Gene Therapy for Alzheimer's Disease

(LEADLTFU Trial)

This trial examines the long-term safety of a gene therapy treatment for Alzheimer's disease. The treatment, LX1001 (also known as AAVrh.10hAPOE2), aims to alter certain genes to improve brain function and reduce Alzheimer's symptoms. It targets individuals with a specific genetic profile (APOE4) who received this treatment in an earlier study. Participants should have mild cognitive issues or dementia due to Alzheimer's and have previously undergone the initial gene therapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

The trial protocol does not specify whether you need to stop taking your current medications.

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Research has shown that LX1001, a gene therapy for Alzheimer's, is generally safe and well-tolerated. Earlier studies found no serious side effects and reported no cases of ARIA, a condition involving brain swelling or bleeding. Patients showed improvements in protein levels related to Alzheimer's, with greater effects at higher doses. This suggests that the treatment is not only safe but also potentially effective in addressing disease markers.¹²³⁴⁵

Most treatments for Alzheimer's disease focus on managing symptoms or slowing progression through medications like cholinesterase inhibitors and NMDA receptor antagonists. However, LX1001 is unique because it leverages gene therapy to potentially alter the disease's course itself. Researchers are excited about LX1001 because it targets the APOE4 gene, a major genetic risk factor for Alzheimer's, aiming to modify its expression and thereby reduce the risk or severity of the disease. This innovative approach offers a new mechanism of action that could lead to more effective and long-lasting outcomes compared to current treatment options.

Research shows that LX1001, a gene therapy, increases levels of a protein called APOE2 in a dose-dependent manner. This is significant because APOE2 may help protect against Alzheimer's disease. In earlier studies, patients showed improvements in certain proteins linked to Alzheimer's progression. The treatment proved safe and well-tolerated, with no cases of amyloid-related imaging abnormalities (ARIA), a possible side effect of Alzheimer's treatments. These findings suggest that LX1001 might positively change disease markers for people with Alzheimer's. Participants in this trial will be monitored for up to 260 weeks to evaluate the long-term safety of LX1001.¹²³⁵⁶