Gene Therapy for Retinoschisis

No longer recruiting at 1 trial location
PS
HE
CA
Overseen ByCatherine A Cukras, M.D.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a gene therapy for individuals with X-linked juvenile retinoschisis (XLRS), a condition caused by changes in the RS1 gene that lead to vision loss. Researchers seek to determine if introducing a healthy RS1 gene into eye cells can restore normal function and improve vision. Participants will receive the gene therapy (RS1 AAV Vector) through an injection into the eye and will be monitored for safety and effectiveness. Adults with a confirmed RS1 gene mutation and significant vision impairment in one eye may be eligible to participate. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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

The trial requires that you stop taking systemic carbonic anhydrase inhibitors and biologic immunosuppressive agents at least three months before starting. If you are on any medication that prevents safe administration of study drugs, you may also need to stop those. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that the AAV-RS1 vector is safe for humans?

Research has shown that the RS1 AAV vector, a gene therapy treatment, has been tested for safety in people with X-linked retinoschisis (XLRS). Studies indicate that this therapy is generally well-tolerated. In one study, the treatment was administered directly to the retina, and participants did not report any major safety issues. Another study found that the treatment was safe and well-tolerated when injected into the eye. These findings support the continued development of this gene therapy as a potential treatment for XLRS.12345

Why are researchers excited about this study treatment for retinoschisis?

Unlike the standard treatments for retinoschisis, which often involve supportive measures like monitoring or, in some cases, surgery, the RS1 AAV Vector gene therapy offers a novel approach. This treatment uses a viral vector to deliver a healthy copy of the RS1 gene directly to the eye, potentially addressing the root cause of the condition rather than just managing its symptoms. Researchers are excited because this method could lead to long-term vision improvement by directly targeting the genetic defect, offering hope for a more effective and lasting solution.

What evidence suggests that the RS1 AAV Vector might be an effective treatment for X-linked juvenile retinoschisis?

Research has shown that adding a healthy RS1 gene to eye cells might help treat X-linked juvenile retinoschisis (XLRS). Studies have found that the AAV-RS1 vector, which combines the gene with a virus, can enhance eye cell function by producing normal retinoschisin. In animal studies, this gene therapy improved the retina's structure and function. Early human trials focused on safety and suggested it might help maintain or improve vision. This trial will test different dosages of the RS1 AAV Vector to determine its effectiveness in repairing broken connections in the retina, potentially slowing or stopping vision loss.12567

Who Is on the Research Team?

LA

Laryssa A Huryn, M.D.

Principal Investigator

National Eye Institute (NEI)

Are You a Good Fit for This Trial?

Adults over 18 with X-linked juvenile retinoschisis (XLRS), a specific eye condition, and vision of 20/63 or worse in one eye. Participants must have an RS1 gene mutation confirmed by genetic testing, be able to follow the study protocol and agree to use effective contraception.

Inclusion Criteria

I agree not to get live vaccines before and after receiving the treatment.
I can follow the study's treatment, tests, procedures, and visits.
One of my eyes meets the study's requirements.
See 4 more

Exclusion Criteria

I have a condition that makes it risky for me to take steroids or similar medications.
My kidney function is not normal.
Participant has a known allergy to fluorescein dye or other contraindications to obtaining a fluorescein angiogram
See 15 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
2 visits (in-person)

Treatment

AAV-RS1 vector is injected into the study eye to introduce a healthy RS1 gene

1 day
1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after gene transfer

18 months
10 visits (in-person)

Long-term follow-up

Participants are monitored yearly for safety and effectiveness

Up to 15 years
4 visits (in-person), yearly phone contact

What Are the Treatments Tested in This Trial?

Interventions

  • RS1 AAV Vector
Trial Overview The trial is testing the safety of a new treatment involving injecting a healthy RS1 gene into the eye using a virus vector called AAV-RS1. The goal is to see if this can help produce healthy retinoschisin protein for better retina function.
How Is the Trial Designed?
6Treatment groups
Experimental Treatment
Group I: Cohort 6Experimental Treatment1 Intervention
Group II: Cohort 5Experimental Treatment1 Intervention
Group III: Cohort 4Experimental Treatment1 Intervention
Group IV: Cohort 3Experimental Treatment1 Intervention
Group V: Cohort 2Experimental Treatment1 Intervention
Group VI: Cohort 1Experimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

VegaVect, Inc.

Lead Sponsor

Trials
1
Recruited
10+

National Eye Institute (NEI)

Collaborator

Trials
572
Recruited
1,320,000+

Citations

Retinal AAV8-RS1 Gene Therapy for X-Linked RetinoschisisThis study evaluated the safety and tolerability of ocular RS1 adeno-associated virus (AAV8-RS1) gene augmentation therapy to the retina of participants ...
Study of RS1 Ocular Gene Transfer for X-linked RetinoschisisOutcome Measures: The primary outcome is the safety of ocular AAV-RS1 vector as determined from assessment of retinal function, ocular structure and ...
AAV2/4-RS1 gene therapy in the retinoschisin knockout ...AAV2/4-RS1 shows promise for improving retinal phenotype in the Rs1-KO mouse model. Subretinal delivery was superior to intravitreal. Topical brinzolamide did ...
Retinal organoids with X-linked retinoschisis RS1 (E72K ...Data indicates that the AAV-RS1 vector can sustain the expression of RS1 for at least nine months [24,25,26]. Clinical trials were initiated ...
Long-term functional and structural outcomes in X-linked ...Here, we report the long-term functional and structural outcomes of XLRS and the relevance of RS1 genotypes to the visual prognosis of affected individuals.
Ocular and systemic safety of a recombinant AAV8 vector ...These studies indicate that IVT administration of AAV8-scRS/IRBPhRS is safe and well tolerated and support its advancement into a phase 1/2a clinical trial for ...
Atsena Therapeutics Announces Positive Clinical Data ...A Phase I/II clinical trial evaluating subretinal injection of ATSN-201 for the treatment of X-linked retinoschisis (XLRS).
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