Multiple sclerosis (MS) has baffled physicians and researchers since its symptoms were first described by Jean-Martin Charcot in the 1860s. The disease, which attacks the central nervous system, can range from relatively benign to somewhat disabling all the way to devastating as communication between the brain and the body is disrupted.

The new NMSS grant will help develop and evaluate novel therapies that can manipulate the immune system to better treat MS, a disease that has no cure, says Etty Benveniste, principal investigator and chair of the Department of Cell Biology.

The National Multiple Sclerosis Society (NMSS) recently awarded UAB a prestigious Collaborative Multiple Sclerosis Research Center Award to help find answers for this chronic, unpredictable disease. The five-year, $742,602 grant creates an NMSS center that partners UAB’s nationally renowned MS researchers with other research faculty who have complementary research interest and expertise, but have never worked in the MS field.

“The NMSS funds between two and four of these collaborative MS research center grants each year, so not many institutions have this type of grant,” says Etty “Tika” Benveniste, Ph.D., principal investigator and char of Cell Biology. “This highlights the existing excellence in MS research that is evident at UAB and the hope and goal that we will be able to bring more new people into the field and really push the envelope in MS-related research.”

The purpose of the grant is to develop and evaluate novel therapies that can manipulate the immune system to better treat MS, a disease that has no cure.

“We have four projects that all are interdisciplinary and involve established investigators in the field of MS coupled with new investigators who are working in fields including Parkinson’s disease, neuro-developmental diseases, arthritis, psychiatric diseases and spinal cord injury,” Benveniste says. “The grant provides support for people to work in these laboratories and an infrastructure for this group to get together on a regular basis and to have research symposia.”

The award is expected to provide the infrastructure for the recruitment of new faculty interested in MS or related diseases. It also has a strong educational component and provides training opportunities for graduate students, post-doctoral fellows and medical residents.

Known quantities
That MS and its symptoms have been recognized for more than 140 years with no cure and no definite known cause is “amazing,” says Benveniste.

One known quality of the disease is that it is triggered by an overactive immune system. Immune-system cells are able to traffic through the blood-brain barrier when that barrier should keep the brain sequestered from the immune system. Once the activated immune cells get into the brain they begin producing toxic molecules.

The thought is that perhaps there is a way to prevent the entry of these cells into the brain or inhibit them in some way so they no longer can produce the toxic molecules.

“We’re trying to understand how we can dampen this activated immune response and inflammatory response that is the cause of myelin damage and neuronal loss — both hallmarks of MS,” Benveniste says. “We’re trying to prevent those two detrimental events.”

Fresh ideas
The NMSS hopes that bringing in researchers who have never worked in the field of MS will bring about fresh research ideas. They hope it will lead to locating the cause of the disease and bring about therapies to treat and prevent it.

Rita Cowell, Ph.D., assistant professor in psychiatry, and Candace Floyd, Ph.D., assistant professor of physical medicine and rehabilitation, are two of the researchers who will be looking into MS for the first time.

Cowell’s lab research focuses on neurodevelopmental disorders. She hopes her research might shed some light on the substantial cognitive impairment in MS.

“Recent evidence suggests that particular interneurons in the brain involved in learning and memory are sensitive to brain inflammation,” Cowell says. “If we could figure out how to protect these cells from inflammatory damage in MS, we may be able to ameliorate some of the profound cognitive deficits in patients with MS.

Floyd’s research is on traumatic spinal cord injury and her expertise in evaluating locomotion and sensation.

“Spinal cord injury and multiple sclerosis involve similar cell types and pathophysiological processes,” Floyd says, “and knowledge learned from the study of one could likely contribute to the understanding of the other.”

David Standaert, M.D., Ph.D, director of the Center for Neurodegeneration and Experimental Therapeutics, also is new to the field of MS research. His interest comes from the recent recognition of the role of the immune system in many brain diseases and the increasing overlap between MS and other brain disorders.

“MS long has been considered an immune-mediated disease, but in recent years it has become clear that there also is a degenerative component that may account for much of the long-term decline in function seen in the disease,” Standaert says. “Parkinson’s, Alzheimer’s and similar disorders, in contrast, have been thought of as primarily degenerative. But increasing evidence points to a prime role of the immune system and neuro-inflammation in neuro-degeneration.

“I hope the NMSS Collaborative Research Center will foster cross-cultural thinking about the inter-relationships between immune-mediated events and neurodegeneration, and that a clearer understanding of the mechanisms of neuro-inflammation and neuro-degeneration may lead to therapies which are broadly effective in these disorders,” Standaert says.

Co-investigators on the grant also include Khurram Bashir, M.D., associate professor of neurology, and John Rinker, M.D., assistant professor of neurology, ensuring that the research and clinical arms will work closely together with the ultimate goal to develop drugs that can be taken to the bedside.

The NMSS Collaborative Research Center also hopes to partner with the UAB Center for Pediatric Onset of Demyelinating Disease (CPODD) — the only clinic in the Southeast dedicated to treating children with demyelination.

Other grant co-principal investigators are: Scott Barnum, Ph.D.; Michael Brenner, Ph.D.; Patrizia DeSarno, Ph.D.; Richard Jope, Ph.D.; Peter King, M.D.; Chandar Raman, Ph.D.; and Alex Szalai, Ph.D.

The center will begin holding monthly meetings soon. Contact Benveniste at tika@uab.edu if you would like to participate or for more information.