Gene Therapy for Cardiomyopathy in Friedreich's Ataxia

Not currently recruiting at 3 trial locations

Overseen By LEXEO Clinical Trials

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Lexeo Therapeutics

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Diabetes, Liver dysfunction, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy, LX2006, to determine its effectiveness for people with Friedreich's Ataxia who also have cardiomyopathy. The goal is to assess the safety and efficacy of delivering a specific gene to heart cells. Participants will receive one of three doses and be monitored over five years. Individuals diagnosed with Friedreich's Ataxia and related heart issues may be suitable candidates for this study. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I need to stop my current medications for the trial?

The trial excludes participants who are taking systemic corticosteroids or other immunosuppressive medications, so you may need to stop these if you are currently taking them. The protocol does not specify about other medications.

Is there any evidence suggesting that LX2006 is likely to be safe for humans?

Research shows that LX2006, a gene therapy for heart problems in Friedreich's Ataxia, appears safe. Studies have found no serious side effects related to the treatment so far, suggesting patients tolerate it well.

The treatment uses a virus to deliver a healthy version of the frataxin gene directly to heart cells, aiming to improve heart function. Although the study is ongoing, results so far are encouraging, with no major safety issues reported.

As this is an early-stage trial, these findings are important because they suggest the treatment does not cause serious harm in humans. However, more research is needed to confirm these results over a longer period. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cardiomyopathy in Friedreich's Ataxia?

Researchers are excited about LX2006 because it offers a new approach to treating cardiomyopathy in Friedreich's Ataxia through gene therapy. Unlike traditional treatments that primarily focus on managing symptoms, LX2006 aims to address the root cause by delivering a functional gene to correct the underlying genetic defect. This innovative mechanism could potentially halt or even reverse disease progression, offering hope for a more effective solution.

What evidence suggests that LX2006 might be an effective treatment for cardiomyopathy in Friedreich's Ataxia?

Research has shown that LX2006, a gene therapy under study in this trial, could help treat heart problems in people with Friedreich's Ataxia. This therapy uses a harmless virus to deliver a healthy version of the frataxin gene directly to heart cells. Studies have found that LX2006 is safe and leads to significant improvements in heart health. These positive changes suggest that the treatment could slow the disease's progression. Early evidence supports its safety and potential benefits for patients with this condition. ^{1 2 3 5 6}

Who Is on the Research Team?

LEXEO Clinical Trials

Principal Investigator

Lexeo Therapeutics

Are You a Good Fit for This Trial?

This trial is for individuals with Friedreich's Ataxia diagnosed before age 25 who have heart issues related to the condition. They must meet specific criteria for cardiomyopathy and antibody levels. Excluded are those with significant coronary disease, uncontrolled diabetes or psychiatric conditions, abnormal liver function, certain infections like hepatitis or HIV, unstable heart rhythms needing intervention, or on immunosuppressive drugs.

Inclusion Criteria

Your levels of specific antibodies need to be within certain ranges as outlined in the study protocol.

You have specific heart problems described in the study protocol.

I was diagnosed with Fanconi anemia before I turned 25.

Exclusion Criteria

You have a mental health condition that is not being well managed.

My diabetes is not under control.

I have heart disease not related to FA cardiomyopathy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single administration of LX2006 gene therapy, with dose escalation across cohorts

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• LX2006

Trial Overview The study tests LX2006 gene therapy at different doses in people with Friedreich's Ataxia-related cardiomyopathy. It involves a single administration of an AAV vector carrying the human frataxin gene to cardiac cells and monitors safety and effectiveness over one year, with a follow-up period extending to five years.

How Is the Trial Designed?

Group I: Cohort 1/ Cohort 2/ Cohort 3 Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Lexeo Therapeutics

Lead Sponsor

Trials

5

Recruited

110+

Published Research Related to This Trial

In a study of 48 pediatric patients with Friedreich's ataxia, 85% showed elevated left ventricular mass, indicating a common subclinical hypertrophic cardiomyopathy despite normal heart function as measured by ejection fraction.

Concentric hypertrophy was found in 44% of subjects and was specifically linked to significant diastolic and systolic dysfunction, highlighting the need for cardiac monitoring in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Subclinical Cardiomyopathy of Friedreich's Ataxia in a Pediatric Population. Plehn, JF., Hasbani, K., Ernst, I., et al.[2019]

The micro-dystrophin gene transfer using rAAVrh74.MHCK7 was found to be well tolerated in a phase 1/2a trial with four young patients, showing only mild to moderate adverse events and no serious complications over one year.

All patients demonstrated significant expression of micro-dystrophin in muscle fibers and improvements in functional measures, such as North Star Ambulatory Assessment scores and reduced creatine kinase levels, indicating potential benefits beyond standard care for Duchenne muscular dystrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial. Mendell, JR., Sahenk, Z., Lehman, K., et al.[2021]

The study developed a cardiac-specific mouse model of Friedreich's ataxia (FA) that mimics the human condition, showing normal heart function at rest but significant dysfunction under stress, which is crucial for testing potential therapies.

