Remyelinating drugs have shown potential to improve vision in MS patients

A team led by a biomedical researcher at the University of California, Riverside reports that a drug, an estrogen receptor ligand called IndCl chloride (IndCl), may improve vision in patients with multiple sclerosis (MS). I am.

This study, conducted in mice model-induced with MS, was the first to investigate the effect of IndCl on the pathology and function of the fully afferent visual pathway. Brain pathology.. The afferent visual pathway includes the eye, optic nerve, and all brain structures responsible for receiving, transmitting, and processing visual information.

In MS, a disease in which the immune system “demyelinates” or eats up the protective coating of nerves, the initial period of inflammation and demyelination often causes damage to the optic nerve and other parts of the visual system first. As a result, about 50% of MS patients experience optic neuritis (inflammatory demyelination of the optic nerve) before they show early symptoms. Almost all MS patients have diminished vision at some point during the course of their illness. Symptoms include, among other visual impairments, eye pain, blurred vision, and progressive loss of vision that can lead to blindness.

The optic nerve is a bundle of myelinated nerves behind the eye that transfers visual information from the retina to the visual center of the brain via electrical impulses. Myelin acts as an insulator that accelerates the transmission of these electrical impulses. Partial myelin loss slows the transmission of visual information. Severe myelin loss can completely stop the signal.

Researchers used IndCl to evaluate the effect on demyelinating visual pathway axons. Treatment induced myelin sheath remodeling, reduced damage to axons, and resulted in partial improvement in visual acuity.

IndCl has previously been shown to reduce movement disorders, increase myelination, and promote neuroprotection of the spinal cord and corpus callosum in mice. However, its effect on the visual system has not been evaluated so far. Our study shows that the optic nerve and optic tract, which suffer from severe inflammation, demyelination, and axonal damage, can recover some function with IndCl treatment with diminished inflammation and increased remyelination. .. “

Seema Tiwari-Woodruff, Professor of Biomedical Sciences, University of California, Riverside School of Medicine and Lead Author of Research

The visual pathway of a mouse is similar to that of a human. Therefore, the mouse brain is an excellent model for scientists to study visual impairment. In the lab, Tiwari-Woodruff and her research group first induced a mouse model of MS. They progressed the disease for about 60 days, and when the disease peaked between the 15th and 21st, they administered IndCl to half of the mice. At the end of the experiment, they performed a functional assay to measure the visual electrical signal. Immunohistochemistry for examining the visual pathway. Mice treated with the drug showed improved myelination and visual function improved by about 50%.

For Tiwari-Woodruff, the next question is how IndCl treatment induces functional myelin remodeling of the visual pathway. Her lab is collaborating with John A. Katzenerenbergen’s lab, co-author of the University of Illinois at Urbana-Champaign, to investigate new drugs that are similar to IndCl.

“A more effective treatment that protects axons, stimulates axonal myelinary remodeling, and prevents ongoing axonal damage by measuring visual function and recovery in the presence of new therapies. Can be screened, “says Tiwari-Woodruff.

Currently approved MS drugs reduce inflammation, but do not prevent neurodegeneration or initiate myelin sheath remodeling. In addition, they only partially prevent the development of permanent disability in MS patients.

“MS mice were treated with IndCl at the peak of the disease,” said Tiwari-Woodruff. “If the brain is highly ill, some of the axons that can restore visual function are too damaged to recover. There are irreversible points. Treatment to improve vision It emphasizes the need to start early. Early treatment is possible. It restores 75% to 80% of its original function. “

Tiwari-Woodruff says that additional research is needed, but new findings show the dynamics of visual pathway dysfunction and impairment in MS mice, along with the importance of early treatment to reduce axonal injury. Emphasized.

“There is a strong and urgent need to find potential treatments to restore neural function in MS patients,” said Tiwari-Woodruff. “Therapeutic agents need to target myelin sheath remodeling and prevent further axonal degeneration and neuronal loss. Excellent estrogens with neuroprotective and immunomodulatory benefits may be candidates for MS treatment. there is.”