Wayne State University

WSU researchers capture 25 percent of DOD's Concept Award grants

 Alexander Gow
 Jeffrey Loeb
 Fei Song

Researchers at the Wayne State University School of Medicine have captured 25 percent of the U.S. Department of Defense’s 2010 Concept Award grants to fund multiple sclerosis studies.

Alexander Gow, Ph.D., professor and Charles H. Gershenson Distinguished Fellow of the Wayne State University Center for Molecular Medicine and Genetics, the Department of Pediatrics and the Department of Neurology, received one of the grants. Jeffrey Loeb, M.D., Ph.D., associate professor of the Department of Neurology and associate director of the Center of Molecular Medicine and Genetics, and Fei Song, M.D., Ph.D., assistant professor of Neurology and the Center for Molecular Medicine and Genetics, received the other.

The one-year grants are each for $114,000, and come through the U.S. Army Medical Research and Material Command, Office of the Congressionally Directed Medical Research Programs.

Of 120 research project submissions, only eight received such grants.

The project overseen by Dr. Loeb and Dr. Song will test a new drug -- HBD-S-H4, or GlyB4 – in mice with the symptoms of multiple sclerosis to determine its effects in disrupting neuregulin1. NRG1 is a brain-produced protein that regulates many normal functions in the brain, but may also have effects on immune system activation. The protein could serve as a potential therapeutic target for disorders such as multiple sclerosis.

“The drug was entirely developed by our group at Wayne State University, and the core technology behind the drug is protected by patents worldwide,” said Dr. Loeb, who also serves with the WSU Hiller Amyotrophic Lateral Sclerosis Center. “It is a novel, targeted antagonist to the growth factor neuregulin that has potential uses in diseases that vary from chronic pain to cancer. It is unique because it uses the same targeting system developed by nature to get drugs where they are needed in the body and not harm other areas.”

Dr. Loeb will serve as the principal investigator of “Therapeutic Value or Harm of Neuregulin 1 in Demyelinating Disorders” and Dr. Song will serve as co-investigator.

In multiple sclerosis, the body’s immune system attacks the brain and gradually destroys it, typically over many years. The brain, for the most part, can be divided into gray and white areas. Neurons are located in the gray area, and the white parts are where the neurons send their axons -- similar to electrical cables carrying messages -- to communicate with other neurons or muscles. The white parts of the brain are white because oligodendrocyte cells manufacture a cholesterol-rich membrane called myelin that coats the axons. The myelin’s function is to insulate the axons, much like the plastic coating on an electrical cable. In addition, the myelin speeds communication along axons and makes communication more reliable. That myelin sheathing is attacked and broken down by the immune system of a patient with MS.

The National Multiple Sclerosis Society estimates that there are 400,000 Americans living with MS, and 200 more diagnosed each week. Worldwide, the estimate of people diagnosed with MS is 2.1 million.

Dr. Gow’s study will involve developing a mouse model of sensory and cognitive deficits for multiple sclerosis. While the physical disabilities associated with relapsing/remitting and chronic phases of MS have been characterized in detail, medical researchers don’t yet know as much about the other effects of the condition that affect the day-to-day quality of life of patients, including the inability of patients to remember lists of items and problems with simple arithmetic. Patients, Dr. Gow said, also develop problems with vision or engaging in conversations in noisy rooms. The animal model will facilitate the study of these issues, particularly hearing-associated tasks.

More than half of all MS patients experience cognitive and learning deficits, memory loss, and vision and hearing difficulties, Dr. Gow said. Studies to date suggest the symptoms stem from demyelinating-remyelinating lesions in the brain, which may block or slow signals. In effect, the thinning of the myelin sheaths may cause signals from the brain to “leak” from their conduit while being transmitted.

Dr. Gow will develop a “knockout” mouse model that will contain abnormalities in central nervous system myelin sheaths that mimic MS conditions. He will then utilize a number of electrophysiological tests to determine the effects of the dysfunctional myelin in hearing difficulties and cognitive deficits. Positively identifying any myelin-related causes contributing to such problems could lead to a list of new drugs to reduce their severity in MS patients.