This technology is a generally applicable gene therapy approach that restores metabolic dysregulation and treats retinal degenerative diseases regardless of genetic variation.
Unmet Need: Comprehensive therapeutic for patients with retinal degeneration
Retinitis pigmentosa (RP) is a retinal degenerative disease that leads to loss of photoreceptors and irreversible blindness. RP is a genetically diverse disorder, such that gene-specific therapies are potentially effective in only a small fraction of patients with RP, thus limiting the use of conventional gene-specific therapeutic approaches. While metabolic imbalances and oxidative stress are thought to contribute to disease progression, there are currently no effective, broad-based treatments available for patients with genetic retinal degenerative disorders, including RP, glaucoma, autosomal dominant optic atrophy (ADOA), and age-related macular degeneration.
The Technology: Gene therapy for targeting metabolic imbalance and treatment of retinal degeneration
This technology is a gene therapy for treating retinal degenerative diseases, regardless of genetic variation, by restoring metabolic imbalances that lead to photoreceptor death and vision loss. Adeno-associated viral (AAV) vectors are used to deliver a transgene encoding PGC1α or NRF2 to retinal pigment epithelial (RPE) cells or retinal ganglion cells (RGC) and/or to deliver nucleic acid inhibitors of HIF or KEAP1 to RPE cells, including for example antisense oligonucleotides, siRNA, or guide RNAs and Cas nucleases. By targeting metabolic dysregulation and oxidative stress, this technology stalls degeneration in RPE and RG cells in a non-gene-specific manner.
Applications:
- Gene therapy for retinitis pigmentosa, glaucoma, autosomal dominant optic atrophy (ADOA), and age-related macular degeneration
- Gene therapy for other neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s, Amyotrophic lateral sclerosis (ALS), and Lewy body dementia, that would benefit from upregulating anabolism and downregulating catabolism to promote neuronal survival
- Gene therapy for eye-related degenerative diseases
- Gene therapy for metabolic dysregulation disorders
- Research tool for metabolic regulation in the retina
- Tool for studying antioxidant overexpression
Advantages:
- Treats retinal degenerative diseases regardless of genetic background
- Stalls retinal degeneration
- Targets metabolic dysregulation and oxidative stress
- Restores the balance between oxidative phosphorylation and anabolism in the eye
Lead Inventor:
Stephen Tsang, M.D., Ph.D.
Patent Information:
Patent Pending (US20230070477)
Related Publications:
Zhang L, Du J, Justus S, Hsu CW, Bonet-Ponce L, Wu WH, Tsai YT, Wu WP, Jia Y, Duong JK, Mahajan VB, Lin CS, Wang S, Hurley JB, Tsang SH. “Reprogramming metabolism by targeting sirtuin 6 attenuates retinal degeneration.” J Clin Invest. 2016 Dec 1;126(12):4659-4673.
Zhang L, Justus S, Xu Y, Pluchenik T, Hsu CW, Yang J, Duong JK, Lin CS, Jia Y, Bassuk AG, Mahajan VB, Tsang SH. “Reprogramming towards anabolism impedes degeneration in a preclinical model of retinitis pigmentosa.” Hum Mol Genet. 2016 Oct 1;25(19):4244-4255.
Tech Ventures Reference:
IR CU18340, CU20065, CU20389
