2-carba-cyclic phosphatidic acid derivative is a novel drug candidate for multiple sclerosis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K21229
• Project/Area Number (Other): 18H06111 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Saitama Medical University
• Principal Investigator: yamamoto shinji 埼玉医科大学, 保健医療学部, 助教 (70823318)
• Project Period (FY): 2018-08-24 – 2021-03-31
• Keywords: 多発性硬化症 / 脱髄 / クプリゾン / 2ccPA

Outline of Final Research Achievements

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, and axonal pathology. Cyclic phosphatidic acid (cPA) is a natural phospholipid mediator with a unique cyclic phosphate ring structure at the sn-2 and sn-3 positions of the glycerol backbone. We previously reported that the administration of cPA reduced cuprizone-induced demyelination. 2-Carba-cPA (2ccPA) is the compound in which one of the phosphate oxygen is replaced with a methylene group at the sn-2 position. In the present study, we investigated the effects of 2ccPA on the cuprizone-induced demyelination.
We demonstrated that 2ccPA protected oligodendrocytes via suppression of the mitochondrial apoptosis pathway. These data indicate that 2ccPA may be a promising compound for the development of new drugs to treat demyelinating disease and ameliorate the symptoms of MS.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

申請者が目指している2ccPAによるMS治療薬開発は、我が国の難病であるMSに苦しむ多くの患者のQOLの向上に資するものである。2ccPAはすでに、変形性関節症治療薬として米国FDA安全性試験をクリアし、化学合成法が確立されており、薬剤として十分な供給が可能である。また知的財産権の取得にも配慮しており、今後に向けて高い将来性を持つと考えている。