PORTLAND, OR (Ivanhoe Newswire) - More than 400,000 Americans are living with multiple sclerosis. It's a chronic, unpredictable disease that attacks the central nervous system. Now, new discoveries could help scientists come up with better treatments for the disease, even prevent its onset.
Whether parachuting, fishing, or enjoying the beach, Susan Dobrof has always pictured herself as an outdoors woman.
"It's like being in touch with God," Susan told Ivanhoe.
Not even multiple sclerosis could dampen her active lifestyle. Two years after being diagnosed she started law school.
"I realized, you know, you've been thinking about going to law school for a long time so you got to do it sooner rather than later," Susan said.
But ten years after her diagnosis, Susan began to lose her ability to walk. Eventually, her legal career came to a gridding halt too.
"Lawyers don't need to walk and run in order to practice law but we do have to think," Susan said.
Now Japanese macaques could hold the key to helping people like Susan. Scientists at the Oregon National Primate Center have discovered a new herpes virus in monkeys that causes an MS like disease in macaques. The brain lesions found are a classic indicator of inflammation in people with MS. The discovery could help scientists solve how the disease develops and stop its onset.
"That's the ultimate goal," Scott W. Wong, Ph.D., a professor and senior scientist at the Vaccine and Gene Therapy Institute at the Oregon Health & Science University and Oregon National Primate Research Center said. "It's a huge finding."
From monkeys to medication, a new drug called Ocrelizumab is also showing promise in treating MS. In preliminary studies, the antibody drug reduced the amount of brain lesions in patients. Findings that could one day help people like Susan stay active.
An active ingredient found in saffron, called crocin, could also help MS patients. Researchers at the University of Alberta studied the ingredient and found it could help protect brain cells from being damaged. It could be a couple of years before crocin is used in MS clinical trials.
RESEARCH SUMMARY
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease that affects the brain and spinal cord (central nervous system). More than 400,000 Americans are suffer from MS. The disease is caused by damage to the protective covering that surrounds nerve cells, called the myelin sheath. When these nerve cells are damaged it causes nerve signals to slow down or stop completely. The nerve damage is usually caused by inflammation that occurs when the body's own immune cells attack the nervous system occurring in any area of the spinal cord, brain, and optic nerve. So far the cause of this disease is unknown, but commonly it is thought to happen because of either a virus or gene defect. People who have a family history of MS or live in an area where MS is more common might be more likely to develop this disease.
SYMPTOMS: As with many diseases, symptoms vary due to the severity of each attack. Episodes may last days, weeks, or months and are usually followed with a remission. Because nerves in any part of the brain or spinal cord may be damaged, patients with multiple sclerosis can have symptoms in many parts of the body.
- Muscle symptoms: tremor in one or more arms or legs, weakness in one or more arms or legs, problems walking, problems moving arms or legs, numbness or abnormal sensation in any area, muscle spasms, loss of balance, and problems with coordination and making small movements.
- Bowel and bladder symptoms: constipation and stool leakage, urine leakage, strong urge to urinate, frequent need to urinate, and difficulty beginning to urinate.
- Eye symptoms: double vision, vision loss (usually only one eye at a time), eye discomfort, uncontrollable rapid eye movements.
- Numbness, tingling, or pain: Painful muscle spasms, facial pain, tingling, crawling, or burning feeling in the arms and legs.
- Other brain and nerve symptoms: Decreased attention span, poor judgment, and memory loss; depression or feelings of sadness, hearing loss, and dizziness (Source: www.ncbi.nlm.nih.gov)
NEW RESEARCH: So far there is not a known cure for MS. There are available medications and therapies to control symptoms, but the most recent discovery was found by the Oregon National Primate Research Center. They found that a natural disease in Japanese macaque monkeys (called Japanese macaque encephalomyelitis) is very similar to multiple sclerosis in humans. From 1986 through 2010, 56 monkeys at the research center developed paralysis in their legs and had to be euthanized. Later the researchers performed MRI scans on eight of them and they found that the MS-like disease caused the paralysis. The disease in the monkeys is very similar to a herpes virus. Researchers believe that a type of herpes virus could actually trigger MS in patients who have the disease in there genetics. Understanding how the herpes virus causes the disease similar to MS will give new important knowledge to developing more effective treatments for the disease or new methods to prevent the disease (Source: www.ohsu.edu).
OCRELIZUMAB: One characteristic of MS is inflammation, which takes the form of brain lesions. Ocrelizumab is a new antibody drug that has been proven to reduce the amount of brain lesions in MS patients. The drug successfully targets B cells, immune cells implicated in multiple sclerosis. B cells are now believed to drive the abnormal immune response in MS patients. An international multi-center study (79 centers in 20 countries) was conducted on 218 patients aged 18-55 years with relapsing-remitting multiple sclerosis and were split into 4 different groups. One group of 54 patients received placebo. The second and third groups of 54 received low and high doses of ocrelizumab. The fourth received the standard once-weekly treatment of intramuscular interferon beta-1a. After 24 weeks researchers found the number of active lesions was 89 percent lower in the ocrelizumab low-dose group and 96 percent lower in the high-dose group compared with the placebo group. The study showed that the drug rapidly reduced brain lesions in MS patients and could lead to fewer relapse.
INTERVIEW
Dr. Scott W. Wong, Senior Scientist at the Vaccine and Gene Therapy Institute, Division of Pathobiology and Immunology, Oregon National Primate Research Center, and Professor of OHSU School of Medicine discusses viruses
Tell me about this discovery for MS.
