Garuda - Garba Rujukan Digital

Safety and Efficacy of Subretinal AAV-CRISPR/Cas9 Gene Editing for Rhodopsin-Mutant Retinitis Pigmentosa: A Phase I/IIa Dose-Escalation Triall Khairiel Anwar; Sony Sanjaya; Rizky Ayu; Fachruddin Sani
Sriwijaya Journal of Ophthalmology Vol. 8 No. 2 (2025): Sriwijaya Journal of Ophthalmology
Publisher : Department of Opthalmology, Faculty of Medicine, Universitas Sriwijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/sjo.v8i2.137

Introduction: Autosomal dominant retinitis pigmentosa (adRP) from rhodopsin (RHO) mutations lacks an approved gene therapy. This Phase I/IIa trial evaluated subretinal AAV5-CRISPR/Cas9 for RHO-adRP. Methods: An open-label, 3+3 dose-escalation design with expansion at the recommended Phase II dose (RP2D) was used. Eighteen patients (18 study eyes; one eye per patient) received subretinal AAV5-CRISPR/Cas9 at low (1.5×1010 vg, n = 3), mid (5.0×1010 vg, n = 3), or high (1.5×1011 vg, n = 6) doses, plus an expansion cohort (n = 6) at RP2D, at a private hospital in Palembang, Indonesia. The primary endpoint was dose-limiting toxicities (DLTs); secondary endpoints were BCVA (LogMAR), SD-OCT ellipsoid zone (EZ) width, microperimetry, and ffERG. Results: No DLTs occurred. The high-dose cohort showed a BCVA improvement of −0.14 LogMAR (95% CI −0.22 to −0.06, p = 0.003; Cohen d = 1.82), an EZ width increase of +312 µm (95% CI +187 to +437, p < 0.001; d = 2.45), and a microperimetry gain of +3.8 dB (95% CI +2.1 to +5.5, p < 0.001; d = 1.94). Dose-response trends were significant (Jonckheere–Terpstra p-trend: BCVA 0.008, EZ 0.002). Conclusion: Subretinal AAV5-CRISPR/Cas9 demonstrated acceptable safety with dose-dependent structural and functional improvements at 12 months. Phase II/III trials are warranted.

Mobile Health Intervention to Improve Uptake and 12-Month Continuation of Long-Acting Reversible Contraception Among Urban Female Adolescents: A Multicenter Randomized Controlled Trial Rizky Ayu; Sana Ullah; Immanuel Simbolon
Sriwijaya Journal of Obstetrics and Gynecology Vol. 3 No. 2 (2025): Sriwijaya Journal of Obstetrics & Gynecology
Publisher : Phlox Institute: Indonesian Medical Research Organization

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59345/sjog.v3i2.283

Introduction: Adolescent pregnancy remains a major source of obstetric and psychosocial morbidity in densely populated Indonesian cities. Long-acting reversible contraception (LARC) offers first-line efficacy, yet adolescent uptake and continuation are constrained by misinformation and stigma. Mobile health (mHealth) may bridge this gap discreetly. We evaluated whether an interactive, encrypted mHealth platform improves LARC uptake and 12-month continuation versus standard care. Methods: We conducted a parallel, two-arm (1:1), open-label multicenter randomized controlled trial with blinded outcome assessment at two tertiary reproductive-health centers in Jakarta and Palembang, Indonesia. Sexually active women aged 15–21 years not desiring pregnancy within 12 months were block-randomized (stratified by center and parity). The platform delivered interactive education, private counselor chat, and automated reminders. Primary outcomes were LARC uptake at 1 month (intention-to-treat) and time-to-discontinuation over 12 months, analyzed with risk ratios (RR), Kaplan–Meier survival, Cox regression, and number needed to treat (NNT). Results: Of 390 adolescents screened, 364 were randomized (182 per arm). LARC uptake was 36.8% with mHealth versus 16.5% with standard care (RR 2.23, 95% CI 1.53–3.26; adjusted odds ratio 2.95, 95% CI 1.80–4.84; p<0.001). Absolute risk reduction was 20.3% (NNT 5). The 12-month continuation rate was 82.1% versus 56.7% (log-rank p=0.014), and Cox regression showed a 62% lower discontinuation hazard (adjusted hazard ratio 0.38, 95% CI 0.17–0.85; p=0.018). Conclusion: An encrypted, interactive mHealth intervention more than doubled LARC uptake and improved 12-month continuation among urban Indonesian adolescents, supporting integration of scalable, stigma-sensitive digital platforms into adolescent family-planning services.

