A new meta-analysis by Dr. Angélique Corthals proposes that much of the difficulty we have with understanding the causes of MS may be because we're wrong about its basic mechanism. In a publication in The Quarterly Review of Biology, she proposes that rather than an autoimmune disease like previously supposed, MS might in fact be a metabolic one with an immune component. 

It's a bold assertion to be sure, and one without original data to back it up (at this point, anyway). With MS, the myelin which protects and insulated the nerve tissue on your brain and spinal cord swells, and then scars, leading to neuronal damage. Corthals' theory gives another framework to approach this damage, and one with links to a disease we do understand — atherosclerosis. This is where things get a
bit dense, so bear with me.

There are certain environmental and genetic factors which can impair PPARs (peroxisome proliferatoractivated receptors), which is part of the system that controls the metabolism of fat as well as immune response. When it's running at partial power, the PPARs can't properly control the levels of LDL — the infamous bad cholesterol — which leads to a build up of an oxidized toxic derivative of LDL called oxLDL in the blood. Once these are in the system, Corthals believes the body is "primed" for MS, and it can be triggered by a number of causes, including Epstein-Barr Virus, which is linked to MS in its own right.

Once triggered, an immune system chain reaction starts. The body sends out macrophages to deal with a pathogen, but the macrophages incorrectly gorge themselves on oxLDL. This puts them in a "zombie state", where they don't die and can't empty their contents, instead just building up plaques which damage the myelin sheath, and cause the symptoms of MS.

Edited to clarify: At this point, the disease triggers the immune problems we know of as MS. The theory isn't discarding the immunological side of the disease, just citing metabolism as a root trigger, which leads to the problems of the immune response.
Said Corthals: Eventually, the toxic macrophages are cleared, leading to the remission part of the RRMS (relapsing-remitting MS) cycle. But this detente holds only until the next trigger comes along. Dysfunction of the PPAR is further implicated in MS because it slows the repair mechanism of the central nervous system to a crawl, preventing the efficient renewal and synthesis of myelin.

It's a novel theory, and while Corthals is working on pulling together some empirical data to back it up, it does answer some of the issues with how MS manifests. The disease has been linked previously to low levels of vitamin D, and is on the uptick in recent decades. Low vitamin D and a diet high in both saturated fat and carbohydrates (which is likewise on the rise) both contribute to the impairment of PPARs.

The mechanism that Corthals suggests is also interesting because it's incredibly similar to that of atherosclerosis. Atherosclerosis is when PPAR failure causes plaque buildup and scarring in arteries, which is the equivalent to what's being described happening to myelin. Also interestingly, men are far more likely to have atherosclerosis and women to have MS, which Corthals suggests may be because of the different way sexes metabolize fats. In the paper, she recommends "multiple sclerosis should be thought of as a metabolic disease, the female equivalent of atherosclerosis, not as a disease of the immune system."

If the raw data bears out this theory, it would mean a radically different approach to the treatment of a major chronic disease. One based on lipid metabolism (and potentially diet) rather than targeting the immune system directly. If it holds up, it would be a major paradigm shift in the way MS is handled — but first we need to see if the data fits the theory.

This effectively creates a ''disease in a dish'' that can be replicated and studied by researchers who have previously had only blood cells, autopsy tissue and cerebrospinal fluid to work on. The cells also mean scientists can avoid using human embryos, overcoming ethical concerns.

Professor Bernard said this would create a limitless supply of the cells for researchers to study the mechanisms of the disease and to test new drugs.

''Much research to date has relied on animal models that, while similar to MS, have been very different to the human disease, which has led to ineffective and even detrimental MS treatments,'' he said. MS is the most common chronic neurological disease in the world and affects about 21,000 Australians.

Given there is no cure and treatments work for only about 30 per cent of sufferers, Professor Bernard said it was critical to continue the research. ''There are so many people suffering from this difficult disease and it costs Australia about $2 billion a year.''

​The findings were published in Stem Cell Research. 

