Gene Therapy for Retinitis Pigmentosa: Current Challenges and New Progress

Biomolecules, Год журнала: 2024, Номер 14(8), С. 903 - 903

Опубликована: Июль 25, 2024

Retinitis pigmentosa (RP) poses a significant threat to eye health worldwide, with prevalence rates of 1 in 5000 worldwide. This genetically diverse retinopathy is characterized by the loss photoreceptor cells and atrophy retinal pigment epithelium. Despite involvement more than 3000 mutations across approximately 90 genes its onset, finding an effective treatment has been challenging for considerable time. However, advancements scientific research, especially gene therapy, are significantly expanding options this most prevalent inherited disease, discovery new compounds, gene-editing techniques, loci offering hope treatments. Gene promising technology, utilizes viral or non-viral vectors correct genetic defects either replacing silencing disease-causing genes, potentially leading complete recovery. In review, we primarily focus on latest applications editing research RP. We delve into associated RP discuss genome-editing strategies currently employed various mutations.

Язык: Английский

---

Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) Gene Therapy: Safety and Efficacy in RPGR-associated X-linked Retinitis Pigmentosa

American Journal of Ophthalmology, Год журнала: 2024, Номер 267, С. 122 - 134

Опубликована: Июнь 12, 2024

To assess the safety and efficacy of AAV5-hRKp.RPGR in participants with retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked (XLRP).

Язык: Английский

---

Retina-on-Chip: Engineering Functional in vitro Models of the Human Retina using Organ-on-Chip Technology

Lab on a Chip, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

The retina is a complex and highly metabolic tissue in the back of eye essential for human vision. In this review, we provide insights field retina-on-chip based on current research.

Язык: Английский

---

Pre-Clinical and Clinical Advances in Gene Therapy of X-Linked Retinitis Pigmentosa: Hope on the Horizon

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(3), С. 898 - 898

Опубликована: Янв. 29, 2025

X-linked retinitis pigmentosa (XLRP) is a severe inherited retinal degenerative disease characterized by progressive loss of photoreceptors and pigment epithelium, leading to blindness. Predominantly affecting males due mutations in the RPGR gene, XLRP currently lacks effective treatments beyond supportive care. Gene therapy has emerged as promising approach restore photoreceptor function delivering functional copies gene. Recent clinical trials using AAV vectors, such AAV5-RPGR AGTC-501, have demonstrated encouraging results, including improvements sensitivity visual function. While early successes like LUXTURNA set precedent for gene diseases, adapting these strategies presents unique challenges complexity need efficient targeting. Advances vector design, use optimized serotypes with enhanced tropism specific promoters, significantly improved delivery. Despite setbacks some studies, ongoing research continue refine therapies, offering hope patients affected XLRP. This review explores etiology pathophysiology XLRP, evaluates current treatment challenges, highlights recent advances therapy, discusses future perspectives bringing therapies into practice.

Язык: Английский

---

CASE REPORTS: A previously unreported RPGR gene variant in a female patient with X-linked retinitis pigmentosa

Digital Journal of Ophthalmology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

We present the case of a 40-year-old woman with history high myopia and nyctalopia. Her best-corrected visual acuity was 20/80 in right eye 20/100 left eye. Fundus examination revealed generalized vascular attenuation, optic nerve pallor, bone spicule pigmentation. autofluorescence both eyes showed Robson-Holder ring macula multiple hypoautofluorescent lesions peripheral retina. Macular optical coherence tomography scans thinning retinal layers, atrophy outer layers. 10-2 fields small island central vision eyes, full field electroretinogram absence scotopic photopic responses. Genetic studies documented rare variant RPGR gene (c.1991C>G p.(Ser664*)). Findings compatible retinitis pigmentosa our patient suggests that this mutation is pathogenic. Further study required to confirm hypothesis.

Язык: Английский

---

Organoids – the future of pre-clinical development of AAV gene therapy for CNS disorders

Gene Therapy, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

Abstract Advancements in our understanding of genetic disease and adeno-associated virus has prompted great excitement into the field AAV-mediated gene therapy, particularly for diseases central nervous system, including retinal disorders. Despite significant progress, exemplified by approval therapies such as Luxturna® Zolgensma®, a substantial number remain pre-clinical or early clinical stages, with many failing to advance later phases. Whilst use animal models test safety delivery route efficacy AAV treatments is imperative, differences tissue structure physiology between humans restricted precise modelling therapy development CNS Alongside FDA push non-animal alternative models, researchers are increasingly turning human-based stem cell-derived organoids, which can offer more accurate representation human cellular microenvironments niches. As such, this review explores advantages limitations brain organoids disease, primary focus on their utility identifying novel capsids, cell-specific promoters, role recent studies.

