Trabodenoson found to prevent retinal ganglion cell death, the cause of vision loss in glaucoma patients, in preclinical animal model
LEXINGTON, MA, USA I May 30, 2014 I Inotek Pharmaceuticals Inc., a leader in the development of innovative products for the treatment of glaucoma, today announced the results from a preclinical study demonstrating the ability of trabodenoson, an adenosine A1 mimetic in development for glaucoma, to protect against the loss of retinal ganglion cells in an acute high-ocular-pressure animal model of glaucoma. Retinal ganglion cells are the part of the nervous system responsible for relaying the visual image from the eye to the brain, and their death is what causes the irreversible vision loss associated with glaucoma. The results of this study were presented this month at the 2014 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO).
This preclinical neuroprotection study was designed to compare the protective effects of trabodenoson and brimonidine in a rat model of ischemia-induced retinal ganglion cell (RGC) death. Trabodenoson was delivered as an eye drop at a clinically relevant dose. Results of the study showed that trabodenoson provided 100% protection against the thinning of the ganglion cell layer (p≤0.001 compared to vehicle-treated eyes).
“These data are both encouraging and consistent with the known effects of naturally occurring or endogenous adenosine in central nervous system tissue where it is well known to be neuroprotective”, said William McVicar, Ph.D., Inotek’s Chief Scientific Officer. “Adenosine’s protective effects have been attributed to its action at a specific receptor on cells – the adenosine A1 receptor – which is potently and selectively targeted by trabodenoson. Further, adenosine A1 receptors are found in retinal ganglion cells, providing a strong rationale for the drug’s ability to specifically protect this critical population of retinal cells.”
The study was completed in the laboratory of Leonard A. Levin, MD, PhD, at the University of Wisconsin in Madison. Dr. Levin, Chairman of the Department of Ophthalmology at McGill University in Montreal and a member of Inotek’s Scientific Advisory Board, commented, “These findings are very encouraging. Trabodenoson could have the potential to directly protect retinal ganglion cells, and thus slowing or preventing the optic nerve neuropathy that is the root cause of glaucomatous vision loss.”
About Trabodenoson for Glaucoma
Trabodenoson is an eye drop therapy in clinical development for the treatment of glaucoma, a leading cause of blindness globally. In a clinical Phase 2b trial, trabodenoson was found to be safe and well tolerated as a single agent, with intraocular pressure (IOP) lowering efficacy in the range of the prostaglandin analogs. Another Phase 2b clinical study of trabodenoson, in combination with the most widely-prescribed glaucoma drug, the prostaglandin analog latanoprost (LAT), is ongoing. Patients admitted to the trial must have elevated intraocular pressure (IOP) that remains uncontrolled despite ongoing treatment with latanoprost. The study will measure the additive or synergistic IOP-lowering effect of trabodenoson when combined with LAT, and will also evaluate the safety and tolerability of the combined treatment regimen. Top line data is expected in the 4th quarter of 2014.
When trabodenoson stimulates adenosine A1 receptors, fluid outflow is increased via the trabecular meshwork, the eye’s main drainage pathway, and the ocular pressure is reduced. This novel mechanism of action is significantly differentiated from currently approved products, as well as those in development.
Current products for glaucoma, such as prostaglandins, lower IOP by either reducing the inflow of fluid in the eye or by increasing its drainage through a secondary outflow pathway in the eye — the uveoscleral pathway. However, none of these drugs safely and effectively target the trabecular meshwork, the primary outflow pathway where the majority of aqueous fluid exits the eye. The trabecular meshwork comprises a pressure-sensitive mechanism through which healthy eyes maintain a normal, safe ocular pressure (IOP). As the eye ages and glaucoma advances, flow through the eye’s trabecular meshwork grows increasingly difficult. Trabodenoson has been shown to target an endogenous pathway that increase the natural metabolic activity of the trabecular meshwork tissue, by up-regulating proteases found in the eye. These proteases are responsible for clearing out hydrolyzed proteins, which block outflow, thus restoring the eye to a more normal, healthy state.
About Inotek
Inotek Pharmaceuticals is a privately held and funded biotechnology company focused on the discovery and development of innovative drugs to address serious diseases of the eye. Inotek scientists have identified a deep pipeline of drug candidates to ameliorate inflammation, ischemia-reperfusion injury, and oxidative stress, which are key targets for drugs to treat Glaucoma, Ocular Hypertension, Age-related Macular Degeneration and Retinal Neuropathies.
