July 2, 2019
Tohoku University Graduate School of Medicine
Tohoku Medical Megabank Organization, Tohoku University
Tohoku University Hospital
Keio University School of Medicine
Japan Agency for Medical Research and Development
A research group led by Assistant Professor Tetsuya Akiyama of the Tohoku Medical Megabank Organization, Tohoku University; Assistant Professor Naoki Suzuki, In-hospital Lecturer Hitoshi Warita, and Professor Masashi Aoki of the Department of Neurology, Tohoku University Graduate School of Medicine; and Professor Hideyuki Okano of the Department of Physiology, Keio University School of Medicine, has discovered a new pathology in ALS motor neurons using iPS cells derived from ALS patients.
ALS, a designated intractable disease in Japan, is a neurodegenerative disorder affecting motor neurons throughout the body, leading to the progressive weakening of muscles in the limbs and those required for breathing. In severe cases, patients may require a wheelchair or an artificial respirator. It is known that in the motor neurons of ALS patients, the projection structures called "axons," which extend from the neuron's cell body to the muscles, are damaged at an early stage. In this study, the research group generated motor neurons from iPS cells with a mutation in the FUS gene, one of the causes of ALS, and discovered that the axons of these motor neurons exhibited an abnormal morphology. Furthermore, by combining a novel microfluidic device with RNA sequencing, they found that the Fos-B gene plays a central role in the abnormal axonal morphology of motor neurons. Since the abnormal axonal morphology occurs before the neurodegeneration seen in ALS, Fos-B is expected to be a potential early therapeutic target.
The results of this research were published in the open-access academic journal "EBioMedicine" on June 29, 2019 (JST). This research was supported by the Japan Agency for Medical Research and Development (AMED) and other funding.
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