15 Participants Needed

Gene Therapy for Alzheimer's Disease

Recruiting at 4 trial locations
LC
Overseen ByLexeo Clinical Trials
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as systemic immunosuppressants, corticosteroids, monoclonal anti-amyloid therapies, and anti-coagulant medications. If you are on these medications, you may need to stop them before participating.

What data supports the effectiveness of the treatment LX1001, AAVrh.10hAPOE2 for Alzheimer's disease?

Research shows that similar gene therapy approaches using adeno-associated virus (AAV) vectors have been effective in delivering therapeutic genes to the brain, improving symptoms in Alzheimer's disease models. For example, AAV-mediated delivery of therapeutic agents has been shown to reduce amyloid plaques and improve cognitive function in animal models.12345

Is the gene therapy treatment AAVrh.10hAPOE2 safe for humans?

In studies with nonhuman primates, the AAVrh.10hAPOE2 gene therapy was found to be safe when delivered to the central nervous system, showing wide distribution with minimal surgical intervention.13567

How is the treatment LX1001 unique for Alzheimer's disease?

LX1001 is a gene therapy that uses a virus to deliver a protective gene variant, APOE2, directly into the brain, which is different from most Alzheimer's treatments that focus on reducing amyloid plaques or inflammation. This approach aims to modify genetic risk factors and potentially prevent or reverse neurological damage in patients with a high-risk APOE4 gene variant.35689

What is the purpose of this trial?

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.

Research Team

LC

Lexeo Clinical Trials

Principal Investigator

Lexeo Therapeutics

Eligibility Criteria

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.

Inclusion Criteria

Participants who agree not to post their personal data related to the study on social media.
I have been diagnosed with early or moderate Alzheimer's disease.
I haven't taken part in any experimental drug trials for the last 4 weeks.
See 6 more

Exclusion Criteria

I have no allergies to the study drug or related medications.
Prior or concurrent participation in any gene and/or cell therapy
More than 4 cerebral microhemorrhages (regardless of their anatomical location or diagnostic characterization as 'possible' or 'definite'), a single area of superficial siderosis, or evidence of a prior macro hemorrhage on screening MRI
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intrathecal administration of AAVrh.10hAPOE2 (LX1001) to assess safety and toxicity

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • LX1001
Trial Overview 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.
Participant Groups
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.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Lexeo Therapeutics

Lead Sponsor

Trials
5
Recruited
110+

Alzheimer's Drug Discovery Foundation

Collaborator

Trials
22
Recruited
3,100+

Weill Medical College of Cornell University

Collaborator

Trials
1,103
Recruited
1,157,000+

Findings from Research

A gene therapy vector delivering a wild-type copy of the PSEN1 gene has been developed, showing promise in normalizing γ-secretase function and slowing neurodegeneration in mouse models of autosomal dominant Alzheimer's disease (ADAD).
Biodistribution studies in nonhuman primates demonstrated broad expression of the PS1 protein in critical brain regions, suggesting that this approach could be effective in clinical settings for treating ADAD.
Developing a Gene Therapy for the Treatment of Autosomal Dominant Alzheimer's Disease.Moore, B., Sharma, A., Goulet, M., et al.[2023]
The developed siRNA nanocomplex effectively targets amyloid plaques in the brains of APP/PS1 transgenic mice, leading to significant reductions in BACE1 levels and amyloid plaque accumulation, comparable to wild-type mice.
This targeted gene therapy not only improved the biochemical markers of Alzheimer's disease but also rescued memory loss in the mice without causing any harmful side effects, indicating its potential as a safe and effective treatment for AD.
Small interfering RNA delivery to the neurons near the amyloid plaques for improved treatment of Alzheimer׳s disease.Guo, Q., Zheng, X., Yang, P., et al.[2020]
A novel gene transfer strategy using BBB-crossing AAV vectors successfully delivered single domain antibodies (VHHs) into the central nervous system, demonstrating potential for treating neurological disorders.
In a mouse model of Alzheimer's disease, a single dose of AAV-VHH-B9 significantly reduced BACE1 activity and led to long-term improvements in amyloid load, neuroinflammation, synaptic function, and cognitive performance over 12 months.
AAV-mediated delivery of an anti-BACE1 VHH alleviates pathology in an Alzheimer's disease model.Marino, M., Zhou, L., Rincon, MY., et al.[2022]

References

Developing a Gene Therapy for the Treatment of Autosomal Dominant Alzheimer's Disease. [2023]
Small interfering RNA delivery to the neurons near the amyloid plaques for improved treatment of Alzheimer׳s disease. [2020]
AAV-mediated delivery of an anti-BACE1 VHH alleviates pathology in an Alzheimer's disease model. [2022]
Brain-wide Cas9-mediated cleavage of a gene causing familial Alzheimer's disease alleviates amyloid-related pathologies in mice. [2023]
AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP+PS1 mice. [2021]
AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease. [2019]
Intramuscular delivery of a single chain antibody gene prevents brain Aβ deposition and cognitive impairment in a mouse model of Alzheimer's disease. [2010]
Catalytic immunoglobulin gene delivery in a mouse model of Alzheimer's disease: prophylactic and therapeutic applications. [2021]
AAV1/2-mediated CNS gene delivery of dominant-negative CCL2 mutant suppresses gliosis, beta-amyloidosis, and learning impairment of APP/PS1 mice. [2021]
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