Solving the Mystery of MS

 

You’re young, healthy, with endless possibilities ahead—love, career, family. And then…

Something odd happens. Your body refuses to do what it’s always done. Maybe your left leg gives way suddenly. Or your right arm tingles and becomes weak. Or you can’t see out of one eye.

What could be wrong?

Your doctor orders an MRI image of your brain and spinal cord, finds telltale scars known as lesions—damage to your central nervous system—and delivers the diagnosis. You have multiple sclerosis (MS), an incurable disease that might one day disable you.

What happens to all your plans for the future now?

WHEN your immune system is doing its job properly, it defends you against viruses, bacteria, and other microscopic invaders. But if you have MS, some of the immune system’s warrior cells get confused, and decide that your neurons (brain and spinal cord cells) are enemy invaders. They throw everything they have at the “enemy.” They strip the protective myelin coating from axons, the neurons’ information conductors. That interrupts the cells’ ability to send signals to the rest of your body. Muscles, joints, eyes, thought processes—all require clear signals in order to function well.

Across Europe, MS afflicts approximately 630,000 people, according to the World Health Organization. The disease affects about twice as many women as men, and typically strikes in the late 20s or early 30s. You’re more likely to get MS if a parent or sibling has it, but “It’s not a genetic disease in the strict sense,” says Professor Reinhard Hohlfeld of the Institute of Clinical Neuroimmunology in Munich, Germany. Many different genes play roles in the condition, and MS requires some sort of trigger or combination of triggers to set the process in motion.

IT’S NOT always an easy illness to diagnose. “There are no two persons with the same kind of disease presentation and symptoms,” says neurologist Dr. Marie D’Hooge of the National Center for Multiple Sclerosis in Melsbroek, Belgium. Depending upon the area of the nervous system affected, initial symptoms could include loss of bladder control; balance problems. Learning, short-term memory and concentration problems are common in MS, according to the National Multiple Sclerosis Society-US. But unlike Alzheimer’s, the disease rarely affects long-term memory, general intelligence, or reading comprehension.

The form MS most often takes at the onset is known as Relapsing Remitting (RRMS). Symptoms usually appear without warning, then either completely or almost completely disappear on their own—even if not treated—in days or weeks. But they leave behind damage.

Most with RRMS (about 80 percent) will eventually advance to Secondary Progressive MS (SPMS), although it may take 25 or more years: no more relapses, just a slow, steady decline that could eventually be completely disabling.

Another type, Primary Progressive MS (PPMS) affects about ten percent of those with MS and usually strikes after 40. Instead of relapses and remissions, symptoms slowly get worse. While RRMS typically affects the brain, most with PPMS “show symptoms which reflect significant involvement of the spinal cord,” says Dr. Regina Schlaeger, a neurologist and MS researcher with the University Hospital Basel, Switzerland. As a result, those with PPMS often have problems with their legs.

ONCE the massive inflammation of a relapse has been extinguished with corticosteroids, the first line treatments prescribed to limit further relapses are inteferon drugs or glatiramer acetate (Copaxone).

But these drugs put the brakes on the immune system as a whole. And a well-functioning immune system is essential to health. So, the goal of the newer lab-produced monoclonal antibody drugs, much like the goal of our own natural antibodies, is to target more precisely cells that cause disease. Dr. Coetzee of the US National Multiple Sclerosis Society dubs monoclonal antibodies “smart bombs” thanks to their ability to “wipe out the immune cells that are bad, but leave the rest.”

The most recently approved monoclonal antibody for MS, alemtuzumab (Lemtrada), is actually a repurposed drug, developed in the 1980s to treat a type of leukemia. Clinical trials showed that alemtuzumab reduced both the number of relapses and the extent of brain lesions in early RRMS.

Three new oral drugs—Fingolimod (Gilenya), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera) —are now available. Prior to their approval, all MS medications had to be injected.

Some may have to wait for the latest treatments, however. “Availability of medications is very variable worldwide,” says Professor NAME Thompson of the MS International Federation. He says access is limited in some Eastern European countries.