A single intravenous treatment with an AAV vector delivering the human frataxin gene successfully corrected the cardiac dysfunction in the mouse model, restoring heart performance to levels similar to healthy controls, indicating the potential efficacy of gene therapy for FA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stress-Induced Mouse Model of the Cardiac Manifestations of Friedreich's Ataxia Corrected by AAV-mediated Gene Therapy. Salami, CO., Jackson, K., Jose, C., et al.[2023]

AAVrh.10hFXN, an adeno-associated virus vector delivering the human frataxin gene, shows promise in treating cardiac issues in Friedreich's ataxia, with a significant improvement in heart function and mortality observed at a dose of 1.8 × 10^12 gc/kg in a mouse model.

The study identified effective dosing levels that can achieve frataxin levels comparable to healthy human heterozygotes, suggesting potential for safe and effective treatment in larger animal models, paving the way for future clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Safe and Effective Intravenous Dose of AAVrh.10hFXN to Treat the Cardiac Manifestations of Friedreich's Ataxia. Munoz-Zuluaga, C., Gertz, M., Yost-Bido, M., et al.[2023]

In a study on Friedreich ataxia, it was found that transducing only 30% of cardiomyocytes with gene therapy can still provide meaningful therapeutic effects, while full cardiac function recovery requires about 50% transduction.

The study highlights that the therapeutic benefits of gene therapy are achieved through mechanisms that maintain mitochondrial health in treated cells, and even neighboring untreated cells can experience increased survival, suggesting a broader impact of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correction of half the cardiomyocytes fully rescue Friedreich ataxia mitochondrial cardiomyopathy through cell-autonomous mechanisms. Belbellaa, B., Reutenauer, L., Monassier, L., et al.[2023]

Genome editing using zinc finger nucleases to correct the expanded GAA repeats in the FXN gene of Friedreich's ataxia (FRDA) patients significantly upregulated frataxin expression and reversed pathological changes in cardiomyocytes derived from induced pluripotent stem cells (iPSCs).

The study demonstrated that iPSC-derived FRDA cardiomyocytes exhibit distinct molecular defects associated with cardiomyopathy, which can be effectively corrected through genome editing, highlighting the potential for this approach as a future therapeutic strategy for FRDA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Excision of the expanded GAA repeats corrects cardiomyopathy phenotypes of iPSC-derived Friedreich's ataxia cardiomyocytes. Li, J., Rozwadowska, N., Clark, A., et al.[2023]

The clinical trial demonstrated that the chimeric AAV2.5 vector is safe and well tolerated in boys with Duchenne muscular dystrophy (DMD), with no cellular immune response detected against the AAV2.5 capsid.

AAV2.5 showed effective gene transfer, with recombinant AAV genomes found in all patients, indicating its potential for efficient muscle transduction and paving the way for future gene therapy applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. Bowles, DE., McPhee, SW., Li, C., et al.[2022]

Citations

1. ir.lexeotx.com ir.lexeotx.com/news-releases/news-release-details/lexeo-therapeutics-announces-positive-interim-phase-12-data

Press Release “These data provide strong evidence that LX2006 is acting as a beneficial disease-modifying treatment candidate, supporting its continued ...

2. curefa.org curefa.org/drug-development/lx2006-gene-therapy/

LX2006 Gene Therapy LX2006 is an AAV-based gene therapy candidate designed to intravenously deliver a functional frataxin gene, for the treatment of Friedreich's ataxia ...

3. ir.lexeotx.com ir.lexeotx.com/news-releases/news-release-details/lexeo-therapeutics-announces-progress-fda-discussions

Press Release Updated interim clinical data from both ongoing Phase I/II studies of LX2006 continue to show encouraging safety and efficacy, exceeding the ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05445323?term=AREA%5BNCTIdSearch%5D(NCT05445323)&rank=1

Gene Therapy for Cardiomyopathy Associated With ... This is a Phase 1/2, open-label, dose-ascending, multicenter study of the safety and efficacy of LX2006 for participants who have Friedreich's Ataxia with ...

5. neurologylive.com neurologylive.com/view/gene-therapy-lx2006-positively-impacts-cardiac-biomarkers-friedreich-ataxia

Gene Therapy LX2006 Positively Impacts Cardiac ... LX2006 shows safety, tolerance, and significant improvements in cardiac biomarkers in FA cardiomyopathy, progressing to higher dose cohorts.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05445323

Study Details | NCT05445323 | Gene Therapy for ... The primary objective of this dose escalation study is to assess the safety and tolerability of three ascending doses of LX2006 in patients with FA-associated ...