The prime of her life
In 2002, Levy was in her 30s and an active hiker and skier with a job on Wall Street and later in San Francisco, California. But her life took a turn when she started stumbling, falling down and dragging her right leg. Her doctor's diagnosis? Secondary Progressive Multiple Sclerosis, a less common form of MS and, as the name implies, one that usually plagues people with the disease after its initial course.

The National Multiple Sclerosis Society defines MS as a "chronic, often disabling disease that attacks the central nervous system, which is made up of the brain, spinal cord and optic nerves." Symptoms of MS include extreme fatigue, difficulty walking, problems with memory and heat sensitivity.

The most common form of MS is relapsing-remitting, in which people have acute attacks followed by periods of remission. In secondary progressive, however, the disease worsens steadily and there are no acute flare-ups. People with relapsing-remitting may later develop secondary progressive MS.

I was scared of being in a wheelchair. I was scared of getting worse and worse. I had traveled around the world before I got sick, I was super independent. --EJ Levy, MS patient

Levy says she lived in the same building as her parents at one point because she needed them to help take care of her. She says she mostly stayed at home, and when she did venture out she usually walked only a block or two with a cane. She relied on a wheelchair for longer distances.

She says she realized she would eventually be unable to walk. "I was scared of being in a wheelchair. I was scared of getting worse and worse. I had traveled around the world before I got sick, I was super independent," Levy says.

Trying things out
After exhausting the usual MS treatments -- and developing intolerable side effects -- Levy also became frustrated that the treatments were primarily designed for people with the more common course of the disease, and not the secondary progressive course.

evy's neurologist then discussed the possibility of trying 4-aminopyradine -- a version of the same drug the FDA approved Friday that was available only through compounding pharmacies. Just three days after taking the drug, Levy was able to walk unassisted.

"I never thought I could put my cane away for good," she said. Now she hopes the same drug that helped her will be able to help other people. She addressed an FDA advisory panel late last year and recommended approval of it. "It's about quality of life," Levy says.

How it works
Two phase III clinical trials of Ampyra showed 35 and 43 percent of patients experienced, on average, a consistent improvement in their walking speed, increasing it by about 25 percent. According to the National Multiple Sclerosis Society, even a modest improvement in walking ability could mean that thousands of people could benefit from the drug.

Dr. John Richert, executive vice president of Research & Clinical Programs at the National Multiple Sclerosis Society, says the drug can be used by most people with MS. However, the drug is not for people with a history of seizures or people who have moderate to severe kidney disease.

Richert says approval means patients can now skip the compounding pharmacy and get a consistent, exact dosage in a guaranteed time-released formula, which would lower the risk of getting a toxic dose instead of a therapeutic dose.

"It's likely that further study and clinical practice may help to determine the extent to which the drug may impact other functions, and may also provide hints as to which patients are most likely to respond positively to the therapy," Richert said.

He added that the drug would not help nerves that have been destroyed and emphasized that people should try the drug to see if it works for them.

Ampyra may not work for everyone. "Like any medication, people will have different responses, so they should talk to their doctors about whether it's appropriate to start therapy on Ampyra," according to a spokesperson from Acorda, Ampyra's manufacturer.

Moving with MS 
Today. Levy is doing well. She established the not-for-profit organization MS Hope for a Cure, and in three years the organization has raised $1.8 million for research and programs to help people living with MS.

​She has also completed several five-mile hikes. But she says she is always conscious of where she steps. She says she occasionally has some weakness in her leg, but that she is thankful for every day: "I don't ever take jumping out of bed for granted."

​Schneider spent the last 16 years climbing all seven of the continental summits, finishing with this six week trek to climb to the top of the world.

"Climbing Everest was something I had to prove to myself. I had to prove that I was still in charge of my physical body, at least for now with MS. I needed to push it to the limit and see how strong I was physically and to see how strong I was mentally."

Now, Schneider is booked to speak at the World MS Day conference in Stuttgart, Germany, and has been invited to speak in Spain, Holland, Austria, and Slovakia.

"To put a face to MS and give people with MS hope that their physical lives are not over. Of course, most people with MS are not able to climb mountains in their lives. Most people have difficulty walking across the room."

She wants people to know that it all takes one step at a time.