Genetically Proxied Circulating C-Reactive Protein and Selected Cytokines in Relation to Register-Defined Sensorineural Hearing Loss: A Two-Sample Mendelian Randomization Study Rizky Ayu; Adolfo Rawlings; Aleisha Wulandari; Brenda Jaleel
Sriwijaya Journal of Otorhinolaryngology Vol. 3 No. 2 (2025): Sriwijaya Journal of Otorhinolaryngology
Publisher : Phlox Institute: Indonesian Medical Research Organization

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59345/sjorl.v3i2.308

Background: Circulating inflammatory biomarkers are associated with sensorineural hearing loss (SNHL), but observational studies cannot establish causality. Objective: To evaluate whether genetically proxied C-reactive protein (CRP) and eight cytokines are associated with SNHL. Methods: We used European-ancestry GWASs for CRP (N = 575,531) and eight cytokines (maximum N = 74,783), with FinnGen R13 outcomes of 48,388 SNHL cases and 432,132 controls; sudden idiopathic hearing loss (4,082 cases) was secondary. Variants were harmonized and pruned using 1000 Genomes Finnish linkage disequilibrium (r² < 0.001 within 10 Mb). Random-effects inverse-variance weighting or a Wald ratio was primary. Sensitivity analyses included MR-Egger, weighted median and mode, MR-RAPS, RadialMR, Steiger directionality, cis-only estimates, source-assay filters, and false-discovery-rate correction. Results: Of 301 unique exposure rsIDs, 279 were retrieved and 276 exposure rows passed harmonization. Finnish LD pruning left 238 CRP instruments. CRP was compatible with the null (OR per unit increase in ln[CRP mg/L], 1.005; 95% CI, 0.948–1.065; p = 0.868), consistent with weighted median, MR-Egger, weighted mode, and MR-RAPS estimates. No cytokine survived FDR correction (all q ≥ 0.393), source-assay filtering yielded no supported association, and secondary-outcome estimates were null. Steiger analyses favored the exposure-to-outcome direction. Conclusion: Results support no material effect of lifelong genetically proxied circulating CRP on register-defined SNHL. Cytokine evidence remains less definitive because instrument sets were small, predominantly trans acting, heterogeneous, and assay sensitive. The findings neither exclude acute or cochlea-specific inflammation nor evaluate corticosteroid effectiveness. Independent replication and cis-pQTL colocalization are required before therapeutic inference.

Safety and Efficacy of Subretinal AAV-CRISPR/Cas9 Gene Editing for Rhodopsin-Mutant Retinitis Pigmentosa: A Phase I/IIa Dose-Escalation Triall Khairiel Anwar; Sony Sanjaya; Rizky Ayu; Fachruddin Sani
Sriwijaya Journal of Ophthalmology Vol. 8 No. 2 (2025): Sriwijaya Journal of Ophthalmology
Publisher : Department of Ophthalmology, Faculty of Medicine, Universitas Sriwijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/sjo.v8i2.137

Introduction: Autosomal dominant retinitis pigmentosa (adRP) from rhodopsin (RHO) mutations lacks an approved gene therapy. This Phase I/IIa trial evaluated subretinal AAV5-CRISPR/Cas9 for RHO-adRP. Methods: An open-label, 3+3 dose-escalation design with expansion at the recommended Phase II dose (RP2D) was used. Eighteen patients (18 study eyes; one eye per patient) received subretinal AAV5-CRISPR/Cas9 at low (1.5×1010 vg, n = 3), mid (5.0×1010 vg, n = 3), or high (1.5×1011 vg, n = 6) doses, plus an expansion cohort (n = 6) at RP2D, at a private hospital in Palembang, Indonesia. The primary endpoint was dose-limiting toxicities (DLTs); secondary endpoints were BCVA (LogMAR), SD-OCT ellipsoid zone (EZ) width, microperimetry, and ffERG. Results: No DLTs occurred. The high-dose cohort showed a BCVA improvement of −0.14 LogMAR (95% CI −0.22 to −0.06, p = 0.003; Cohen d = 1.82), an EZ width increase of +312 µm (95% CI +187 to +437, p < 0.001; d = 2.45), and a microperimetry gain of +3.8 dB (95% CI +2.1 to +5.5, p < 0.001; d = 1.94). Dose-response trends were significant (Jonckheere–Terpstra p-trend: BCVA 0.008, EZ 0.002). Conclusion: Subretinal AAV5-CRISPR/Cas9 demonstrated acceptable safety with dose-dependent structural and functional improvements at 12 months. Phase II/III trials are warranted.

Title

Found 4 Documents
Search

Abstract

Abstract

Abstract

Abstract

Title Search

Found 4 Documents Search

Abstract

Abstract

Abstract

Abstract

Title

Found 4 Documents
Search