News Releases & Research Results Novel drug candidate for polyglutamine (polyQ) diseases, intractable neurodegenerative diseases – Protein structure-stabilizing effects of L-arginine against aggregation

The results of collaborative research conducted by Professor of Endowed Chair Yoshitaka Nagai of Osaka University Graduate School of Medicine, Professor of the Department of Neurology and Director of the Brain Research Institute Osamu Onodera of Niigata University, Director Keiji Wada (currently adviser), Researcher of the 4th Department Eiko Minakawa, Researcher Helena Akiko Popiel (currently Tokyo Medical University) of the National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), and others.

• Amino acid L-arginine was identified as a candidate drug for the treatment of polyglutamine (polyQ) diseases (*), intractable neurodegenerative diseases.
  *Intractable diseases in which structurally unstable mutant proteins due to abnormally expanded polyQ stretches aggregate and accumulate as inclusion bodies in the nerve cells of the brain and spinal cord, resulting in neuronal death. Several compounds that suppress the aggregation of abnormally expanded polyQ proteins have been identified, but it could not be clinically applied as therapeutic drugs because of their low safety to the human body and inefficient incorporation into the brain.
• An experiment with a polyQ disease animal model demonstrated that L-arginine improved motor symptoms and pathological brain findings when orally administered.
• An investigator-initiated clinical trialis being planned on spinocerebellar ataxia type 6, the most common polyQ disease in Japan.

This research project was conducted with the support of the Project of Translational and Clinical Research Core Centers and the Practical Research Project for Rare/Intractable Diseases by AMED.

The results of research were published in the British scientific journal Brain on May 22.

Eiko N. Minakawa, et al. Arginine is a disease modifier for polyQ disease models that stabilizes polyQ protein conformation Brain
DOI：10.1093/brain/awaa115