Researchers have tested a new compound called ST266 in a mouse model of multiple sclerosis (MS) and found that its anti-inflammatory properties prevent the loss of cells related to optic neuritis — a condition that leads to vision loss.
The study, “Intranasal Delivery of a Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function in a Mouse Multiple Sclerosis Model,” appeared in the journal Scientific Reports.
Optic neuritis, an inflammatory demyelinating disease of the optic nerve, is the most common symptom of MS and involves a spectrum of visual changes ranging from mild to complete visual loss. Although optic neuritis often causes limited visual problems, up to 60 percent of patients develop permanent vision loss.
ST266 combines biologic molecules that contain multiple anti-inflammatory cytokines and growth factors, and was developed to stimulate paracrine signaling — a form of cell-to-cell communication in which a cell produces a signal to induce changes in adjacent cells, altering the behavior or differentiation of those 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,” Kenneth Shindler, MD, PhD, said in a news release.
Schindler, the study’s lead author, is an associate professor of ophthalmology and neurology at the University of Pennsylvania’s Perelman School of Medicine. Collaborating with Pittsburgh-based Noveome Biotherapeutics, Shindler and colleagues gave ST266 to mice models of MS via their nose. The compound reached the animals’ central nervous systems within 30 minutes and was spotted at higher concentrations in parts of the eye and optic nerve.
Delivering the compound via the nose can target tissues of the eye — a far less invasive method than injecting a drug agent directly into the eye.
In mice with MS and optic neuritis, ST266 was found to attenuate visual dysfunction and prevent retinal ganglion cell loss, with reduced inflammation and demyelination.
“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.” Shindler said, adding that “it’s not known if these effects are independent effects of the therapy or interdependent effects.”
When researchers used ST266 to treat MS mice with later-stage optic neuritis, the results were similar and led to visual improvement compared to untreated mice.
The findings indicate that ST266 offers an innovative approach with broad implications for suppressing inflammation in autoimmune diseases, and for preventing neuronal damage in chronic neurodegenerative diseases such as MS.
“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.”
MS-related optic neuritis is usually treated with intravenous (IV) steroids, which 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,” said Shindler, concluding that his team’s findings also have implications for other diseases. “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.”
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