What is the mechanism of action of this treatment?

Leber Congenital Amaurosis (LCA) treatments, particularly gene therapy, work by delivering a functional copy of the defective gene directly to retinal cells. For example, the OPGx-001 trial uses viral vectors to introduce a healthy LCA5 gene into the retina. This mechanism is vital as it targets the root cause of the disease, aiming to restore normal gene function and potentially halt or reverse vision loss, offering significant and lasting improvements for patients.

What side effects are associated with this type of intervention?

Gene therapy for Leber Congenital Amaurosis, such as the delivery of the functional LCA5 gene to retinal cells, can have several side effects. Commonly reported side effects include mild to moderate inflammation, which can be managed with corticosteroids. Other potential side effects include retinal detachment, increased intraocular pressure, and cataract formation. In some cases, there may be an immune response to the viral vector used to deliver the gene. Careful dose optimization and monitoring are essential to minimize these risks.

What prior FDA approvals exist?

The FDA has approved gene therapy for Leber Congenital Amaurosis, specifically targeting mutations in the RPE65 gene. Luxturna (voretigene neparvovec-rzyl) is an FDA-approved gene therapy that delivers a functional copy of the RPE65 gene to retinal cells, improving vision in patients with LCA caused by RPE65 mutations. This treatment is similar in approach to the OPGx-001 trial, which aims to deliver a functional LCA5 gene to retinal cells.

What other types of research exist?

Promising alternatives to OPGx-001 for LCA patients include: 1) AAV-based gene therapies targeting other LCA-related genes such as RPE65, CEP290, and GUCY2D, which are in various stages of clinical trials. 2) CRISPR/Cas9 gene editing techniques aimed at correcting specific mutations causing LCA. 3) Stem cell-based therapies that aim to replace damaged retinal cells. These approaches are being actively researched and have shown potential in early studies.

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Gene Therapy

Gene Therapy for Leber Congenital Amaurosis

Phase 1 & 2

Recruiting

Research Sponsored by Opus Genetics, Inc

Eligibility Criteria Checklist

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

Must have

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new gene therapy injected under the retina to help people with a specific genetic eye condition that causes vision loss. The therapy aims to replace faulty genes with healthy ones to improve vision. Mutations in the RPE65 gene are one of the causes of RP and Leber congenital amaurosis (LCA), a form of RP present at birth.

Who is the study for?

Adults with inherited retinal degeneration due to LCA5 gene mutations, who have visual acuity less than 20/80 and detectable photoreceptors. Candidates must be able to undergo surgery, follow post-surgery instructions, use effective contraception if of childbearing potential, and commit to the study protocol.

What is being tested?

The trial is testing a subretinal gene therapy called OPGx-001 for safety and initial effectiveness in treating vision loss caused by LCA5-associated retinal degeneration. It involves surgical delivery of the AAV8.hLCA5 gene therapy directly into the retina.

What are the potential side effects?

Potential side effects may include typical risks associated with eye surgery such as discomfort or infection at the injection site, inflammation inside the eye, changes in intraocular pressure or cataract formation. Gene therapy-specific reactions could also occur.

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

Change in retinal thickness

Secondary study objectives

Change from baseline to month 12 in retinal sensitivity

Change from baseline to month 12 transient pupillary light reflexes (TPLR)

Other study objectives

Chromatic referential looking

Full-field chromatic sensitivity testing (FST)

Kinetic perimetry

+2 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Dose Group 3Experimental Treatment1 Intervention

A single, unilateral, subretinal injection of high dose (1E11 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of a high dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents).

Group II: Dose Group 2Experimental Treatment1 Intervention

A single, unilateral, subretinal injection of an intermediate dose (3E10 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of an intermediate dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents).

Group III: Dose Group 1Experimental Treatment1 Intervention

A single, unilateral, subretinal injection of low dose (1E10 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of a low dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents).

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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

Leber Congenital Amaurosis (LCA) treatments, particularly gene therapy, work by delivering a functional copy of the defective gene directly to retinal cells. For example, the OPGx-001 trial uses viral vectors to introduce a healthy LCA5 gene into the retina. This mechanism is vital as it targets the root cause of the disease, aiming to restore normal gene function and potentially halt or reverse vision loss, offering significant and lasting improvements for patients.