Prostaglandin-based rAAV-mediated glaucoma gene therapy in Brown Norway rats

Ertel, Kristina J.; Nettesheim, Emily R.; Reid, C.; Li, Nathan W.; Marcoe, Gavin J.; Lipinski, Daniel M.

doi:10.1038/s42003-022-04134-w

Cited by 9 publications

(4 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The combined delivery resulted in sustained reduction of IOP in a normotensive large animal (cat). More recently, using newer AAV vector technology, another group confirmed the IOP-lowering capacity of these genes in rats [27 ▪▪ ]. These investigators targeted the cornea endothelium, iris and ciliary body (not the trabecular meshwork), to produce the enzymes and secret them into the anterior chamber.…”

Section: Gene Therapies To Reduce Intraocular Pressurementioning

confidence: 99%

Genes as drugs for glaucoma: latest advances

Borrás,

Stepankoff,

Danias

2023

Current Opinion in Ophthalmology

View full text Add to dashboard Cite

Purpose of review To provide the latest advances on the future use of gene therapy for the treatment of glaucoma. Recent findings In preclinical studies, a number of genes have been shown to be able to reduce elevated intraocular pressure (IOP), and to exert neuroprotection of the retinal ganglion cells. These genes target various mechanisms of action and include among others: MMP3, PLAT, IκB, GLIS, SIRT, Tie-2, AQP1. Some of these as well as some previously identified genes (MMP3, PLAT, BDNF, C3, TGFβ, MYOC, ANGPTL7) are starting to move onto drug development. At the same time, progress has been made in the methods to deliver and control gene therapeutics (advances in these areas are not covered in this review). Summary While preclinical efforts continue in several laboratories, an increasing number of start-up and large pharmaceutical companies are working on developing gene therapeutics for glaucoma (Sylentis, Quetera/Astellas, Exhaura, Ikarovec, Genentech, Regeneron, Isarna, Diorasis Therapeutics). Despite the presence of generic medications to treat glaucoma, given the size of the potential world-wide market (∼$7B), it is likely that the number of companies developing glaucoma gene therapies will increase further in the near future.

show abstract

Section: Gene Therapies To Reduce Intraocular Pressurementioning

confidence: 99%

Genes as drugs for glaucoma: latest advances

Borrás,

Stepankoff,

Danias

2023

Current Opinion in Ophthalmology

View full text Add to dashboard Cite

show abstract

“…Modifying gene expression within the TM can facilitate increased aqueous humor outflow and sustained IOP reduction. Multiple studies have achieved IOP reduction for up to 12 months using siRNA and viral vector mediated gene therapy targeting prostaglandin synthesis enzymes at the TM in animal models [9,10,11 ▪ ,12]. Recently, Chern et al demonstrated a reduction in IOP in normotensive rats over a 12-month period using an AAV vector which increased biosynthesis of prostaglandin F2alpha [11 ▪ ].…”

Section: Gene Therapymentioning

confidence: 99%

“…Multiple studies have achieved IOP reduction for up to 12 months using siRNA and viral vector mediated gene therapy targeting prostaglandin synthesis enzymes at the TM in animal models [9,10,11 ▪ ,12]. Recently, Chern et al demonstrated a reduction in IOP in normotensive rats over a 12-month period using an AAV vector which increased biosynthesis of prostaglandin F2alpha [11 ▪ ]. Further, O’Callaghan et al demonstrated that AAV mediated expression of matrix metalloproteinaise-3 could increase aqueous humor outflow in murine glaucoma models, nonhuman primates, and donor human eyes [13 ▪▪ ].…”

Section: Gene Therapymentioning

confidence: 99%

Future directions of glaucoma treatment: emerging gene, neuroprotection, nanomedicine, stem cell, and vascular therapies

Ciociola,

Fernandez,

Kaufmann

et al. 2023

Current Opinion in Ophthalmology

View full text Add to dashboard Cite

Purpose of review The aim of this article is to summarize current research on novel gene, stem cell, neuroprotective, nanomedicine, and vascular therapies for glaucoma. Recent findings Gene therapy using viral vectors and siRNA have been shown to reduce intraocular pressure by altering outflow and production of aqueous humor, to reduce postsurgical fibrosis with few adverse effects, and to increase retinal ganglion cell (RGC) survival in animal studies. Stem cells may treat glaucoma by replacing or stimulating proliferation of trabecular meshwork cells, thus restoring outflow facility. Stem cells can also serve a neuroprotective effect by differentiating into RGCs or preventing RGC loss via secretion of growth factors. Other developing neuroprotective glaucoma treatments which can prevent RGC death include nicotinamide, the NT-501 implant which secretes ciliary neurotrophic factor, and a Fas-L inhibitor which are now being tested in clinical trials. Recent studies on vascular therapy for glaucoma have focused on the ability of Rho Kinase inhibitors and dronabinol to increase ocular blood flow. Summary Many novel stem cell, gene, neuroprotective, nanomedicine, and vascular therapies have shown promise in preclinical studies, but further clinical trials are needed to demonstrate safety and efficacy in human glaucomatous eyes. Although likely many years off, future glaucoma therapy may take a multifaceted approach.

show abstract

“…Therapy was well tolerated at low and medium doses, with no major adverse effects on the anterior chamber. Success in human trials could be an alternative to current treatment strategies, leading to a reduction in intraocular pressure without the need to follow a daily treatment regimen [20]. Matrix metalloproteinases (MMPs) contribute to maintaining the homeostasis of the aqueous outflow through their ability to remodel the extracellular matrix, which has a direct effect on the resistance of the aqueous flow and intraocular pressure.…”

Section: Potential Gene Therapy Strategies In Glaucomamentioning

confidence: 99%

Glaucoma – new possibilities, new research

Szumny

Mulak

2023

Ophthatherapy

View full text Add to dashboard Cite

Research efforts to develop effective and safe antiglaucoma drugs have been ongoing for many years. The cornerstone of treatment is still baroprotection, as this is virtually the only method available to protect the optic nerve and slow glaucoma progression, which can be easily controlled by an ophthalmologist. Research is also being conducted in the direction of neuroprotection, where new compounds are being evaluated, as well as those that have been used for years as adjunctive treatments. The greatest hope lies in gene therapy, which still has many problems to be solved, but it is the only one that offers hope for the patient’s complete recovery.

show abstract

Prostaglandin-based rAAV-mediated glaucoma gene therapy in Brown Norway rats

Cited by 9 publications

References 90 publications

Genes as drugs for glaucoma: latest advances

Genes as drugs for glaucoma: latest advances

Future directions of glaucoma treatment: emerging gene, neuroprotection, nanomedicine, stem cell, and vascular therapies

Glaucoma – new possibilities, new research

Contact Info

Product

Resources

About