“Famous” Physical Therapists Bob Schrupp and Brad Heineck provide information on foot drop.
Multiple Sclerosis
“Researchers have developed a drug that may improve the vision of patients with multiple sclerosis through remyelination.”
UC Riverside-led mouse study stresses MS treatment should be started early
A team led by a biomedical scientist at the University of California, Riverside, reports that a drug, an estrogen receptor ligand called indazole chloride (IndCl), has the potential to improve vision in patients with multiple sclerosis (MS).
The study, conducted on mice induced with a model of MS, was the first to investigate the effect of IndCl on the pathology and function of the complete afferent visual pathway. It is published in Brain Pathology. The afferent visual pathway includes the eyes, optic nerve, and all brain structures responsible for receiving, transmitting, and processing visual information.
In multiple sclerosis (MS), the immune system attacks the protective covering of nerves, causing inflammation and damage to the optic nerve and other parts of the visual system. Around 50% of MS patients experience optic neuritis, which is inflammation and demyelination of the optic nerve, before showing initial symptoms. Almost all MS patients suffer from impaired vision at some point during the progression of the disease. Symptoms may include eye pain, blurred vision, and progressive vision loss that can ultimately lead to blindness, among other visual impairments.
The optic nerve, which is 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 up the transmission of these electrical impulses. Partial myelin loss slows down the transmission of visual information, and severe myelin loss may even stop the signal altogether.
The researchers utilized IndCl to evaluate its impact on demyelinating visual pathway axons. The therapy prompted remyelination and alleviated some damage to the axons, resulting in partial improvement in vision function.
“Seema Tiwari-Woodruff, a professor of biomedical sciences at the UC Riverside School of Medicine and the study’s lead author, stated that IndCl has previously been shown in mice to reduce motor disability, increase myelination, and provide neuroprotection in the spinal cord and corpus callosum. However, its effects in the visual system had not been evaluated until now. Our study demonstrates that the optic nerve and optic tract, which undergo significant inflammation, demyelination, and axonal damage, show some restoration of function with IndCl treatment, along with successful reduction in inflammation and an increase in remyelination.”
The visual pathway in mice is similar to that in humans, making the mouse brain an excellent model for studying 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. When the disease reached a peak between 15 and 21 days, 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 and conducted immunohistochemistry to examine the visual pathway. The mice that received the drug showed improvement in myelination, with visual function improving by about 50%.
“Measuring visual function and recovery in the presence of new therapies can be used to screen more effective treatments that will protect axons, stimulate axon remyelination, and prevent ongoing axon damage,” Tiwari-Woodruff said.
Currently approved MS drugs reduce inflammation but do not prevent neurodegeneration or initiate remyelination. Furthermore, they only partially prevent the onset of permanent disability in patients with MS.
“We treated the mice with IndCl at the peak of their disease,” said Tiwari-Woodruff. “If the brain is highly diseased, some of the axons that could potentially restore visual function are too damaged and will not recover. There’s a point of no return. Our research emphasizes that in order to achieve vision improvement, treatment must begin early. Early treatment can restore 75%-80% of the original function.”
Tiwari-Woodruff stressed that although additional studies are required, the new findings show the dynamics of visual pathway dysfunction and disability in MS mice, along with the importance of early treatment to mitigate axon damage.
“There is a strong and urgent need to find a therapeutic candidate that restores neurological function in patients with MS,” Tiwari-Woodruff said. “Therapeutics must target remyelination and prevent further axonal degeneration and neuronal loss. The good estrogens, which ha
Dr Sarah Morrow and cognitive impairment in MS patients
“A model that helps to explain why some patients with multiple sclerosis experience seizures.”
This is an image from the research is featured on the cover of volume 346 (pages 409-422) of the journal <i>Neuroscience</i>. CREDIT Elsevier.
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that affects nearly 2.3 million people worldwide. MS is triggered when the immune system attacks the protective covering around nerve fibers, called the myelin sheath. The resulting “demyelination” damages nerve cells and impairs the exchange of information between the brain and body and within the brain itself.
When the protective covering around nerve fibers wears off, nerve signals can slow down or stop. Depending on where the damage occurs, this can lead to impaired vision, sensation, and use of limbs. If the disease destroys nerve fibers, it can lead to permanent paralysis.
“In addition to this, individuals with multiple sclerosis (MS) are three to six times more likely to develop seizures—abnormal hyperactivity of nerve cells—compared to the rest of the population. Despite this increased occurrence, little research has been conducted to explore the reasons behind these seizures in MS patients.”
In a mouse model, a team of scientists at the University of California, Riverside, has discovered that chronic demyelination is closely linked to, and likely the cause of, seizures. The researchers reported their findings in the journal Neuroscience. They also observed that specific neurons in the brain, known as “parvalbumin interneurons,” which are crucial for controlling hyperactivity, undergo changes and are lost when extensive demyelination occurs in the brain’s cortex and hippocampus.
“Demyelination causes damage to axons and neuronal loss. Specifically, parvalbumin interneurons are lost in mice, resulting in a shift from reduced activity to increased activity, which could be a cause of seizures,” explained Seema Tiwari-Woodruff, an associate professor of biomedical sciences in the UC Riverside School of Medicine, whose laboratory conducted the research. “It’s highly likely that this is also happening in MS patients who experience seizures.”
Tiwari-Woodruff and her team induced demyelination in mice in the lab by feeding them a diet containing cuprizone, a copper-binding substance that causes damage to oligodendrocytes, the brain cells that produce myelin. After nine weeks of being fed cuprizone, the majority of the mice started having seizures.
“Without myelin, axons are vulnerable,” said Tiwari-Woodruff. “They develop blebs – ball-like structures that hinder the transport of important proteins and conduction of electrical signals. In some instances, significant axon damage can lead to neuronal loss. In both MS and our mouse model, parvalbumin interneurons are more vulnerable and likely to die. This causes the inhibition to be removed and induce seizures. Thus, axonal and neuronal survival may be directly tied to the trophic support provided by myelin.”
In another study, after nine or twelve weeks, the researchers stopped feeding the mice the cuprizone diet. Oligodendrocytes began to repopulate the demyelinated areas and remyelinate the intact but myelin-stripped axons. Future studies will assess seizure activity with remyelination.
“Does remyelination affect seizure activity? Can we accelerate remyelination with drugs to provide relief for MS patients? We are interested in addressing these questions,” Tiwari-Woodruff said.
Her team recently received a pilot grant from the National Multiple Sclerosis Society. They will be comparing postmortem brain tissue from MS patients with seizures to those without in order to understand the cellular basis of seizures in MS. Additionally, they will use their findings to assess how accurately the cuprizone mouse model replicates the changes observed in humans.
“We want to know if the tissues exhibit the same characteristics as those in our mouse model,” said Tiwari-Woodruff. “Our initial findings in postmortem tissue indicate significant similarities between the two. We now have a mouse model that we can utilize to test and propose potential therapeutic treatments. Once developed, these drugs, designed to reduce hyperactivity and decrease the occurrence of seizures, could also benefit patients with epilepsy.”
Dr. Ruth Ann Marrie discusses comorbidities in multiple sclerosis.
Ruth Ann Marrie, MD, PhD, director of the Multiple Sclerosis Clinic at the University of Manitoba, discusses the overall prevalence of comorbidities in patients with multiple sclerosis (MS).