontier Research & Education Collaborative Square [K-FRECS]), Guest Professor Yasumasa Kokubo from the Mie University Graduate School of Regional Innovation Studies, and colleagues. By using induced pluripotent stem cell (iPS cell) models derived from Muro disease patients, the team successfully created astrocytes―cells believed to play a crucial role in the disease―and revealed a significant decrease in the expression of CHCHD2, a gene and protein critical for mitochondrial function. Further, they identified a decline in the neuroprotective functions of these astrocytes, developed methods to restore these functions, and confirmed abnormalities in CHCHD2 in astrocytes within the brains and spinal cords of actual patients.
For over 300 years since Muro disease was first documented, its cause has remained unknown. In a major step forward, researchers have employed patient-derived iPS cell models and advanced cell differentiation techniques to elucidate critical aspects of the disease's pathology, paving the way for iPS cell-based drug discovery.
This breakthrough sheds light on the previously enigmatic Muro disease―an illness for which no animal disease models even existed―significantly advancing our understanding and opening new avenues for developing treatment.
These research findings were published online on May 16, 2024, in the renowned scientific journal Acta Neuropathologica, which focuses on the pathology and etiology of neurological disorders.
