What is the mechanism of action of this treatment?

The most common treatments for Alzheimer's Disease often focus on altering genetic material to address the underlying causes of the disease. Gene therapy, for instance, targets specific genes like APOE, APP, PSEN1, and PSEN2, which are known to influence Alzheimer's. By modifying these genes, the therapy aims to reduce the production of amyloid-beta plaques or enhance neuronal function. This approach is significant for Alzheimer's patients as it targets the root cause of the disease, potentially slowing or halting its progression rather than merely alleviating symptoms.

What side effects are associated with this type of intervention?

Common treatments for Alzheimer's Disease include cholinesterase inhibitors (e.g., donepezil, rivastigmine) and NMDA receptor antagonists (e.g., memantine). These treatments can cause side effects such as nausea, vomiting, diarrhea, muscle cramps, and dizziness. Gene therapy, which is being studied for Alzheimer's, may have side effects including immune reactions, infections, and potential off-target genetic effects. As with any new treatment, the long-term side effects of gene therapy are still being evaluated.

What prior FDA approvals exist?

The FDA has approved several treatments for Alzheimer's Disease, primarily focusing on symptom management rather than altering genetic material. Cholinesterase inhibitors like donepezil, rivastigmine, and galantamine, as well as the NMDA receptor antagonist memantine, are commonly used. Recently, aducanumab, a monoclonal antibody targeting amyloid-beta plaques, received approval, marking a shift towards disease-modifying therapies. While gene therapy for Alzheimer's is still in experimental stages, these approved treatments provide a foundation for understanding and potentially enhancing future genetic interventions.

What other types of research exist?

Promising novel alternatives to gene therapy for Alzheimer's Disease patients in 2024 include: 1) Antisense oligonucleotide therapy, which targets and modulates specific RNA sequences to reduce the production of harmful proteins. 2) RNA interference (RNAi) therapies, such as patisiran, which silence specific genes involved in disease progression. 3) Small molecule inhibitors, like BACE inhibitors, which prevent the formation of amyloid plaques. 4) Immunotherapy approaches, including monoclonal antibodies targeting amyloid-beta and tau proteins. 5) Lifestyle and dietary interventions, which focus on reducing risk factors and improving overall brain health.

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Gene Therapy

Gene Therapy for Alzheimer's Disease

Phase 1 & 2

Waitlist Available

Research Sponsored by Lexeo Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Clinical diagnosis of mild cognitive impairment due to Alzheimer's disease or mild to moderate dementia due to Alzheimer's disease

APOE4 homozygotes

Must not have

Individuals who cannot undergo study-related procedures without general anesthesia (other than who need general anesthesia for the gene therapy administration)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a gene therapy injected into brain fluid for Alzheimer's patients with two APOE4 genes. The therapy aims to change a harmful brain protein to a less harmful version, potentially improving symptoms. Gene therapy is rapidly emerging as a powerful therapeutic strategy for a wide range of neurodegenerative disorders, including Alzheimer's disease.

Who is the study for?

This trial is for APOE4 homozygotes with mild to moderate Alzheimer's-related cognitive impairment or dementia, who can consent and agree not to share study details on social media. Participants should not be on experimental meds or have active infections like hepatitis or HIV, and must avoid pregnancy during the study.

What is being tested?

The trial tests LX1001 gene therapy in an open label, dose-ranging format for those diagnosed with varying stages of Alzheimer's disease due to APOE4 homogeneity. It aims to assess its safety and effectiveness in improving cognitive functions.

What are the potential side effects?

While specific side effects are not listed here, gene therapies like LX1001 may cause immune reactions, injection site reactions, headache, nausea, fatigue and potential long-term risks which will be monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with early or moderate Alzheimer's disease.

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I have two copies of the APOE4 gene.

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I do not have any active infections, including hepatitis or HIV.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I don't need general anesthesia for procedures, except for the gene therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Proportion of participants with treatment-emergent adverse events and serious adverse events

The proportion of participants with treatment-emergent adverse events and serious adverse events at each dosage

Secondary study objectives

Assess the levels of CSF biomarkers

Change from baseline in APOE2-APOE4 isoforms

Change from baseline in Clinical Dementia Rating Global and Sum of Boxes (CDR-SB)

+11 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Cohort 4: 1.4 x 10^14 gc (fixed dose)Experimental Treatment1 Intervention

Participants will receive 1.4 x 10\^14 gc (fixed dose; approximately 3.4 × 10\^11 gc/mL CSF based on an average CSF volume of 409 mL) of LX1001.

Group II: Cohort 3: 1.4 x 10^11 gc/mL CSFExperimental Treatment1 Intervention

Participants will receive 1.4 x 10\^11 gc/mL CSF of LX1001.

Group III: Cohort 2: 4.4 x 10^10 gc/mL CSFExperimental Treatment1 Intervention

Participants will receive 4.4 x 10\^10 gc/mL CSF of LX1001.

Group IV: Cohort 1: 1.4 x 10^10 gc/mL CSFExperimental Treatment1 Intervention

Participants will receive 1.4 x 10\^10 gc/mL CSF of LX1001.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

LX1001

2019

Completed Phase 2

~20

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Alzheimer's Disease often focus on altering genetic material to address the underlying causes of the disease. Gene therapy, for instance, targets specific genes like APOE, APP, PSEN1, and PSEN2, which are known to influence Alzheimer's. By modifying these genes, the therapy aims to reduce the production of amyloid-beta plaques or enhance neuronal function. This approach is significant for Alzheimer's patients as it targets the root cause of the disease, potentially slowing or halting its progression rather than merely alleviating symptoms.