Commentary

Video

Promising Innovative Gene Therapy for APOE4 Homozygous Alzheimer Disease: R. Nolan Townsend; Sandi See Tai, MD; Kim G. Johnson, MD

A trio of experts talked about Lexeo Therapeutics’ LX1001 gene therapy trial that demonstrated promising safety and biomarker effects in patients with early-stage Alzheimer disease. [WATCH TIME: 5 minutes]

WATCH TIME: 5 minutes

“[Patients with] APOE4 homozygotes have no good treatment options right now, and this trial offers a potential treatment that provides hope for patients and their families.”

Alzheimer disease (AD) has a known strong genetic risk linked to apolipoprotein E (APOE) polymorphisms. Studies show that APOE4 homozygotes face a 14.5-fold higher risk of late-onset AD than APOE3 homozygotes, and APOE2/E4 heterozygotes have a 2.6-fold increased risk, indicating a potential protective role for APOE2. LX1001 (Lexeo Therapeutics) is an investigational adeno-associated viral vector gene therapy designed to deliver the APOE2 gene into the central nervous system of patients with APOE4 homozygous AD, potentially converting their profile to APOE2/E4 and slowing disease progression.1

Newly presented interim data from the ongoing phase 1/2, open-label, dose-finding study (NCT03634007) demonstrated that LX1001 was generally safe and well tolerated, resulting in a dose- and time-dependent effect on APOE2 expression. Presented at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference, held October 29 to November 1, in Madrid, Spain, additional findings showed that a reduction in several cerebrospinal fluid (CSF) AD tau biomarkers and changes on Tau PET suggested a treatment effect of LX1001 on tau, a which researchers noted as a critical component in the pathobiology of AD.2

At CTAD 2024, R. Nolan Townsend, chief executive officer at Lexeo, coauthor Sandi See Tai, MD, chief development officer at Lexeo, and lead author Kim G. Johnson, MD, the division chief of memory disorders at Duke University, sat down with NeurologyLive® to further discuss some of the key safety findings from the trial. During the conversation, the trio also talked about how the APOE2 gene delivery impacted amyloid and tau biomarkers in trial participants, as observed in the study findings. Additionally, the experts spoke about the significance of targeting APOE4 homozygotes with gene therapy in the AD treatment landscape.

Click here for more coverage of CTAD 2024.

REFERENCES
1. Johnson K, et al. Safety and Preliminary Efficacy of AAV Gene Therapy (LX1001) in Patients with APOE4 Homozygote Alzheimer’s Disease – Interim Data from a Phase 1/2, Open-Label, 52-Week, Multicenter Study. Presented at: 2024 CTAD; October 29-November 1; Madrid, Spain. Abstract 486.
2. Lexeo Therapeutics Announces Positive Interim Data for LX1001, First-Ever Gene Therapy to Impact the Underlying Genetic Cause of APOE4-Associated Alzheimer’s Disease, at the Clinical Trials on Alzheimer’s Disease (CTAD) Conference. News Release. Lexeo Therapeutics. Published October 30, 2024. Accessed October 20, 2024.
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