Gene Therapy for Retinitis Pigmentosa
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Bionic Sight LLC
Disqualifiers: Prior AAV therapy, Nystagmus
No Placebo Group
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.
12345Is 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.
15678What 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.
12569Eligibility 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.
Trial 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
Participant Groups
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.
4Treatment groups
Experimental Treatment
Group I: Cohort 4Experimental Treatment1 Intervention
BS01 Cohort4 dose
Group II: Cohort 3Experimental Treatment1 Intervention
BS01 Cohort 3 dose
Group III: Cohort 2Experimental Treatment1 Intervention
BS01 Cohort 2 dose
Group IV: Cohort 1Experimental Treatment1 Intervention
BSO1 Cohort 1 dose
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
OCLINew York, NY
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Who Is Running the Clinical Trial?
Bionic Sight LLCLead Sponsor
References
Halting progressive neurodegeneration in advanced retinitis pigmentosa. [2018]Hereditary retinal degenerative diseases, such as retinitis pigmentosa (RP), are characterized by the progressive loss of rod photoreceptors followed by loss of cones. While retinal gene therapy clinical trials demonstrated temporary improvement in visual function, this approach has yet to achieve sustained functional and anatomical rescue after disease onset in patients. The lack of sustained benefit could be due to insufficient transduction efficiency of viral vectors ("too little") and/or because the disease is too advanced ("too late") at the time therapy is initiated. Here, we tested the latter hypothesis and developed a mouse RP model that permits restoration of the mutant gene in all diseased photoreceptor cells, thereby ensuring sufficient transduction efficiency. We then treated mice at early, mid, or late disease stages. At all 3 time points, degeneration was halted and function was rescued for at least 1 year. Not only do our results demonstrate that gene therapy effectively preserves function after the onset of degeneration, our study also demonstrates that there is a broad therapeutic time window. Moreover, these results suggest that RP patients are treatable, despite most being diagnosed after substantial photoreceptor loss, and that gene therapy research must focus on improving transduction efficiency to maximize clinical impact.
Success of Gene Therapy in Late-Stage Treatment. [2019]Retinal gene therapy has yet to achieve sustained rescue after disease onset - perhaps because transduction efficiency is insufficient ("too little") and/or the disease is too advanced ("too late") in humans. To test the latter hypothesis, we used a mouse model for retinitis pigmentosa (RP) that allowed us to restore the mutant gene in all diseased rod photoreceptor cells, thereby generating optimally treated retinas. We then treated mice at an advanced disease stage and analyzed the rescue. We showed stable, sustained rescue of photoreceptor structure and function for at least 1 year, demonstrating gene therapy efficacy after onset of degeneration. The results suggest that RP patients are treatable, even when the therapy is administered at late disease stages.
Long-term clinical course of 2 Japanese patients with PRPF31-related retinitis pigmentosa. [2018]To assess the long-term clinical course of 2 patients with PRPF31-related retinitis pigmentosa (RP).
Disease progression of retinitis pigmentosa caused by PRPF31 variants in a Nordic population: a retrospective study with up to 36 years follow-up. [2023]To investigate the natural history of PRPF31-related retinitis pigmentosa (RP11).
A clinically viable approach to restoring visual function using optogenetic gene therapy. [2023]Optogenetic gene therapies offer a promising strategy for restoring vision to patients with retinal degenerative diseases, such as retinitis pigmentosa (RP). Several clinical trials have begun in this area using different vectors and optogenetic proteins (Clinical Identifiers: NCT02556736, NCT03326336, NCT04945772, and NCT04278131). Here we present preclinical efficacy and safety data for the NCT04278131 trial, which uses an AAV2 vector and Chronos as the optogenetic protein. Efficacy was assessed in mice in a dose-dependent manner using electroretinograms (ERGs). Safety was assessed in rats, nonhuman primates, and mice, using several tests, including immunohistochemical analyses and cell counts (rats), electroretinograms (nonhuman primates), and ocular toxicology assays (mice). The results showed that Chronos-expressing vectors were efficacious over a broad range of vector doses and stimulating light intensities, and were well tolerated: no test article-related findings were observed in the anatomical and electrophysiological assays performed.
Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. [2023]Retinal gene therapy has shown great promise in treating retinitis pigmentosa (RP), a primary photoreceptor degeneration that leads to severe sight loss in young people. In the present study, we report the first-in-human phase 1/2, dose-escalation clinical trial for X-linked RP caused by mutations in the RP GTPase regulator (RPGR) gene in 18 patients over up to 6 months of follow-up (https://clinicaltrials.gov/: NCT03116113). The primary outcome of the study was safety, and secondary outcomes included visual acuity, microperimetry and central retinal thickness. Apart from steroid-responsive subretinal inflammation in patients at the higher doses, there were no notable safety concerns after subretinal delivery of an adeno-associated viral vector encoding codon-optimized human RPGR (AAV8-coRPGR), meeting the pre-specified primary endpoint. Visual field improvements beginning at 1 month and maintained to the last point of follow-up were observed in six patients.
Span poly-L-arginine nanoparticles are efficient non-viral vectors for PRPF31 gene delivery: An approach of gene therapy to treat retinitis pigmentosa. [2018]Retinitis pigmentosa (RP) is the most common cause of inherited blindness in adults. Mutations in the PRPF31 gene produce autosomal dominant RP (adRP). To date there are no effective treatments for this disease. The purpose of this study was to design an efficient non-viral vector for human PRPF31 gene delivery as an approach to treat this form of adRP. Span based nanoparticles were developed to mediate gene transfer in the subretinal space of a mouse model of adRP carrying a point mutation (A216P) in the Prpf31 gene. Funduscopic examination, electroretinogram, optomotor test and optical coherence tomography were conducted to further in vivo evaluate the safety and efficacy of the nanosystems developed. Span-polyarginine (SP-PA) nanoparticles were able to efficiently transfect the GFP and PRPF31 plasmid in mice retinas. Statistically significant improvement in visual acuity and retinal thickness were found in Prpf31A216P/+ mice treated with the SP-PA-PRPF31 nanomedicine.
Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy. [2017]To provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations.
Gene therapy for retinitis pigmentosa. [2012]Retinitis pigmentosa (RP) is a group of retinal degenerative diseases in which there is a slow and progressive loss of photoreceptors. There is no cure for RP and photoreceptor loss leads ultimately to blindness. There has been tremendous progress in the last decade in delineating the molecular basis of RP. Simultaneously, gene transfer experiments have demonstrated that it is possible to deliver transgenes to the retina in vivo in a stable and efficient fashion with minimal toxicity. Proof-of-principle for gene therapy for RP has been established in a number of different animal models. While much more progress needs to be made before moving from the laboratory to the clinic, gene therapy now holds much promise for slowing or even preventing blindness due to RP.