Nasal Solution Made of ‘Molecular Soup’ Protects Eye Neurons in MS Mice with Optic Neuritis

A treatment delivered as a nasal solution helped to preserve eye neurons and improve eyesight in a mouse model of multiple sclerosis (MS), a recent study demonstrated — suggesting that it may be possible to deliver drugs that target the brain in this noninvasive way.

But nasal administration is not the only novelty of this treatment. The drug, developed by Noveome Biotherapeutics, is virtually a molecular soup, a complex solution secreted by cells derived from the membrane that covers an embryo. This soup, called a secretome, has been shown to have powerful wound-healing properties that, it turns out, are also active within the brain.

“We believe this is the first demonstration of a potentially successful therapeutic treatment of the optic nerve using intranasal delivery of large molecular weight biomolecules,” Larry Brown, ScD, chief scientific officer of Noveome, said in a press release.

The study, “Intranasal Delivery of a Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function in a Mouse Multiple Sclerosis Model,” was published in the journal Scientific Reports.

Noveome worked with researchers at the Perelman School of Medicine at the University of Pennsylvania to test the treatment in mice with experimental autoimmune encephalomyelitis, a common MS mouse model.

One of the main features of these mice, mirrored in patients, is the presence of optic neuritis. This inflammation and demyelination of retinal ganglion cells in the optic nerve eventually leads to neuron death and eyesight diminution and loss.

Experiments showed that the treatment, called ST266, reached the central nervous system within 30 minutes of nasal administration. The compound was found in higher concentration in the eye and optic nerve than in the brain, indicating that it is particularly suitable for treating optic neuritis.

When researchers treated mice in early stages of optic neuritis, the treatment reduced the migration of inflammatory cells into the optic nerve, lowered the extent of demyelination, and reduced the loss of retinal ganglion cells.

Mice in later stages of the condition also benefitted from the treatment. In this group, ST266 reduced neuron damage and improved eyesight compared to untreated mice.

“Current therapies reduce inflammation but fail to prevent retinal ganglion cell loss; thus, there is a need for combination treatment options that are able to prevent retinal ganglion cell axon loss for patients with optic neuritis,” said Kenneth S. Shindler, MD, a professor of Ophthalmology at Perelman and Noveome’s research partner.

“These results are particularly important as the preservation of retinal ganglion cells has been recognized as a significant factor when treating optic neuritis due to potential permanent visual dysfunction.”

Researchers also examined the molecular pathways that mediated the treatment’s effect. It was clear that the mix that makes up ST266 had antioxidative properties, improved mitochondrial work, and acted on a well-known pathway called p-Akt that is known to prevent cell death and promote growth.

“The unique and diverse biologic molecules present in ST266 were seen to help promote anti-inflammatory and neuroprotective activity in this preclinical model and suggest that ST266 has the potential to mediate neuroprotection through activation of multiple intracellular signaling pathways,” Shindler said.

Earlier studies of the molecules secreted by stem cells in the amnion — the membrane covering a developing embryo — have shown that the molecules contribute to lowering inflammation and promote wound healing. But this was the first time that it was tested as a means of saving nerve cells in living animals.

“These promising results reinforce the multifaceted potential of ST266 in multiple disease areas, including disorders in the back of the eye,” Brown said. “The study also reconfirmed the safety profile and potent nature of ST266 in a preclinical model, which provides encouragement and support for continued research.”