Researchers Close in on Alzheimer’s Disease As FDA Grants Fast Track Designation to LX1001

Alzheimer’s disease is the primary cause of the progressive decline of cognitive function in the elderly. It is characterized by underlying complications in the central nervous system (CNS). To date, no treatments are available that have been approved to modify or halt Alzheimer’s disease.

According to a recent article in Biospace, the APOE gene is involved with the production of the apolipoprotein E (APOE) gene, which is the primary cholesterol transporter in the brain. APOE has three forms (alleles):

  • APOE ε4 which raises the risk of Alzheimer’s
  • APOE ε3 considered being a neutral risk
  • APOE ε2 is somewhat rare but appears to lower the risk of the Alzheimer’s

Everyone inherits two forms of APOE, one from each of their biological parents.

Evaluating the Risk

A group of researchers set out to gain a better understanding of the risk associated with APOE ε2 in Alzheimer’s disease. They based their estimates on 4,018 Alzheimer’s cases of dementia obtained from autopsies. Additionally, data on 989 cases used as controls for the study were provided by the Alzheimer’s Consortium with the cooperation of the NIA.

Knowing the rarity of APOE ε2, the researchers were not surprised to find only twenty-four cases with two copies of APOE ε2. When compared to the other genotypes, people exhibiting two copies of APOE ε2 are at minimal risk for Alzheimer’s disease.

Individuals with two copies of APOE ε4, however, are facing about fifteen times more risk than the average individual.

About LX1001

LX1001 is currently the only gene therapy developed with the potential to remedy Alzheimer’s underlying genetics.

It is an AAV non-enveloped virus surrounded by a protein coating. The therapy is a one-time treatment that delivers the APOE2 gene into the central nervous system of APOE4 Alzheimer’s patients.

LX1001 is being evaluated in a dose-escalation Phase 1/2 trial. The FDA has recognized the treatment by granting LX1001 a Fast Track designation.

About Phase 1/2 Clinical Trial

The clinical trial is a dose ascending study involving three groups (cohorts) evaluating the tolerability and safety of LX1001.

The investigators have begun to enroll patients who have been clinically diagnosed with mild cognitive impairment or mild to moderate dementia. Initially, fifteen patients fifty years or older who have two copies of the APOE4 gene will be enrolled.

Enrollment is also contingent upon patients having amyloid plaques and cerebral spinal fluid (CSF) biomarkers associated with Alzheimer’s disease. P-tau and T-tau levels of protein are well-accepted biomarkers that reveal changes in the brains of Alzheimer’s patients. Numerous studies have also recognized Aβ42, p-tau, and t-tau as identifying the potential for cognitive impairment in people at risk for Parkinson’s disease.

The primary endpoint of the trial is the increase in dosing for the three groups (cohorts). The secondary endpoint is to evaluate the conversion of CSF from the APOE4 profile to the APOE4/E2 profile as well as CSF biomarkers.

Initial Trial Results

The researchers reported that in the low-dose group, LX1001 expressed the protective APOE2 gene in the central nervous system and lessened certain Alzheimer’s-related biomarkers. There were no severe adverse events to date. This is an indication of the treatment’s favorable tolerability.

Data from the mid-dose group and a twelve-month follow-up from the low-dose cohort will be published during the latter part of 2022.

About the Company

LEXEO Therapeutics, based in New York, targets the central nervous system and cardiovascular diseases affecting both prevalent and rare disease patient populations. LEXEO is associated with several other notable academic laboratories.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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