Anti-cell death agent a potential treatment for vision loss associated with multiple sclerosis

February 9, 2017
This image shows myelin (blue) in the optic nerve of a normal mouse (top), a mouse with optic neuritis (middle), and an optic neuritis mouse treated with ST266 (bottom). Credit: Ken Shindler, MD, PhD, Perelman School of Medicine, 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 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 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.

Explore further: Researchers discover reason for permanent vision loss after head injury

More information: Reas S. Khan et al, Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model, Scientific Reports (2017). DOI: 10.1038/srep41768

Related Stories

Researchers discover reason for permanent vision loss after head injury

February 8, 2017
Research from The University of Texas Medical Branch in Galveston has shed new light on what causes the permanent vision loss sometimes seen in the wake of a head injury. The findings are detained in The American Journal ...

Stress pathway identified as potential therapeutic target to prevent vision loss

February 8, 2012
A new study identifies specific cell-stress signaling pathways that link injury of the optic nerve with irreversible vision loss. The research, published by Cell Press in the February 9 issue of the journal Neuron, may lead ...

Epilepsy drug could protect nerves from damage in multiple sclerosis

January 25, 2016
An epilepsy drug could lead to a new treatment that protects nerve damage in MS patients, according to research published in the Lancet Neurology.

Scientists find that stem cell exosomes promote survival of retinal ganglion cells in rats

January 27, 2017
A new study in rats shows that stem cell secretions, called exosomes, appear to protect cells in the retina, the light-sensitive tissue in the back of the eye. The findings, published in Stem Cells Translational Medicine, ...

AAN: phenytoin neuroprotective in optic neuritis

April 17, 2015
(HealthDay)—Phenytoin appears to be neuroprotective in acute optic neuritis (AON), according to a study scheduled to be presented at the annual meeting of the American Academy of Neurology, held from April 18 to 25 in Washington, ...

Recommended for you

Study indicates proof of concept for using a surrogate liquid biopsy to provide genetic profile of retinoblastoma tumors

October 12, 2017
Retinoblastoma is a tumor of the retina that generally affects children under 5 years of age. If not diagnosed early, retinoblastoma may result in loss of one or both eyes and can be fatal. Unlike most cancers that are diagnosed ...

Farsighted children struggle with attention, study finds

October 10, 2017
Farsighted preschoolers and kindergartners have a harder time paying attention and that could put them at risk of slipping behind in school, a new study suggests.

New drug reduces rate of progression of incurable eye disease

October 4, 2017
An international study including researchers from the Centre for Eye Research Australia (CERA) has found a way to slow the progression of dry age-related macular degeneration (AMD) - one of the most common causes of vision ...

Gene therapy shows promise for reversing blindness

October 2, 2017
Most causes of untreatable blindness occur due to loss of the millions of light sensitive photoreceptor cells that line the retina, similar to the pixels in a digital camera.

Discovery provides glimmer of hope to prevent blindness

September 27, 2017
Macquarie University researchers have discovered that a naturally occurring protein in the body protects the eye from the common eye disease glaucoma, and which is particularly sensitive to oxidation through environmental ...

Coming soon: Glaucoma self-care, from home?

September 23, 2017
(HealthDay)—For many glaucoma patients, repeat trips to a doctor's office to check on their eyes can be a real pain.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.