In a recent press release, biotechnology and gene therapy company LEXEO Therapeutics (“LEXEO”) shared that its gene therapy LX1001 received Fast Track designation from the FDA. Overall, LX1001 is designed to treat patients with apolipoprotein E4 (APOE4)-associated Alzheimer’s disease. Considering how heavily APOE4 is thought to increase the risk of developing late-onset Alzheimer’s disease, this investigational gene therapy could fulfill an unmet need.

LX1001

So what is LX1001? The drug uses adeno-associated viral (AAV) vectors to deliver the therapy to the central nervous system (CNS). As described by AskBio:

Simply put, AAV is transformed from a naturally occurring virus into a delivery mechanism for gene therapy [by replacing the] viral DNA…with new DNA. The AAV vector is then used to deliver normal copies of genes to the right tissues or organs in the body, but it now delivers the therapy that has been engineered into it.

Currently, researchers are evaluating LX1001 for APOE4-associated Alzheimer’s disease in a Phase 1 clinical trial. 15 patients will enroll. During the study, researchers will evaluate the safety, efficacy, toxicity, and maximum tolerated dose.

APOE4-Associated Alzheimer’s disease

According to the National Institute on Aging:

having a genetic variant of the apolipoprotein E (APOE) gene on chromosome 19 does increase a person’s risk [of developing late-onset Alzheimer’s disease]. The APOE gene is involved in making a protein that helps carry cholesterol and other types of fat in the bloodstream.

There are multiple types of APOE, including APOE2, APOE3, and APOE4. The National Institute on Aging continues:

APOE2 is relatively rare and may provide some protection against the disease, [while] APOE3, the most common allele, is believed to play a neutral role in the disease—neither decreasing nor increasing risk. APOE4 increases the risk of Alzheimer’s disease and is also associated with an earlier age of disease onset.

While inheriting an APOE4 allele does not mean you will develop Alzheimer’s disease, it does increase the risk.

Fast Track Designation for LX1001

As described above, APOE2 is thought to have some sort of protective quality against Alzheimer’s disease. Thus, LX1001 works by delivering the APOE2 gene to the CNS, conferring protection against APOE4. Now, the therapy has been granted Fast Track designation. Fast Track designation is specifically granted by the FDA:

to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier.

The FDA continues:

Determining whether a condition is serious is a matter of judgment, but generally is based on whether the drug will have an impact on such factors as survival, day-to-day functioning, or the likelihood that the condition, if left untreated, will progress from a less severe condition to a more serious one. Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially better than available therapy.

Alzheimer’s Disease

Alzheimer’s disease, a progressive neurodegenerative disease, is thought to be caused by a combination of environmental and lifestyle factors, as well as genetics. As explained, APOE4 increases the risk. In any case, neurons disconnect and die, causing neurodegeneration. Over time, the severity of Alzheimer’s disease increases, leaving people unable to carry out daily tasks. Risk factors include age (65+), a family history of Alzheimer’s disease, prior head trauma, poor sleeping and exercise habits, and being female. Symptoms and complications include:

• Progressively worsening memory loss
• Confusion and disorientation
• Decreased or poor judgment
• Difficulty remembering recently learned information
• Changes in mood and behavior
• Inability to plan or complete familiar tasks
• Difficulty swallowing, speaking, or walking
• Unfounded suspicion towards family, friends, or caregivers
• Malnutrition and dehydration
• Aspiration
• Pneumonia

Learn more about Alzheimer’s disease here.