Язык: Английский

---

Retinal Organoids: Innovative Tools for Understanding Retinal Degeneration

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3263 - 3263

Опубликована: Апрель 1, 2025

Retinal degenerative diseases (RDDs) comprise diverse genetic and phenotypic conditions that cause progressive retinal dysfunction cell loss, leading to vision impairment or blindness. Most RDDs lack appropriate animal models for their study, which affects understanding disease mechanisms delays the progress of new treatment development. Recent advances in stem engineering, omics, organoid technology are facilitating research into there no previously existing models. The development organoids produced from human cells has impacted study as well vitro diseases, opening possibilities applications regenerative medicine, drug discovery, precision medicine. In this review, we recapitulate RDD, mentioning some main pathways underlying neurodegeneration can be studied these models, limitations future challenges rapidly advancing field.

Язык: Английский

---

Gene Therapies in Clinical Development to Treat Retinal Disorders

Molecular Diagnosis & Therapy, Год журнала: 2024, Номер 28(5), С. 575 - 591

Опубликована: Июль 2, 2024

Gene therapies have emerged as promising treatments in clinical development for various retinal disorders, offering hope to patients with inherited degenerative eye conditions. Several gene already shown remarkable success trials, significant improvements observed visual acuity and the preservation of function. A multitude now been delivered safely human trials a wide range disorders but there are some gaps reported trial data. Some most exciting treatment options not under peer review information is only available press release form. Whilst many appear good outcomes safety, others failed meet primary endpoints therefore proceeded phase III. Despite this, such enabled researchers learn how best assess monitor patient outcomes, which will guide future greater success. In this review, we consider recent ongoing variety potential therapy discuss positive negative issues related these trials. We following well risks investigation. As continue advance through rigorous testing regulatory approval processes, they hold revolutionise landscape disorder treatments, providing renewed vision enhancing quality life countless individuals worldwide.

Язык: Английский

---

Inherited Retinal Diseases and Retinal Organoids as Preclinical Cell Models for Inherited Retinal Disease Research

Genes, Год журнала: 2024, Номер 15(6), С. 705 - 705

Опубликована: Май 28, 2024

Inherited retinal diseases (IRDs) are a large group of genetically and clinically diverse blinding eye conditions that result in progressive irreversible photoreceptor degeneration vision loss. To date, no cures have been found, although strides toward treatments for specific IRDs made recent years. accelerate treatment discovery, organoids provide an ideal human IRD model. This review aims to give background on the development importance human-based vitro study retina retinogenesis pathologies. From there, we explore pathologies context current landscape discovery. We discuss usefulness this (as patient-derived cell model IRDs) precisely understand pathogenesis potential mechanisms behind IRD-causing variant interest. Finally, promise discovery IRDs, now future.

Язык: Английский

---

A Comparative Analysis of Models for AAV-Mediated Gene Therapy for Inherited Retinal Diseases

Cells, Год журнала: 2024, Номер 13(20), С. 1706 - 1706

Опубликована: Окт. 15, 2024

Inherited retinal diseases (IRDs) represent a diverse group of genetic disorders leading to progressive degeneration the retina due mutations in over 280 genes. This review focuses on various methodologies for preclinical characterization and evaluation adeno-associated virus (AAV)-mediated gene therapy as potential treatment option IRDs, particularly focusing therapies targeting mutations, such those RPE65 FAM161A AAV vectors, AAV2 AAV5, have been utilized deliver therapeutic genes, showing promise preserving vision enhancing photoreceptor function animal models. Despite their advantages—including high production efficiency, low pathogenicity, minimal immunogenicity—AAV-mediated face limitations immune responses beyond retina, vector size constraints, challenges large-scale manufacturing. systematically compares different experimental models used investigate AAV-mediated therapies, mouse models, human explants (HREs), induced pluripotent stem cell (iPSC)-derived organoids. Mouse are advantageous manipulation detailed investigations disease mechanisms; however, anatomical differences between mice humans may limit translational applicability results. HREs offer valuable insights into pathophysiology but tissue degradation lack systemic physiological effects. Retinal organoids, other hand, provide robust platform that closely mimics development, thereby enabling more comprehensive studies mechanisms strategies, including AAV-based interventions. Specific outcomes targeted these include preservation functional improvements retinas damaged by mutations. highlights strengths weaknesses each model advocates combined use developing IRDs. As research advances, optimizing design delivery methods will be critical efficacy improving clinical patients with

Язык: Английский

---