The bad manners of MS

How does MS work? What is happening to make my arm go numb, my vision become cloudy, or my bladder ignore my commands? Unfortunately, pathogenesis—the manner of how a disease develops—remains a mystery with MS. A mystery worth every hour we as researchers can give it.

“Multiple Sclerosis” is an old term, and it’s simple. It means many (multiple) areas of scarring (sclerosis). The areas of scarring, unfortunately, happen to be in the brain and spinal cord (central nervous system or 

​CNS). The kidney or liver or bones can handle some scarring and retain normal function. The central nervous system is less resilient so the norm here for patients with MS is partial recovery of function or no recovery at all.
 
In a close up, what do these scarred areas look like? To quote Claudia Luchinetti, a Mayo Clinic neurologist, the pathologic hallmark of MS is the appearance of “seas of macrophages” within lesions. Lesions are areas damaged by disease. Macrophages are immune cells that are drawn into areas of damage. They fight to eliminate the threat and clean up the damage. The conventional thinking about MS holds that 1) the body’s innate autoimmune process (still largely a mystery), 2) causes the macrophages to come in and 3) damage the brain. Another possibility is that these many macrophages are just doing their job, killing the invaders, and that brain and spinal tissue get injured as “collateral damage.”
 
I now think of MS as a train derailment, thanks to a leading Canadian professor who spoke at a recent MS meeting. Imagine that you are an alien with no preconceived notions about life on Earth, and you’re observing from your spaceship above. There is a train derailment and the train cars overturn and jump off the track. Passengers are hurt or killed. Within a short time, a “sea” of orange and yellow-jacketed responders arrives on the scene. They swarm the damaged and now stationary train, inside and out. But as an alien, you don’t really know if the orange jackets are doing good or evil. They could be finishing off the stricken passengers. Or, in the alternative, perhaps they are there to help. Of course, we Earthlings understand that the jacketed ones are first responders, stabilizing the situation, helping the injured, preventing further injuries and loss of life. But we know that only because we understand that a train derailment is an unusual and unwanted event. That is, we understand the cause of the problem, and we welcome its remedy. No one in their right mind would try to hinder the important work of the emergency workers. (Except perhaps a misguided alien with no concept of life on Earth.)

This train derailment scenario sheds light on our scientific work with MS, where we don’t understand the cause but we can see the aftermath. That aftermath is an influx of lymphocytes and macrophages, effector cells of the immune system. Their work results in “demyelination” where myelin is lost, and the insulation on the wires of our nerve cells (axons) vanishes, causing microscopic short circuits. These short circuits lead to neurologic dysfunction and sometimes other debilitating symptoms. We do know this: The symptoms depend on the anatomic location of the train wreck.
 
The field of MS study embraces so many questions: What are the inciting events that lead to demyelination? Are the infiltrating macrophages and lymphocytes leading to the tissue damage or are they limiting it? And, while we’re at it, is demyelination the root cause of the disease or is the cause the result of something else, like an infection or another autoimmune process?
 
I, for one, want to crack the bad manners of MS. To truly understand the pathogenesis, I try to take a broad if not alien view of the disease. I know that demyelination is not exclusive to multiple sclerosis; other conditions trigger it as well. Influenza viruses occasionally get into the brain and cause widespread demyelination. The lowly JC virus also produces demyelination, usually in persons with a very impaired immune system (such as people with AIDS and the elderly). And demyelination of nerve cells does not stop at humans. The distemper virus that infects dogs causes demyelination and severe neurologic disease. These well-known examples of infections that lead to demyelination pull my view of MS way back.
 
To me, as a researcher with three decades of experience, it makes sense to take a broad view, an inclusive view, and examine demyelination as an effect of something else. I believe that this enquiry will help us find both the cause and the remedy. 

Image credits: ID 68543427 © Pavlo Syvak | Dreamstime.com