MS attacks the myelin sheath that protects axons | 3d4medical.com

Inside Scope: Michigan Medicine Health Syste-Wide

MS: One Disease or Two?
Research suggests need for individualized treatments

There are many mysteries surrounding multiple sclerosis, an unpredictable, degenerative disease that attacks the brain and spinal cord. Scientists don’t understand why symptoms progress more rapidly in certain patients, or why some patients respond better than others to drugs used to treat MS.

Benjamin Segal, M.D., has devoted his career as a researcher and a physician to finding better ways to help people with multiple sclerosis. Fascinated by how the central nervous system interacts with the immune system, Segal wants to understand the “why” of the body’s abnormal response, what cells are involved, how they get into the central nervous system and what factors they produce that cause damage — all to develop new, more effective treatments for the disease.

Since joining the Medical School faculty in 2007, Segal has already made progress toward this goal. He and his colleagues recently discovered that two immune system T-helper cells, called Th1 and Th17, triggered clinically indistinguishable symptoms in research mice with a form of MS.

Although their symptoms were the same, mice that were exposed to Th1 cells had different inflammatory agents in their central nervous system tissue than mice exposed to Th17 cells. The animals also responded differently to drugs intended to block the inflammatory response, suggesting there could be two different forms of multiple sclerosis. The research findings also might explain why some patients respond better to one medication than another — or don’t respond at all.

As director of the U-M’s new Multiple Sclerosis Center, Segal is all too familiar with the devastating effects MS can have on patients and their families.

“MS usually presents in young adults in their 20s and 30s,” says Segal, the Holtom-Garrett Family Professor of Neurology. “They face living with a chronic, disabling disease that they will have for the rest of their lives.” Segal also directs the Holtom-Garrett Program in Neuroimmunology.

Multiple sclerosis is believed to be an autoimmune disease that begins when cells in the body’s immune system attack the central nervous system (CNS), specifically proteins in the myelin sheath surrounding axons — long filaments extending from nerve cells. The immune system’s misguided attack disrupts the axons’ ability to relay electrical impulses from cell to cell, leading to symptoms that include vertigo, balance and vision problems, tremor, weakness, numbness, loss of bowel and bladder control, and cognitive difficulties.

In future studies, Segal hopes to learn how different T cells move from blood to the CNS and to devise strategies to block those pathways. “The more we understand, the more we can individualize therapies and make them more specific, so we don’t leave patients as vulnerable to side effects,” says Segal.

For patients, the Multiple Sclerosis Center means access to the newest therapies, as well as to specialists with extensive experience diagnosing and treating the disease over time, and staff attuned to patient needs. Patients often need many types of support from a variety of professionals, explains Segal — including speech, occupational and physical therapists, as well as psychological support.

“Ultimately we want to provide care under one roof from all health providers concerned with the diagnosis and treatment of MS patients,” he says.

Segal knows there is a lot of work to do, but he remains driven and optimistic. “To offer patients reasons for hope, and to intervene in the disease process to improve their quality of life, is what it’s all about.”
—KIMBERLEE ROTH

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Patient information on multiple sclerosis

 

Kathleen Collins | Martin Vloet, U-M Photo Services

HIV’s Secret Weapon

HIV, the virus that causes AIDS, is crafty and dangerous. Immune cells called cytotoxic T lymphocytes usually seek out and destroy cells infected by a virus, but HIV has a unique way of evading them. In recent research, U-M scientists led by Kathleen Collins, M.D., Ph.D., discovered how the virus uses an adaptable protein called Nef to short-circuit the body’s immune response.

Collins and her colleagues describe how Nef latches onto an important immune system molecule in infected cells — preventing it from moving to the cell’s surface where it could signal T lymphocytes to move in and kill the cell. This allows HIV to remain hidden and continue multiplying inside the cell.

“Anti-viral drugs protect new cells from infection, but have no effect on cells that are already infected and hidden from the immune system,” says Collins, an associate professor of internal medicine and of microbiology and immunology. She is now searching for new drug compounds capable of blocking Nef and targeting HIV inside infected cells. —SP

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Nano-Vaccine for Hepatitis B?

Animal tests of a new type of hepatitis B vaccine developed by scientists at the Michigan Nanotechnology Institute for Medicine and Biological Sciences indicate that the vaccine is non-toxic and generates a strong, sustained immune response. The vaccine uses a nanoemulsion-based nasal spray to deliver a current hepatitis B antigen, which activates the body’s immune defenses against the hepatitis B virus. Positive results from animal testing mean researchers may soon begin the first human clinical trial of the vaccine. —SP

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Gene Expression and Lung Cancer Survival

Research by Comprehensive Cancer Center scientists could one day help identify, in advance, patients with early-stage lung cancer who will need aggressive chemotherapy after surgery. Researchers identified genes active in 442 lung cancer tissue samples, and factored in clinical predictors like tumor stage, age and gender. They were able to divide the tumors into groups with better and worse survival outcomes, and hope this research will lead to diagnostic tools to help physicians determine individualized treatment plans for lung cancer patients. —SP

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