There are no drugs approved specifically for Secondary and Primary Progressive MS, and those used for RRMS don’t work against progressive disease, although anecdotal evidence suggests that their use  during the RRMS phase may delay or prevent later progression.

Physiotherapy is among the most effective treatments at the progressive stage, says Professor Thompson. Although targeted to the affected areas, it’s “not just about focusing on muscle,” he says. “There’s actually evidence of influencing how the brain responds to damage.” Working the body, in other words, might coax the brain into self-repair.

SOON doctors may have yet another “smart bomb” in their arsenal, but with an important difference. The new monoclonal antibody, known only as rHIgM22, is the first that appears capable of rebuilding the neurons’ protective myelin coating. That means rHIgM22 might be able to halt or even reverse damage in the progressive phase. It is currently in clinical trials.

Often, a breakthrough in treatment comes not from a new drug, but from a remedy developed for a different disease, used in a new way.

In one recent study (The Lancet, March 2014) statins, originally developed to lower cholesterol, dialed back both nervous system damage and disability in secondary progressive MS.  And a study in the journal Neurology (March 2014) suggests that cannabinoids—compounds found in the marijuana plant—can help rebuild the protective myelin coating on a neuron’s axons, potentially offering a new treatment for Secondary and Primary Progressive MS.

Women have long reported suffering fewer relapses during pregnancy, prompting UCLA researchers to administer estriol, a hormone that’s abundant during pregnancy, together with glatiramer acetate to non-pregnant women with RRMS. In this just-reported study, the women taking estriol had 47 percent fewer relapses than those who got glatiramer acetate and placebo, and also scored higher on cognitive tests. Estriol is widely prescribed for menopausal symptoms.

And researchers like Dr. Emmanuelle Waubant, professor of neurology and pediatrics at the University of California at San Francisco MS Center, are puzzling out why some get MS while others escape it. Dr. Waubant found that though exposure to some common viruses appears to increase risk, exposure to others might actually lower it.  But that doesn’t tell the full story.

“There are probably interactions between the genes one has, the type of viruses one acquires, and what time you acquire those infections,” says Dr. Waubant.  In other words, it’s not just which genes and viruses combine that appears to increase or decrease risk. When they combine might be just as important to determining your risk of MS. Understanding these complex interactions may help researchers develop strategies for treatment and prevention.

YOU CAN help manage MS yourself. It tends to be more prevalent in countries where people get less sun exposure, and being deficient in vitamin D (produced in the body in response to sunshine) increases the risk of getting the condition. Dr. Marie D’Hooghe recommends monitoring vitamin D levels, especially in winter. If blood tests detect a deficiency, supplementing with 900 to 1000 I.U. of vitamin D a day might help reduce relapses.

The simplest measures might be the most important. Although MS’s course is unpredictable, several experts say you’re likely to increase your odds for better outcomes by living a healthier lifestyle. If you now smoke, stop; smoking both increases the risk of getting MS and speeds up its progression. Eat healthful foods. Reduce stress. And stay active.

Many of the experts interviewed for this article believe we’re on the brink of new therapies to limit progression and potentially reverse it.

“In the span of almost 20 years, we’ve seen this disease go from having no treatment options available to having ten to 12 treatments for relapsing remitting MS, which is a remarkable turn of events,” says Dr. Coetzee.

There’s a concerted focus among neuroscientists around the globe on finding treatments, especially for progressive MS. With the drugs recently approved, and others coming through the pipeline, there are good options for managing it today—and real hope for beating it tomorrow.

YOU CAN help manage MS yourself. It tends to be more prevalent in countries where people get less sun exposure, and being deficient in vitamin D (produced in the body in response to sunshine) increases the risk of getting the condition. Dr. Marie D’Hooghe recommends monitoring vitamin D levels, especially in winter. If blood tests detect a deficiency, supplementing with 900 to 1000 I.U. of vitamin D a day might help reduce relapses.