Summary: ST266 produces an anti-inflammatory effect and can help preserve cells in the optic nerve, a new study reports.
Source: University of Pennsylvania.
A new therapeutic agent tested in a mouse model of multiple sclerosis (MS) produced anti-inflammatory activity and prevented loss of cells in the optic nerve, according to a new study by researchers in the Perelman School of Medicine at the University of Pennsylvania, with Pittsburgh-based Noveome Biotherapeutics. The research was conducted in the laboratory of Kenneth Shindler, MD, PhD, an associate professor of Ophthalmology and Neurology, and published in Scientific Reports.
The team demonstrated the therapeutic potential of the agent, called ST266, for treating optic neuritis, inflammation that damages the optic nerve and is a common presenting feature of MS. About half of patients diagnosed with MS experience optic neuritis, which can cause mild to moderate permanent loss of vision, but rarely complete blindness. ST266 is a solution of molecules that stimulate paracrine signaling. This is one way in which cells “talk” to each other: One cell produces a chemical signal that induces changes in nearby cells.
“In this case, the idea is that the many factors in ST266 not only bind to cell receptors and cause changes within the cells they bind to, but those cells then alter their own secretions and provide additional signals to other neighboring cells, thus propagating an effect from a relatively small amount of protein present in the therapy itself,” Shindler said. “To the best of our knowledge, this study demonstrates, for the first time, the ability to treat the optic nerve via the intranasal route of administration.”
When ST266 was given to the MS mice via their nose, it reached the central nervous system within 30 minutes and was detected at higher concentrations in parts of the eye and optic nerve compared to other areas of the brain. These findings demonstrated that this type of delivery can target tissues of the eye, which is easier, less painful, and less invasive than injecting medication directly into the eye.
In mice with optic neuritis, the team showed that early treatment with ST266 prevented damage and dysfunction, marked by significantly reduced loss of optic nerve cells, and suppression of inflammatory cell infiltration into the optic nerve. This in turn was associated with limitation of the degree of demyelination caused by MS- related optic neuritis. However, “it’s not known if these effects are independent effects of the therapy or interdependent effects,” Shindler said.
Treatment of later-stage optic neuritis in the MS mice showed similar results, resulting in improved visual function compared to untreated groups. The data suggest that ST266 helps promote optic neuron survival by potentially activating multiple pathways, including those that prevent cell death.
“These results are particularly important as the preservation of retinal cells is a significant factor when treating optic neuritis,” Shindler said. “There is an increased need for combination treatment options that are able to prevent nerve-cell axon loss for patients with optic neuritis.”
Currently, the only acute treatment for MS-related optic neuritis is IV steroids, which only hasten whatever amount of visual recovery will occur even without treatment. Steroids do not prevent nerve damage or permanent vision loss. “ST266’s ability to preserve vision in the preclinical model and reduce neuronal loss would be a huge advance if it translates to human patients,” Shindler said.
The study also has implications beyond MS-related optic problems. “We also showed an effect on cultured neurons, suggesting that effects may translate to other optic nerve diseases, as well as other brain neurodegenerative diseases,” Shindler said.
Funding: Dr. Shindler has served as a scientific advisory board member and received consulting fees from Noveome (formerly Stemnion, Inc.). In addition, Noveome has provided unrestricted funds to Penn to support research in Dr. Shindler’s laboratory.
Source: Karen Kreeger – University of Pennsylvania
Image Source: NeuroscienceNews.com image is credited to Ken Shindler, MD, PhD, Perelman School of Medicine, University of Pennsylvania.
Original Research: Full open access research for “Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model” by Reas S. Khan, Kimberly Dine, Bailey Bauman, Michael Lorentsen, Lisa Lin, Helayna Brown, Leah R. Hanson, Aleta L. Svitak, Howard Wessel, Larry Brown & Kenneth S. Shindler in Scientific Reports. Published online January 31 2017 doi:10.1038/srep41768
Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model
The ability of a novel intranasally delivered amnion cell derived biologic to suppress inflammation, prevent neuronal damage and preserve neurologic function in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis was assessed. Currently, there are no existing optic nerve treatment methods for disease or trauma that result in permanent vision loss. Demyelinating optic nerve inflammation, termed optic neuritis, induces permanent visual dysfunction due to retinal ganglion cell damage in multiple sclerosis and experimental autoimmune encephalomyelitis. ST266, the biological secretome of Amnion-derived Multipotent Progenitor cells, contains multiple anti-inflammatory cytokines and growth factors. Intranasally administered ST266 accumulated in rodent eyes and optic nerves, attenuated visual dysfunction, and prevented retinal ganglion cell loss in experimental optic neuritis, with reduced inflammation and demyelination. Additionally, ST266 reduced retinal ganglion cell death in vitro. Neuroprotective effects involved oxidative stress reduction, SIRT1-mediated mitochondrial function promotion, and pAKT signaling. Intranasal delivery of neuroprotective ST266 is a potential novel, noninvasive therapeutic modality for the eyes, optic nerves and brain. The unique combination of biologic molecules in ST266 provides an innovative approach with broad implications for suppressing inflammation in autoimmune diseases, and for preventing neuronal damage in acute neuronal injury and chronic neurodegenerative diseases such as multiple sclerosis.
“Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model” by Reas S. Khan, Kimberly Dine, Bailey Bauman, Michael Lorentsen, Lisa Lin, Helayna Brown, Leah R. Hanson, Aleta L. Svitak, Howard Wessel, Larry Brown & Kenneth S. Shindler in Scientific Reports. Published online January 31 2017 doi:10.1038/srep41768