If finding a way to restore nerve cells’ protective coating were the only challenge, multiple sclerosis would be a more manageable disease.
But researchers at the UConn Health Center say MS also takes it toll on axons, the nerve cell extensions that carry nerve impulses.
The devastation hinders the ability of neurons to communicate with each other, resulting in debilitating neurodegenerative disease.
“The long-term disability of MS is caused by degeneration of axons that have lost their myelin sheath – their protective coating,” says Rashmi Bansal, an associate professor of neuroscience.
Bansal recently won a grant from the National Multiple Sclerosis Society for her research focusing on a specific protein and its role in MS.
In MS patients and mouse models, this protein, called fibroblast growth factor, increases in areas of the nervous system where the myelin is missing.
“There’s got to be an important connection of this observation with the disease scenario,” Bansal says.
Signals from these growth factors regulate the biology of cells called oligodendrocytes, which produce myelin in the central nervous system.
Fibroblast growth factors bind and signal to oligodendrocytes through three different receptors, which are the docking sites for these growth factors. Bansal’s previous research found this interaction varied depending on the receptor involved.
“Stimulation of one receptor versus the other led to different responses,” Bansal says. “And interestingly, we found that in oligodendrocytes, while one response was positive, the other was a negative pathological one.
So that raises the question of what the fibroblast growth factor is doing. Is it good or bad to have a lot of it in MS lesions?”
Bansal’s grant, more than $600,000 over three years, is for the next step. She and her research team, including postdoctoral fellow Miki Furusho, are working with mice that are missing the gene for one or more of the fibroblast growth factor receptors.
“We want to know, what’s the outcome of getting rid of this gene? It would give us a handle on what each receptor is doing for normal myelination in the animal,” Bansal says.
“But what would be really interesting and important for MS research will be to know the function of these receptors in myelin disease and recovery.”
Bansal says initial studies with these mice have given indications of defects in oligodendrocyte development and myelination, “but how it’s going to play out in the disease scenario, we don’t know yet. In this grant we have proposed experiments that will allow us to address these questions.”
In addition to her own research projects, Bansal is committed to carrying on the work of professor of neuroscience Steven Pfeiffer, a colleague who died last year.
During his 38 years at the Health Center, Pfeiffer developed an international reputation as a biomedical scientist working toward a cure for MS.
“He and I worked together on various aspects of MS research ever since I joined the University,” Bansal says.
Bansal says MS research at UConn is embracing modern scientific advances such as proteomic analysis, an approach aimed at discovering new proteins.
Bansal and her team, including postdoctoral fellow Akahiro Ishii, will continue the pursuit of the proteins in human myelin, which was a major focus of Pfeiffer’s research.
“Myelin composition is well known to have some major proteins,” Bansal says.
“This proteomic analysis allows us to determine the minor components – and minor doesn’t mean unimportant: the smallest components could be the ones that are the most important. This study will provide us with several novel targets to go after and will form a valuable foundation for understanding the molecular mechanism of myelination and the pathogenesis of human myelin disease such as MS.”
The MS Society also awarded Bansal two other grants since 1999, and she has won funding from the National Institutes of Health over that same period.
“Our goal – like many researchers – is that somehow in our lifetime we’ll be able to see our research from the bench get into the clinics and help the people with multiple sclerosis,” Bansal says.
“That’s the main ambition and dream for us.”