ArticlePloS one2017
First-in-human phase I study of ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2), in subjects with open-angle glaucoma undergoing glaucoma filtration surgery.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
- Small Nucleic Acid Therapeutics for Ocular Diseases: Progress, Challenges, and Future Perspectives.Pharmaceutics · 2026Review
- Meta-analysis of adverse events in clinical studies with antisense oligonucleotide therapies.Molecular therapy. Nucleic acids · 2026Review
- TGF-beta inhibitors in cancer therapy: a review of the TGF-beta signal transduction pathway and current developments.EXCLI journal · 2026Review
- Targeting the Eye: RNA-Based Therapies, Interferences, and Delivery Strategies.Pharmaceutics · 2025Review
- Tackling visual impairment: emerging avenues in ophthalmology.Frontiers in medicine · 2025Review
- Recent advances in therapeutic use of transforming growth factor-beta inhibitors in cancer and fibrosis.Frontiers in oncology · 2025Review
- Exploring TGF-β Signaling in Cancer Progression: Prospects and Therapeutic Strategies.OncoTargets and therapy · 2025Review
- Antisense Oligonucleotide STK-002 Increases OPA1 in Retina and Improves Mitochondrial Function in Autosomal Dominant Optic Atrophy Cells.Nucleic acid therapeutics · 2024Article
- Introduction of sugar-modified nucleotides into CpG-containing antisense oligonucleotides inhibits TLR9 activation.Scientific reports · 2024Article
- Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Elevated Intraocular Pressure and Glaucomatous Optic Neuropathy: Genes to Disease Mechanisms, Therapeutic Drugs, and Gene Therapies.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Recently Approved Drugs for Lowering and Controlling Intraocular Pressure to Reduce Vision Loss in Ocular Hypertensive and Glaucoma Patients.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Nanotechnology Lighting the Way for Gene Therapy in Ophthalmopathy: From Opportunities toward Applications.Molecules (Basel, Switzerland) · 2023Review
- Transforming growth factor-β signaling: from tumor microenvironment to anticancer therapy.Exploration of targeted anti-tumor therapy · 2023Review
- TGF-beta signal transduction: biology, function and therapy for diseases.Molecular biomedicine · 2022Review
- Selective Activation of the Wnt-Signaling Pathway as a Novel Therapy for the Treatment of Diabetic Retinopathy and Other Retinal Vascular Diseases.Pharmaceutics · 2022Review
- Review
- Remodeling of the Lamina Cribrosa: Mechanisms and Potential Therapeutic Approaches for Glaucoma.International journal of molecular sciences · 2022Review
- Review
- Review
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo evaluate the safety and tolerability of intravitreal ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2), in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy (TE; glaucoma filtration surgery).
methodsIn this prospective phase I trial glaucoma patients scheduled for TE with mitomycin C (MMC) received a single intravitreal injection of ISTH0036 at the end of surgery in escalating total doses of 6.75 μg, 22.5 μg, 67.5 μg or 225 μg, resulting in calculated intraocular ISTH0036 concentrations in the vitreous humor of approximately 0.3 μM, 1 μM, 3 μM or 10 μM after injection, respectively. Outcomes assessed included: type and frequency of adverse events (AEs), intraocular pressure (IOP), numbers of interventions post trabeculectomy, bleb survival, visual acuity, visual field, electroretinogram (ERG), slit lamp biomicroscopy and optic disc assessment.
resultsIn total, 12 patients were treated in the 4 dose groups. Main ocular AEs observed were corneal erosion, corneal epithelium defect, or too high or too low IOP, among others. No AE was reported to be related to ISTH0036. All other safety-related analyses did not reveal any toxicities of concern, either. The mean medicated preoperative IOP at decision time-point for surgery was 27.3 mmHg +/- 12.6 mmHg (SD). Mean IOP (±SD) for dose levels 1, 2, 3, and 4 were at Day 43 9.8 mmHg ± 1.0 mmHg, 11.3 mmHg ± 6.7 mmHg, 5.5 mmHg ± 3.0 mmHg and 7.5 mmHg ± 2.3 mmHg SD; and at Day 85 9.7 mmHg ± 3.3 mmHg, 14.2 mmHg ± 6.5 mmHg, 5.8 mmHg ± 1.8 mmHg and 7.8 mmHg ± 0.6 mmHg, respectively. In contrast to IOP values for dose levels 1 and 2, IOP values for dose levels 3 and 4 persistently remained below 10 mmHg throughout the observation period.
conclusionThis first-in-human trial demonstrates that intravitreal injection of ISTH0036 at the end of TE is safe. Regarding IOP control, single-dose ISTH0036 administration of 67.5 μg or 225 μg at the time of TE resulted in IOP values persistently < 10 mmHg over the three month postoperative observation period.
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