The hunt for a defense against multiple sclerosis
Dr. Shalina Ousman follows a line of evidence that may lead to understanding the body’s own healing responses to MS.
Story by Julie Sedivy/Illustration by Julie Morstad
Listening to Dr. Shalina Ousman describe her research program is a bit like hearing a detective unravel complex evidence. She spends her research life patiently following the evidence of one scientific thread that she hopes may lead to new treatments for multiple sclerosis (MS) patients. Her thread begins with the observation that, when the disease strikes, the body tries to mount a defense. For MS patients, the body’s protective mechanisms can’t overcome the disease, and Dr. Ousman hopes that understanding why this happens could ultimately lead to harnessing the body’s own healing responses to help treat MS.
MS is an enigmatic disease with no known cause or cure. However, researchers do know that MS causes the body’s immune system to attack the protective sheath of neurons. This sheath protects the long fibers that nerve cells use to send signals to each other. The loss of this protective covering affects the ability of nerve cells to communicate, wreaking havoc on muscle function, coordination, bodily sensation, vision, speech, and bowel and bladder function.
Previous research showed that the activity levels of several genes were higher in the brains of MS patients than in healthy individuals. One of these genes, which produces a protein called alphaB-crystallin, piqued Dr. Ousman’s curiosity. After surveying the existing research literature, she suspected that alphaB-crystallin might play a role in the body’s defense system. One of the protein’s known functions is to prevent the clustering of other proteins in the eye that may cause cataract formation. It also prevents cells from dying and plays a role in preventing brain toxicity.
Based on what she found in the literature, she studied mice that couldn’t make alphaB-crystallin normally and had an animal form of MS. She found that these mice had greater movement problems when compared to mice that could express alphaB-crystallin normally. She also found that their immune cells were more active, possibly causing greater damage to their nervous systems, and that certain brain cells were more likely to die. These findings supported the idea that alphaB-crystallin was involved in keeping some of the effects of the disease at bay.
This led her to wonder why, if alphaB-crystallin was elevated in MS patients, it was not able to overcome the disease. One possibility was that the immune systems of MS patients also produce specific antibodies that target alphaB-crystallin, reducing the protein’s potential to combat the illness. An analysis of the blood of MS patients showed an elevated concentration of such antibodies, which supported this possibility.
If alphaB-crystallin was being attacked by antibodies in MS patients, then the next step was to see if injecting alphaB-crystallin into animals with the disease would improve their symptoms; indeed, they improved dramatically. Moreover, there was a decrease in the activation of immune cells in these animals, as well as signs that fewer immune cells were crossing over into the brain, resulting in less inflammation.
Dr. Ousman’s next steps are to understand exactly how higher levels of alphaB-crystallin can lead to improved outcomes, and to see whether these improvements will also occur in humans. Dr. Ousman is now conducting a study focused on isolating the immune cells from the blood of MS patients and studying the response of these isolated cells to alphaB-crystallin. Although the results are very preliminary at this point, she reports that they are intriguing.
It is unlikely there is a “silver bullet” treatment that will work for all MS patients, cautions Dr. Ousman. The disease is notoriously variable and tends to change in nature over a patient’s lifetime—a treatment that worked well at one point in time might stop working at another. However, Dr. Ousman emphasizes that incremental progress is being made: 15 years ago, nothing was available to help slow down the progress of MS; now there are 11 therapies. Perhaps Dr. Ousman’s detective work will eventually lead to more.