Gene Therapy for Retinitis Pigmentosa

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bionic Sight LLC

Disqualifiers: Prior AAV therapy, Nystagmus

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a modified virus that carries a light-sensitive gene to help people with vision problems. The virus delivers this gene to eye cells, making them respond to light and potentially improving vision.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment BS01, BS01, ChronosFP for retinitis pigmentosa?

Research shows that gene therapy can effectively preserve vision in retinitis pigmentosa, even when started at later stages of the disease. Additionally, the Chronos protein used in optogenetic gene therapy has been shown to be effective and safe in preclinical trials, suggesting potential benefits for patients with retinal degenerative diseases. ^{1 2 3 4 5}

Is gene therapy for retinitis pigmentosa safe for humans?

Gene therapy for retinitis pigmentosa has been tested in humans and animals, showing no major safety concerns. In one human trial, some patients experienced inflammation that responded to steroids, but overall, the treatment was well tolerated. ^{1 5 6 7 8}

What makes the treatment BS01 unique for retinitis pigmentosa?

BS01, also known as ChronosFP, is unique because it uses optogenetic gene therapy, which involves using light-sensitive proteins to restore vision in patients with retinal degenerative diseases like retinitis pigmentosa. This approach is different from traditional treatments as it directly targets the genetic cause of the disease and has shown promise in preclinical trials for being effective and well-tolerated. ^{1 2 5 6 9}

Research Team

Sheila Nirenberg, PhD

Principal Investigator

Bionic Sight LLC

Eligibility Criteria

This trial is for individuals with confirmed retinitis pigmentosa who have very limited vision, described as 'bare light perception', in at least one eye. It's not open to those who've previously received any AAV gene therapy or have large amplitude nystagmus, which is a condition where the eyes make repetitive, uncontrolled movements.

Inclusion Criteria

You can only see very minimal light with at least one eye.

I have been diagnosed with retinitis pigmentosa.

Exclusion Criteria

I have never received AAV gene therapy before.

I experience severe involuntary eye movements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BS01, a recombinant adeno-associated virus vector expressing ChronosFP, in a dose escalation study

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• BS01

Trial Overview The study involves BS01, a genetic treatment using a modified virus to deliver genes into cells of the eye. This early-phase trial will test different doses to see how safe it is and what effects it has on patients' vision.

Participant Groups

Group I: Cohort 4 Experimental Treatment 1 Intervention

BS01 Cohort4 dose

Group II: Cohort 3 Experimental Treatment 1 Intervention

BS01 Cohort 3 dose

Group III: Cohort 2 Experimental Treatment 1 Intervention

BS01 Cohort 2 dose

Group IV: Cohort 1 Experimental Treatment 1 Intervention

BSO1 Cohort 1 dose

Who Is Running the Clinical Trial?

Bionic Sight LLC

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

In a mouse model of retinitis pigmentosa (RP), gene therapy was able to halt degeneration and restore function when administered at early, mid, or late stages of the disease, showing that treatment can be effective even after disease onset.

The study highlights a broad therapeutic time window for gene therapy in RP, suggesting that patients diagnosed after significant photoreceptor loss can still benefit from treatment, emphasizing the need to improve transduction efficiency for better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Halting progressive neurodegeneration in advanced retinitis pigmentosa. Koch, SF., Tsai, YT., Duong, JK., et al.[2018]

In a mouse model of retinitis pigmentosa, gene therapy successfully restored function and structure of photoreceptor cells even when treatment was administered at an advanced disease stage, showing sustained efficacy for at least 1 year.

These findings suggest that retinal gene therapy could be a viable treatment option for patients with retinitis pigmentosa, even after significant degeneration has occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Success of Gene Therapy in Late-Stage Treatment. Koch, SF., Tsang, SH.[2019]

Both patients with PRPF31-related retinitis pigmentosa experienced similar clinical courses, with early onset of night blindness and relatively preserved visual acuity into their 30s, but significant deterioration of their visual fields starting in their teens.