SOURCE: Inotek Pharmaceuticals
Post Views: 188
Trabodenoson found to prevent retinal ganglion cell death, the cause of vision loss in glaucoma patients, in preclinical animal model
LEXINGTON, MA, USA I May 30, 2014 I Inotek Pharmaceuticals Inc., a leader in the development of innovative products for the treatment of glaucoma, today announced the results from a preclinical study demonstrating the ability of trabodenoson, an adenosine A1 mimetic in development for glaucoma, to protect against the loss of retinal ganglion cells in an acute high-ocular-pressure animal model of glaucoma. Retinal ganglion cells are the part of the nervous system responsible for relaying the visual image from the eye to the brain, and their death is what causes the irreversible vision loss associated with glaucoma. The results of this study were presented this month at the 2014 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO).
This preclinical neuroprotection study was designed to compare the protective effects of trabodenoson and brimonidine in a rat model of ischemia-induced retinal ganglion cell (RGC) death. Trabodenoson was delivered as an eye drop at a clinically relevant dose. Results of the study showed that trabodenoson provided 100% protection against the thinning of the ganglion cell layer (p≤0.001 compared to vehicle-treated eyes).
“These data are both encouraging and consistent with the known effects of naturally occurring or endogenous adenosine in central nervous system tissue where it is well known to be neuroprotective”, said William McVicar, Ph.D., Inotek’s Chief Scientific Officer. “Adenosine’s protective effects have been attributed to its action at a specific receptor on cells – the adenosine A1 receptor – which is potently and selectively targeted by trabodenoson. Further, adenosine A1 receptors are found in retinal ganglion cells, providing a strong rationale for the drug’s ability to specifically protect this critical population of retinal cells.”
The study was completed in the laboratory of Leonard A. Levin, MD, PhD, at the University of Wisconsin in Madison. Dr. Levin, Chairman of the Department of Ophthalmology at McGill University in Montreal and a member of Inotek’s Scientific Advisory Board, commented, “These findings are very encouraging. Trabodenoson could have the potential to directly protect retinal ganglion cells, and thus slowing or preventing the optic nerve neuropathy that is the root cause of glaucomatous vision loss.”
About Trabodenoson for Glaucoma
Trabodenoson is an eye drop therapy in clinical development for the treatment of glaucoma, a leading cause of blindness globally. In a clinical Phase 2b trial, trabodenoson was found to be safe and well tolerated as a single agent, with intraocular pressure (IOP) lowering efficacy in the range of the prostaglandin analogs. Another Phase 2b clinical study of trabodenoson, in combination with the most widely-prescribed glaucoma drug, the prostaglandin analog latanoprost (LAT), is ongoing. Patients admitted to the trial must have elevated intraocular pressure (IOP) that remains uncontrolled despite ongoing treatment with latanoprost. The study will measure the additive or synergistic IOP-lowering effect of trabodenoson when combined with LAT, and will also evaluate the safety and tolerability of the combined treatment regimen. Top line data is expected in the 4th quarter of 2014.
When trabodenoson stimulates adenosine A1 receptors, fluid outflow is increased via the trabecular meshwork, the eye’s main drainage pathway, and the ocular pressure is reduced. This novel mechanism of action is significantly differentiated from currently approved products, as well as those in development.
Current products for glaucoma, such as prostaglandins, lower IOP by either reducing the inflow of fluid in the eye or by increasing its drainage through a secondary outflow pathway in the eye — the uveoscleral pathway. However, none of these drugs safely and effectively target the trabecular meshwork, the primary outflow pathway where the majority of aqueous fluid exits the eye. The trabecular meshwork comprises a pressure-sensitive mechanism through which healthy eyes maintain a normal, safe ocular pressure (IOP). As the eye ages and glaucoma advances, flow through the eye’s trabecular meshwork grows increasingly difficult. Trabodenoson has been shown to target an endogenous pathway that increase the natural metabolic activity of the trabecular meshwork tissue, by up-regulating proteases found in the eye. These proteases are responsible for clearing out hydrolyzed proteins, which block outflow, thus restoring the eye to a more normal, healthy state.
About Inotek
Inotek Pharmaceuticals is a privately held and funded biotechnology company focused on the discovery and development of innovative drugs to address serious diseases of the eye. Inotek scientists have identified a deep pipeline of drug candidates to ameliorate inflammation, ischemia-reperfusion injury, and oxidative stress, which are key targets for drugs to treat Glaucoma, Ocular Hypertension, Age-related Macular Degeneration and Retinal Neuropathies.
SOURCE: Inotek Pharmaceuticals
Post Views: 188
