Related Experiment Video
Updated: May 26, 2025
06:48
Limbal Approach-Subretinal Injection of Viral Vectors for Gene Therapy in Mice Retinal Pigment Epithelium
Published on: August 7, 2015
21.1K
Gene therapy in children with AIPL1-associated severe retinal dystrophy: an open-label, first-in-human interventional
Michel Michaelides1, Yannik Laich2, Sui Chien Wong3
1NIHR Moorfields Biomedical Research Centre, London, UK; UCL Institute of Ophthalmology, University College London, London, UK.
Lancet (London, England)
|February 22, 2025
Summary
Gene therapy for AIPL1-related retinal dystrophy significantly improved vision and preserved retinal structure in young children. Early intervention with subretinal AIPL1 gene supplementation showed promising safety and efficacy outcomes.
Area of Science:
- Ophthalmology and genetics
- Gene therapy for inherited retinal diseases
- Molecular and cellular biology of photoreceptor function
Background:
- AIPL1 gene mutations cause severe, early-onset retinal dystrophy leading to rapid vision loss.
- Current treatments are limited, necessitating exploration of novel therapeutic strategies.
- Gene supplementation therapy offers a potential approach to restore AIPL1 function.
Purpose of the Study:
- To evaluate the safety and efficacy of early gene supplementation therapy in children with AIPL1-related retinal dystrophy.
- To assess the impact of subretinal delivery of rAAV8.hRKp.AIPL1 on visual function and retinal structure.
Main Methods:
- A non-randomized, single-arm clinical study involving four children with AIPL1 mutations.
- Subretinal injection of a recombinant adeno-associated viral vector (rAAV8.hRKp.AIPL1) into one eye.
- Outcome measures included visual acuity, functional vision, visual evoked potentials, retinal structure (OCT, fundus imaging), and safety assessments.
Main Results:
- Significant improvement in visual acuity in treated eyes (mean 0.9 logMAR) compared to pre-intervention levels (2.7 logMAR).
- Untreated eyes showed unmeasurable visual acuity at follow-up, highlighting the treatment effect.
- Enhanced visual cortex activity and better preservation of outer retinal structure and thickness in treated eyes; one case of cystoid macular edema noted.
Conclusions:
- Subretinal administration of rAAV8.hRKp.AIPL1 gene therapy demonstrated substantial benefits in young children with AIPL1-related retinal dystrophy.
- The therapy improved visual acuity and functional vision, offering protection against retinal degeneration.
- Early intervention with this gene therapy appears safe and effective, with no serious adverse effects reported beyond transient inflammation.
Related Concept Videos
01:22iPS Cell Differentiation
2.6K
The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
2.6K
00:59Gene Therapy
25.1K
Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...
25.1K