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Table 1 A selection of APOE based therapeutics used in rodent models and and clinical testing

From: Therapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease

Drug

Rationale

Developed by

Reference/Clinical Trial Identifier

CS-6253

Increase APOE lipidation by activating ABCA1

Tel Aviv University/Artery Therapeutics

Ref 125

CN-105

APOE mimetic

CereNova/AegisCN LLC

Phase1: NCT02670824 (ICH); Ref 231

Phthalazinones, pyrazolines

Small molecule structure-correctors

Gladstone Institute/E-Scape bio

Ref 132

APOE antibody

Targeting non-lipidated APOE

Washington University/Denali therapeutics

Ref 99

Anti-sense oligonucleotide

Reduce expression of APOE4

Washington University/Ionis

Ref 104

Gene Therapy

Biological: AAVrh.10 hAPOE2 vector

Cornell University

Phase 1: NCT03634007

Bexarotene

Alter APOE production, APOE lipidation and Aβ clearance

ReXceptor Inc. and C2N

Phase 1: NCT02061878

Outcome: No change in Aβ; increased CSF APOE

Cleveland Clinic

Phase 2:NCT01782742

Outcome: No benefit in APOE4 patients; Ref 114

Probucol

Cholesterol lowering drug

McGill University/Douglas Hospital Research Center

Phase1/2: NCT02707458 Ref 232

AGB101

Reduce APOE4-dependent abnormal hippocampal network activity

Medical College of Wisconsin

Phase 2: NCT03461861 Ref 233

Rosiglitazone

Anti-diabetic (APOE allele dependent response)

GlaxoSmithKline

Phase3: NCT00348140

Outcome:No effect on mild to moderate AD;

Ref 234

Epigallocatechin gallate (EGCG) + multimodal intervention (diet, exercise)

Correct APOE4-dependent cognitive decline

Parc de Salut Mar

Recruiting: NCT03978052. No direct references found but see Ref 235

Exercise

Relationship of APOE4 to CBF and blood-based biomarkers (IGF-1, VEGF, BDNF)

University of Kansas Medical Center

Recruiting:

NCT04009629

Ref 236