According to information from the National Institute of Health, one in nine elderly people in the U.S. will be affected by Alzheimer’s disease (AD). A recent article in the Globe Newswire reported that the risk of developing late-onset AD is increased fifteenfold for people who inherited the APOE4 gene.
It is estimated that about twenty-five percent of the population carry one copy of APOE4, while about two to three percent carry two copies. Conversely, the APOE2 gene offers some protection from AD.
As of yet, no FDA-approved disease-modifying treatments exist.
About LX1001
LX1001 is being evaluated in an ongoing Phase ½ trial and has previously been granted FDA’s Fast Track designation.
The treatment involves LX1001, an Adeno-associated virus-based one-time gene therapy that delivers the protective APOE2 gene into the central nervous system (CNS) to treat APOE4-associated AD.
Dr. Jay Barth, Executive VP of LEXEO, said that initial data shows a reduction in cerebrospinal fluid biomarkers (disease indicators). Dr. Barth further stated that these declines are indications of the therapeutic potential of LX1001 for APOE4-associated AD. To date, there have been no severe adverse events.
About the Trial
Fifteen evaluable patients, fifty years or older, participated in the Phase 1/2 dose-ranging study analyzing the tolerability and safety of LX1001. Each patient had two copies of the APOE4 matching genes (allele).
Clinical diagnoses necessary for enrollment were mild cognitive impairment or dementia. Evidence of cerebrospinal fluid (CSF) biomarkers and amyloid plaques associated with AD were also required.
Results of Cohort 1 Phase 1/2
Secondary end results involved converting CSF from the APOE4 profile to the protective APOE4/E2 profile.
Four patients were evaluated. Two patients were visited for data collection at three months, and two patients were visited at twelve months. Increases were seen in CSF APOE2 from baseline at follow-up visits.
About P-Tau and T-Tau
The widely accepted P-Tau and T-tau protein levels are recognized as biomarkers reflecting pathological changes that take place in the brains of AD patients. Tau proteins are known to accumulate as part of the neurodegenerative process.
Therefore, another positive result of the trial was the decline in CSF biomarkers of P-tau and T-tau protein levels in two patients (cohort 2) through month twelve.
Additional data from both cohorts will be presented in the latter part of this year.
New York-based LEXEO Therapeutics is focused on the central nervous system and genetically defined cardiovascular diseases that affect rare disease populations.
