September 10, 2013- Human remyelination study in MS launched at WSU and DMC Harper University Hospital
A groundbreaking study in multiple sclerosis focusing on “remyelination in the brain” has been initiated by Omar Khan, M.D., professor and chair of neurology at the Wayne State University School of Medicine.
"This is a novel approach in the treatment of multiple sclerosis, which is characterized by diffuse demyelination and axonal loss in the central nervous system,” said Dr. Khan, who also serves as director of the Multiple Sclerosis Center and director of the Sastry Foundation Advanced Imaging Laboratory. “In this study, we are targeting remyelination in the central nervous system.”
Dr. Khan noted that there are 10 United States Food and Drug Administration-approved treatments for multiple sclerosis, none with any well-characterized reparative or remyelinating potential. Those treatments primarily focus on altering the behavior of the immune system and target inflammation.
However, this new approach targets remyelination in the central nervous system using a humanized monoclonal antibody that binds to the semaphorin 4D, a member of the semaphorin family of proteins and an important mediator of axonal growth cone guidance. Semaphorin-induced signaling also has been shown to induce growth cone collapse of neurons and apoptosis of neural precursors, and to induce process extension collapse and apoptosis of oligodendrocytes. Semaphorins consist of a family of soluble and membrane-bound proteins that were originally defined as axonal-guidance factors. These proteins play important roles in establishing precise connections between neurons and their appropriate targets.
“Therefore, it is a plausible target with the realistic goal of achieving remyelination,” Dr. Khan said. “This is a paradigm shift and the start of the next generation of therapies to treat multiple sclerosis that will change its focus to repair rather than inflammation.”
The brain can largely be divided into gray and white areas. Neurons are located in the gray area, and the white parts are where neurons send their axons – similar to electrical cables carrying messages – to communicate with other neurons and bring messages from the brain to muscles. The white parts of the brain are white because a cell type called oligodendrocytes makes a cholesterol-rich membrane called myelin that coats the axons. The myelin’s function is to insulate the axons, similar to the plastic sheath coating electrical cables. In addition, the myelin speeds communication along axons and makes that communication more reliable. In patients with MS, their immune system attacks the myelin sheathing. The subsequent degradation leads to the messages from the brain to other parts of the body leaking and derailing from their intended target.
Restoring the myelin sheathing is the goal of Dr. Khan’s new study.
The Wayne State University Multiple Sclerosis Center, in collaboration with Vaccinex, a privately-held biotechnology company headquartered in Rochester, N.Y., initiated this early stage dose-defining study, monitored by the FDA.
“If successful, this will lead to large scale studies with this molecule targeting remyelination in the brain as a primary focus, detected by advanced imaging techniques such as magnetization transfer ratio,” Dr. Khan said. “The real challenge will be to reverse or reduce conduction blocks in the demyelinated nerve that may translate into neurologic improvement. If we could achieve that with this approach, it opens the door for hundreds of thousands of multiple sclerosis patients for whom no therapy is currently effective. This may also provide a unique opportunity in combining therapies with different mechanistic approaches.”
WSU is home to the only MS center in Michigan and among the 10 sites in the world undertaking this translational initiative. The center is among the top five MS centers in the U. S., with more than 4,000 patients. The center is involved in cutting-edge immunologic, genetic, MR imaging and therapeutic studies.
Dr. Khan said only three molecules in the world, including this monoclonal antibody, are being investigated in patients with multiple sclerosis that focus on remyelination.
“It is humbling to lead such a unique groundbreaking effort and that Wayne State University is one of the few centers in the world that are participating in this next true generation translational research,” he said. “The patients are observed over night at Harper University Hospital, which has been a great partner in facilitating this research endeavor.”
Multiple sclerosis affects more than 500,000 people (or one in 600) in the U.S. and more than 2 million worldwide. After trauma, it is the most common cause of disability in young adults. While there is no cure, several treatments are approved for the relapsing form of multiple sclerosis that reduces the frequency of flare-ups and slows disease progression.
For further information regarding the Wayne State University Multiple Sclerosis Center and this study, call 313-745-7186. To make an appointment with the neurologists of the Wayne State University Physician Group specializing in multiple sclerosis, call 313-745-4275.
WHAT IS H1N1 INFLUENZA?
H1N1 influenza is a respiratory disease that is caused by a type A influenza virus. The current H1N1 virus contains unique genes from pig and human influenza viruses and hence is called the “Novel H1N1 Influenza Virus”. This strain of flu germ spreads from human to human and can cause illness.
Does H1N1 INFLUENZA pose special risks for pregnant women?
Pregnant women are at an increased risk of catching H1N1 or seasonal flu. Pregnant patients with H1N1 infection have an increased risk of complications. Although influenza viruses do not infect the baby while in the uterus, the high fever and any complications caused by the flu can potentially be harmful to the baby.
WHAT PRECAUTIONS CAN I TAKE TO PROTECT MYSELF AND MY UNBORN BABY?
The best way to protect yourself and your unborn baby is to have a vaccination (which is safe during pregnancy). You should also make sure you follow good hygiene practices including:
- Wash your hands often with soap and warm water. Alcohol-based gel hand cleaners are also good to use.
- Try to avoid close contact with sick people.
- Talk to your doctor about your concerns.
WHAT ARE THE SYMPTOMS OF H1N1 INFLUENZA?
The symptoms of H1N1 flu are similar to the symptoms of seasonal flu and may include acute onset of:
- Fever (greater than 100 F or 37.8 C)
- Sore Throat
- Stuffy nose
- Some people have reported diarrhea and vomiting associated with H1N1 flu.
WILL THE SYMPTOMS BE THE SAME IF I AM PREGNANT?
Yes, the symptoms of flu will be the same as in women who are not pregnant.
WHAT SHOULD I DO IF I GET SICK?
If you get sick with flu-like symptoms, stay home, limit contact with others, and call your doctor as soon as possible.
- Treat any fever right away. Tylenol® (acetaminophen) is the best treatment of fever in pregnancy.
- Get plenty of rest and drink clear fluids.
- Your doctor may test you for flu or will decide if you need medications to treat the flu.
- Cover your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the trash and cleanse your hands.
- Clean hands often with soap and water or alcohol- based hand rub.
- Do not go to work, school, or other public places while you are ill.
- Avoid close contact with other people.
- Get emergency medical care right away if you have trouble breathing, chest pain, purple or blue lips or skin, severe vomiting and are dehydrated and/or dizzy, unresponsive or confused.
IS IT OK TO BREAST FEED MY BABY IF I AM SICK?
- Do not stop breastfeeding if you are ill. This will help protect your baby from infection.
- Be careful not to cough or sneeze in the baby’s face, wash your hands often.
- Your doctor might ask you to wear a mask to keep from spreading this new virus to your baby.
- If you are too sick to breastfeed, pump and have someone give the expressed milk to your baby.
IS THERE A VACCINE FOR H1N1 INFLUENZA?
Yes, an H1N1 virus vaccine is expected to be available in mid- to late October 2009. The CDC recommends this vaccine for pregnant women when it first becomes available. This vaccine has been tested in pregnant women and found to be safe and effective.
REMEMBER: The seasonal flu vaccine is not expected to protect against the H1N1 flu, therefore individuals are encouraged to get both types of vaccines.