Dr. Wong: It's actually pretty exciting, we've found in the colony of Japanese macaques here at the primate center that some animals started to develop the disease manifestation, referred to as Japanese macaque encephalomyelitis in the mid 1980's that looked very similar clinically to Multiple Sclerosis in humans. And then when we did further analysis of these animals we found that when we looked at their brain structures they had areas of demyelination occurring and that's very similar to what happens in Multiple Sclerosis patients.
What exactly do you think you've found?
Dr. Wong: We're very excited; we found a novel herpes virus associated with one of the lesions. So when we took a lesion out at necropsy when the animal was euthanized we put that lesion in cell culture and found that a virus came out of that particular lesion. So this was the first isolation of a virus from a lesion. We've subsequently been able to identify or isolate that virus in similar lesions from animals.
So what does that mean for humans?
Dr. Wong: It's a huge finding, for years medical researchers have thought that Multiple Sclerosis is associated with an infectious agent and it's been thought to be a human herpes virus. Human herpes virus 6 and Epstein Barr virus have both been postulated to be associated with MS and there is good evidence to suggest that Epstein Barr virus may be associated with MS. Interestingly, the virus that we identified is similar to Epstein Barr virus but it's slightly different. So it's a monkey homolog of a different herpes virus that's related to Epstein Barr virus.
Are we close to a cure for MS?
Dr. Wong: Well that's a good question. What we are hoping to do is to start with the data that we have with the monkey virus to see if there is a similar virus in humans that have MS. So one, we can start getting patient samples and try to see if we can identify that particular virus. If so then we may have new targets to attack the agent that may precipitate Multiple Sclerosis in humans.
So you've found a new virus in the monkeys and you're trying to figure out if this same virus is in humans? If it is then you may be able to find new treatments and or a cure for this illness?
Dr. Wong: Absolutely. That's the ultimate goal is to see if we can identify a similar infectious agent and see if we can look at its genetic material and find its weak points so we can target therapies against that. That's a tall order and there's a lot of research associated with this that's going to have to go forward but it gives us a better handle on what may be an infectious agent or etiology associated with the disease. Now if a virus cannot be found the animal model that we've been able to develop will also be valuable because it's a spontaneous demyelinating disease in this colony of Japanese macaques. And that's the first non human primate model of Multiple Sclerosis. So if we can better understand how the disease precipitates in these animals or initiates we may have a better understanding of what the underlying causes or factors that is associated with Multiple Sclerosis in humans.
Where are we in that process?
Dr. Wong: With the animal model we're just starting to better tease it apart. We've been studying it for quite a few years, we had our first publication in July and it describes the model. There's a lot of interest in the animal model but again there's a lot of work left to do.
How similar are the Japanese macaques to humans?
Dr. Wong: Well the monkeys on the ancestral tree they're very similar. Obviously we have the great apes, the chimpanzees and gorillas, the chimpanzees being the most related to humans and the Macaques are further down the tree. But having a non human primate that can develop disease like the Japanese Macaques do is very significant. Because just like you said they are much more related to a human than a rodent is. So we have a better chance of understanding how the disease process works.
Are there any formal studies out to check out the model in humans?
Dr. Wong: We're collaborating with some clinicians at OHSU to obtain patient samples and we're collaborating with a number of investigators there also with advanced MRI imaging center to look at the high resolution structures of the brain in our animals and compare those to humans to see if we can better quantify the disease process. So there's still a lot to do.
Is this your life's work, is MS a special interest for you?
Dr. Wong: Fortunately for my family we don't have any disease in our family. However, I met MS patients when I was in my teens at the Veterans Hospital and saw first hand how devastating the disease is. My interest stems from being a virologist. We've developed another animal model here at our primate center; obviously everybody is familiar with AIDS. The first disease that was an indicator of AIDS was a lesion called Kaposi's sarcoma (KS) you may be familiar with that. It was a purple lesion on the skin of AIDS patients. They found in 1995 that, KS was associated with a human herpes virus. In fact it was a newly identified herpes virus. So we have an animal model here in our Macaque colony where we study SIV which is the monkey version of AIDS. And this simian herpes virus that we have identified can induce malignancies in SIV infected monkeys. So now we have another virus that we can better understand how viruses associate with cancer in immune suppressed individuals. So we're developing this as an animal model. So my work for years has been associated with that herpes virus. And now we've spun off in to the MS field.
So this could be medicines next big thing?
Dr. Wong: We're hoping that we can develop this in to two things. One, obviously if we can identify a similar virus in humans associated with MS. And two, to show that this animal model closely parallels Multiple Sclerosis in humans so that again we can use this animal model to evaluate therapeutic agents to help treat MS patients.
Can you tell how you came over this?
Dr. Wong: This disease was identified in 1986. Our pathologist here at our center euthanized the animal and looked at the brain of the infected monkey and found that, the animal's brain had demyelinating lesions very similar to what Multiple Sclerosis patients suffer from. So demyelination means that the myelin sheath around the neurons is destroyed. And when that insulation is gone the neurons start to die and that's what happens in Multiple Sclerosis patients. And that was what we found with the Japanese Macaques that were affected with the disease. So since 1986 to the present we've collected a number of animal samples now where we're better able to look at the disease and better understand how the disease process is similar to Multiple Sclerosis.
FOR MORE INFORMATION, PLEASE CONTACT:
Jim Newman
OHSU Strategic Communications
(503) 494-8231
newmanj@ohsu.edu
