Development of a novel therapeutics targeting amylin oligomers for diabetes mellitus

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19522
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Oita University
• Principal Investigator: Matsubara Etsuro 大分大学, 医学部, 教授 (70219468)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: 糖尿病 / アミリン / オリゴマー / コンフォメーション病

Outline of Final Research Achievements

Islet amyloid polypeptide (amylin) plays a central role in type 2 diabetes (T2D) pathogenesis, and is implicated in a degeneration or death of pancreatic β cells, which share a common molecular basis of a synaptic failure with Alzheimer’s disease. We investigated the pathological relevance of the “amylin oligomer cascade hypothesis” in T2D by means of conformational anti-Aβ oligomer antibody. Dot-immunoblot analysis employing 72D9-6H4 revealed its immunoreactivity with amylin oligomers alone. The Live/Dead assay using trypan-blue of pancreatic pancreatic β cells after 24-h-exposure to amylin oligomers and Aβ oligomers revealed significant neuronal death, whereas the 72D-6H4 antibody nearly completely blocked both toxicity, indicating that T2D and Alzheimer’s disease represents conformational disorder, in which we can share the conformational antibody as a disease modifying candidate.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、アルツハイマー病と糖尿病発症の鍵となるオリゴマー分子に共通して存在する立体構造異常を認識する申請者のみが所有する独創的ツールを用いて、これまで糖尿病研究領域では何故か浸透せず、その整合性が未検証であった“2型糖尿病がADと共通の発症基盤を有する「コンフォメーション病」であることを検証する中で、糖尿病の根本的治療薬の開発を目指した研究である。