Development of prevention of Alzheimer's disease using transgenic soybean expressing amyloid beta protein

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07989
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Gunma University
• Principal Investigator: Takeshi Kawarabayashi 群馬大学, 医学部, 非常勤講師 (90186156)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: アルツハイマー病 / ワクチン / 組み替え蛋白 / 認知症 / 疾患修飾療法 / アミロイド / アミロイドbeta蛋白

Outline of Final Research Achievements

We generated a transgenic plant-based vaccine, a soybean storage protein containing Amyloid-beta protein (Abeta) 4-10, named Abeta+ to prevent Alzheimer’s disease (AD). One mg of Abeta+ or control protein (Abeta-) was administered to TgCRND8 mice once a week from 9 weeks up to 58 weeks. Abeta+ immunization raised anti-Abeta oligomer antibodies. Spatial learning decline was prevented in the Abeta+ immunized group from 21weeks. Abeta oligomers decreased in TBS fractions, corresponding to an increase in high molecular weight Abeta oligomers in SDS extracts and Abeta smears in FA fraction of the Abeta+ treated group. There was significant inhibition of histological Abeta burden, especially in diffuse plaques, and suppression of microglial inflammation. No evidence of amyloid-related inflammatory angiopathy was observed. Abeta+ oral immunization could be a promising, cheap, and long-term safe disease-modifying therapy to prevent the pathological process in AD.

Free Research Field

アルツハイマー病

Academic Significance and Societal Importance of the Research Achievements

アミロイドbeta蛋白抗体によるアルツハイマー病(AD)の予防効果が示され、実用化されつつある。本邦でもAducanumabは承認審査中である。AD発症予防には認知症発症前からの長期の投与が必要と考えられているが、抗体療法は非常に高価で、注射のため侵襲的である。我々の開発した組み替えダイズによる経口免疫療法は有効で安全であり、さらに抗体に比べて安価に作成でき、大量生産も可能である。よってAD予防の有効な疾患修飾療法になりうると考えられる。製品化に向けて製薬会社との相談を行っている。