Genetic analysis confirmed that mutations in the PRPF31 gene were responsible for their autosomal dominant retinitis pigmentosa, highlighting the importance of genetic testing in understanding the progression of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term clinical course of 2 Japanese patients with PRPF31-related retinitis pigmentosa. Kurata, K., Hosono, K., Hotta, Y.[2018]

The study followed 46 individuals with PRPF31-related retinitis pigmentosa (RP11) and found that the median age of disease onset was 10 years, with a median follow-up of 8 years, highlighting the early onset and long-term progression of the disease.

Visual field areas deteriorated significantly faster than visual acuity, with legal blindness typically occurring at a median age of 57 years, emphasizing the need for careful monitoring of visual field changes in patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease progression of retinitis pigmentosa caused by PRPF31 variants in a Nordic population: a retrospective study with up to 36 years follow-up. Lisbjerg, K., Bertelsen, M., Lyng Forman, J., et al.[2023]

Optogenetic gene therapy using the AAV2 vector and Chronos protein has shown promising efficacy in restoring vision in preclinical models, with effective results observed across various doses and light intensities.

Safety assessments in multiple animal models (mice, rats, and nonhuman primates) indicated that the treatment was well tolerated, with no significant adverse effects noted in anatomical or electrophysiological tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinically viable approach to restoring visual function using optogenetic gene therapy. Yan, B., Viswanathan, S., Brodie, SE., et al.[2023]

The first-in-human phase 1/2 clinical trial of retinal gene therapy for X-linked retinitis pigmentosa (RP) involving 18 patients showed that the treatment was generally safe, with only mild steroid-responsive inflammation noted at higher doses.

Significant visual field improvements were observed in six patients starting from one month after treatment and lasting through the 6-month follow-up, indicating potential efficacy of the gene therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Cehajic-Kapetanovic, J., Xue, K., Martinez-Fernandez de la Camara, C., et al.[2023]

The study developed Span-polyarginine (SP-PA) nanoparticles for delivering the PRPF31 gene to treat autosomal dominant retinitis pigmentosa (adRP), showing effective gene transfer in a mouse model with a specific mutation.

Treatment with SP-PA nanoparticles resulted in significant improvements in visual acuity and retinal thickness in the affected mice, indicating potential efficacy for this gene therapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Span poly-L-arginine nanoparticles are efficient non-viral vectors for PRPF31 gene delivery: An approach of gene therapy to treat retinitis pigmentosa. Pensado, A., Diaz-Corrales, FJ., De la Cerda, B., et al.[2018]

The study assessed the safety of a gene therapy using a recombinant adeno-associated virus vector (rAAV2-CB-hRPE65) in 12 patients (8 adults and 4 children) with retinal degeneration due to RPE65 mutations, finding no serious treatment-related adverse events after 2 years of follow-up.

Improvements in visual function were observed in 9 out of 12 patients, with the most significant gains in younger patients who had better baseline visual acuity, indicating potential efficacy of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy. Weleber, RG., Pennesi, ME., Wilson, DJ., et al.[2017]

Gene therapy has shown potential in delivering transgenes to the retina effectively and safely, which could help slow or prevent blindness caused by retinitis pigmentosa (RP).

Recent advancements in understanding the molecular basis of RP, along with successful gene transfer experiments in animal models, suggest that gene therapy could be a viable treatment option in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for retinitis pigmentosa. Bennett, J.[2012]

References

1. United States pubmed.ncbi.nlm.nih.gov

Halting progressive neurodegeneration in advanced retinitis pigmentosa. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Success of Gene Therapy in Late-Stage Treatment. [2019]

3. Japan pubmed.ncbi.nlm.nih.gov

Long-term clinical course of 2 Japanese patients with PRPF31-related retinitis pigmentosa. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Disease progression of retinitis pigmentosa caused by PRPF31 variants in a Nordic population: a retrospective study with up to 36 years follow-up. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

A clinically viable approach to restoring visual function using optogenetic gene therapy. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Span poly-L-arginine nanoparticles are efficient non-viral vectors for PRPF31 gene delivery: An approach of gene therapy to treat retinitis pigmentosa. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Gene therapy for retinitis pigmentosa. [2012]