公开(公告)号：US12285440B2

公开(公告)日：2025-04-29

申请号：US17694630

申请日：2022-03-14

Applicant: Massachusetts Institute of Technology

Inventor： Joel Blanchard ,  Manolis Kellis ,  Li-Huei Tsai ,  Jose Davila Velderrain ,  Leyla Akay ,  Djuna Von Maydell ,  Audrey Effenberger ,  Matheus Victor

IPC: A61K31/724 ,  A61P25/28

Abstract: The present disclosure provides methods of inhibiting amyloid synthesis in a subject using cyclodextrin and analogs thereof. Small molecules (cyclodextrin) reverse APOE4-associated cholesterol phenotypes and lead to significantly improved myelination both human in vitro cultures and APOE4 targeted replacement mice. This demonstrates that APOE4 alters cholesterol synthesis and transport in oligodendrocytes which impairs myelination. Collectively, this work uncovers a pathogenic role of APOE4 in oligodendrocytes and myelination and enables therapeutic opportunities for Alzheimer's Disease.

公开(公告)号：US20220288104A1

公开(公告)日：2022-09-15

申请号：US17694630

申请日：2022-03-14

Applicant: Massachusetts Institute of Technology

Inventor： Joel Blanchard ,  Manolis Kellis ,  Li-Huei Tsai ,  Jose Davila Velderrain ,  Leyla Akay ,  Djuna Von Maydell ,  Audrey Effenberger ,  Matheus Victor

IPC: A61K31/724 ,  A61P25/28

Abstract: The present disclosure provides methods of inhibiting amyloid synthesis in a subject using cyclodextrin and analogs thereof. Small molecules (cyclodextrin) reverse APOE4-associated cholesterol phenotypes and lead to significantly improved myelination both human in vitro cultures and APOE4 targeted replacement mice. This demonstrates that APOE4 alters cholesterol synthesis and transport in oligodendrocytes which impairs myelination. Collectively, this work uncovers a pathogenic role of APOE4 in oligodendrocytes and myelination and enables therapeutic opportunities for Alzheimer's Disease.