IndCl Could Help Improve Vision in Patients With Multiple Sclerosis
By: Sai Srihaas Potu
Multiple sclerosis is a chronic disease that affects the central nervous system, especially the brain, spinal cord, and optic nerves. This can lead to a wide range of symptoms throughout the body. It is not possible to predict how multiple sclerosis (MS) will progress in any individual. Some people have mild symptoms, such as blurred vision and numbness, and tingling in the limbs. In severe cases, a person may experience paralysis, vision loss, and mobility problems.
It is difficult to know precisely how many people have MS. According to the National Institute for Neurological Disorders and Stroke, 250,000–350,000 people in the United States are living with MS. The National Multiple Sclerosis Society estimates the number could be closer to 1 million. However, new treatments are proving effective at slowing the disease.
Scientists do not know exactly what causes MS, but they believe it is an autoimmune disorder that affects the central nervous system (CNS). When a person has an autoimmune disease, the immune system attacks healthy tissue, just as it might attack a virus or bacteria. In the case of MS, the immune system attacks the myelin sheath that surrounds and protects the nerve fibers, causing inflammation. Myelin also helps the nerves conduct electrical signals quickly and efficiently.
As more lesions develop, nerve fibers can break or become damaged. As a result, the electrical impulses from the brain do not flow smoothly to the target nerve. This means that the body cannot carry out certain functions.
In a new study, researchers have reported that IndCl, a drug that improves myelination and reduces motor disability, appears to improve visual problems associated with multiple sclerosis.
A team led by a biomedical scientist at the University of California, Riverside, reports a drug — an estrogen receptor ligand called indazole chloride (IndCl) — has the potential to improve vision in patients with multiple sclerosis or MS. The study was performed on mice induced with a model of MS and the first to investigate IndCl’s effect on the pathology and function of the complete afferent visual pathway. The afferent visual pathway includes the eyes, 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 away at the protective covering of nerves, the initial period of inflammation and demyelination often damages the optic nerve and other parts of the visual system first. As a result, approximately 50% of patients with MS experience optic neuritis — inflammatory demyelination of the optic nerve — before showing initial symptoms. Almost all MS patients have impaired vision at some point during disease progression. Symptoms can include eye pain, blurred vision, and progressive vision loss that can lead to blindness, among other visual impairments.
The optic nerve, a heavily myelinated bundle of nerves located at the back of the eye, transfers visual information from the retina to the vision centers of the brain through electrical impulses. Myelin acts as an insulating substance that speeds the transmission of these electrical impulses. Partial myelin loss slows the transmission of visual information; severe myelin loss may stop the signal altogether.
The researchers used IndCl to assess its impact on demyelinating visual pathway axons. The treatment induced remyelination and mitigated some damage to the axons that resulted in partial functional improvement in vision.
The visual pathway in mice is similar to that in humans. The mouse brain is, therefore, an excellent model for scientists to study vision impairment. In the lab, Tiwari-Woodruff and her research group first induced the mouse model of MS. They let the disease progress for about 60 days and when the disease reached a peak between 15 and 21 days, they administered IndCl to half the mice.
At the end of the experiment, they performed a functional assay to measure the visual electrical signal; and immunohistochemistry to examine the visual pathway. The mice that received the drug showed improvement in myelination, with visual function improving by about 50%.
Currently approved MS drugs reduce inflammation but do not prevent neurodegeneration or initiate remyelination. Further, they only partially prevent the onset of permanent disability in patients with MS.
The researchers treated the MS mice with IndCl at peak disease. They believe that if the brain is highly diseased, some of the axons that could potentially restore visual function are too damaged and will not recover. In their paper, the authors mentioned that early treatment can recover 75%-80% of the original function.
There is a strong and urgent need to find a therapeutic candidate that restores neurological function in patients with MS. Therapeutics must target remyelination and prevent further axonal degeneration and neuronal loss. The researchers believe that the good estrogens, which have neuroprotective and immunomodulatory benefits, could be candidates for MS treatment.
MS is a potentially severe health condition that affects the nervous system. The progression of MS is different for each person, so it is hard to predict what will happen, but most people will not experience severe disability.
In recent years, scientists have made rapid progress in developing drugs and treatments for MS. Newer drugs are safer and more effective, and they offer significant hope for slowing disease progression.
As researchers learn more about genetic features and changes that occur with MS, there is also hope that they will be able to predict more easily which kind of MS a person will have and establish the most effective treatment from the earliest stage.
1. Balk LJ, Steenwijk MD, Tewarie P, Daams M, Killestein J, Wattjes MP, et al. Bidirectional trans‐synaptic axonal degeneration in the visual pathway in multiple sclerosis. Journal of Neurology, Neurosurgery, and Psychiatry. 2015.
2. Mowry EM, Loguidice MJ, Daniels AB, Jacobs DA, Markowitz CE, Galetta SL, et al. Vision related quality of life in multiple sclerosis: correlation with new measures of low and high contrast letter acuity. Journal of Neurology, Neurosurgery, and Psychiatry. 2009.
3. Tiwari-Woodruff et al. Alleviation of extensive visual pathway dysfunction by a remyelinating drug in a chronic mouse model of multiple sclerosis. Brain Pathology. 2021.