APOE4 Alzheimer’s Disease
LX1001 / LX1020 / LX1021
Alzheimer’s disease is the leading cause of late life mental failure in humans.
- Fast Track Designation (FDA)
Alzheimer’s disease is a progressive neurodegenerative disorder that is the leading cause of cognitive decline in late adult life. It affects regions of the brain implicated in learning and memory, gradually destroying a person’s ability to remember, learn, and ultimately carry out activities of daily living. It is the sixth leading cause of mortality in the United States and the fifth leading cause of death among those aged 65 and older. It is estimated that there were 6.2 million patients living with Alzheimer’s disease in 2021 in the United States alone.
Alzheimer’s disease is characterized by a complex underlying pathology in the CNS, including accumulation of Aß plaques, abnormal phosphorylation of tau, development of tau tangles, inflammation, and progressive loss of neurons, all of which combine to precipitate a progressive decline in cognitive function. Apoplipoprotein (APOE), a lipid transport protein, is the major transporter of cholesterol in the brain and is involved in synaptic integrity and plasticity, glucose metabolism, and cerebrovascular function.
Presence of APOE4 is the most common genetic risk factor for Alzheimer’s disease. The prevalent APOE alleles are APOE4, APOE3 and APOE2, with the E4 allele increasing risk and reducing the age of onset and the E2 allele decreasing risk and markedly delaying the age of onset. APOE4 homozygous patients, individuals who have two copies of the E4 allele, are at the highest risk and are approximately fifteen times more likely to develop Alzheimer’s disease than the general population.
LX1001 is an AAV-based gene therapy candidate that is designed to express the protective APOE2 protein in the CNS of APOE4 homozygous patients to halt or slow the progression of Alzheimer’s disease.
Apolipoprotein E2 protein may act to increase amyloid beta clearance and, in that way and potentially other mechanisms, promote neuroprotection.