There's a lot of focus on developing drugs that inhibit or stop this neurodegeneration, which we believe is the underlying cause for difficulty walking, leading people to require a wheelchair.
Three years ago, Kristie Salerno Kent, a singer-songwriter, was standing in a security line at the airport on her way home from a gig when her legs went numb.
"From the waist down, it felt as though I was trying to walk through a bowl of oatmeal," said the 38-year-old musician, who has multiple sclerosis.
She inched her way to a security officer, who called for a wheelchair and helped remove her shoes and belt to get her through security. Frightened and embarrassed, she was taken to her gate in a wheelchair.
Three months later, she experienced another flare-up. While giving a live television interview about a short film she had made on living with MS, she suddenly lost her ability to speak.
"It was as if my mouth was packed with marbles," she said. "I kept trying to say, 'I'm sorry,' to the reporter, but nothing came out that made sense."
The medication she was taking to prevent these attacks was losing its effect, so her doctor suggested she switch to Tysabri, one of the newer, more potent "disease-modifying drugs," which reduce the severity and frequency of relapses. She also began taking Ampyra, which early last year became the first drug approved to treat any MS symptom. She hasn't had a flare-up since.
After decades of basic research on MS, the past five years have brought a rapid rollout of new and sophisticated drugs that are changing how this disease is managed and offering patients new hope.
"We have a disease that's gone from having no treatments 20 years ago to having multiple treatment options," said Dr. Timothy Coetzee, the chief research officer at the National Multiple Sclerosis Society. "There is a growing recognition that MS is becoming a manageable disease."
In MS, the body's immune system damages neurons in the brain and spinal cord, attacking the myelin sheath that insulates these nerves. About 85 percent of patients start out with what is called relapsing-remitting MS, characterized by flare-ups or attacks that cause lesions to form on the brain and that affect the ability to walk, to see and to control the bladder, among other neurological impairments.
These attacks are short-lived, and patients typically recover from them. But more than half of patients eventually develop a progressive form of MS, causing the permanent loss of these functions.
Doctors can now choose from eight disease-modifying drugs, which reduce relapses and thereby slow the progression of the disease. Some of the drugs also prevent brain neurons from dying off, now thought to be a major cause of permanent disability.
There have also been advances in treating specific symptoms of MS. Within the past two years, three medicines have been approved specifically for MS symptoms: Ampyra to improve walking, Nuedexta for uncontrollable laughing or crying, and Botox for urinary incontinence and spasticity in upper limbs.
"We're shooting for disease-free status, where someone with MS is on a medicine and has no sign of MS," said Dr. Richard Rudick, director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.
The first generation of MS drugs included mostly immune-suppressing interferons delivered via injection or infusion. These are still the most widely used, reducing relapses by about one-third. The new drugs are more sophisticated, targeting specific molecules involved in the disease, rather than simply tamping down the immune system to reduce inflammation in the brain.
Just last year, the first oral drug for MS, Gilenya, gained approval with data showing it cut the relapse rate by 55 percent. Gilenya causes inflammatory cells called lymphocytes to get trapped in lymph nodes so they don't travel to the brain, where they would damage neurons.
Patients need to be monitored for several potentially serious side effects, including a slowed heart rate and liver and vision problems. One patient recently died 24 hours after starting on Gilenya; the Food and Drug Administration is investigating the cause of the death.
The most potent drug, Tysabri, reduces the relapse rate by about 70 percent, but it comes with a small risk of a fatal brain infection caused by a common virus. Patients may be screened for antibodies to the virus; the risk of infection is considered quite low in those with no sign of the antibodies, and they are given the drug.
At least four other drugs with different mechanisms are in Phase 3 clinical trials and could win approval within the next year, experts say. Some work by protecting nerves from damage.
"There's a lot of focus on developing drugs that inhibit or stop this neurodegeneration, which we believe is the underlying cause for difficulty walking, leading people to require a wheelchair," Rudick said.
One of the new neuroprotective drugs, called BG-12, captured wide attention at an annual international conference on MS in Amsterdam in October. Researchers reported a 53 percent reduction in relapses in patients taking it and a greater than 30 percent reduction of permanent disability progression over a two-year period. It also appears to have fewer risks than equally potent drugs like Gilenya.
"This might be the drug that would completely displace the interferons," said Dr. Timothy L. Vollmer, director of neurology clinical research at the University of Colorado.
Although many doctors start patients on interferons first because of lower risks, there is a growing recognition that treating patients aggressively and early with the newer medications can preserve brain neurons and possibly prevent the progression of the disease.
But treating MS is still difficult. Many treatments come with serious side effects and other risks, and some people simply don't respond to them. Patients progress at different rates, and the symptoms vary from one patient to another. Some people cannot tolerate certain medications.
"The biggest frustration is the huge uncertainty," said Dr. Jerome J. Graber, an assistant professor of neurology at Montefiore Medical Center in New York. "I still can't predict who will progress and what's the best way to treat someone."
Still, some patients are beginning to see a more hopeful prognosis. After Salerno Kent started taking Tysabri and Ampyra, her walking improved enough for her to go hiking with husband and son, her speech issues resolved, and she felt much more confident when singing on stage.
"We have so many more options now, and I realize that we no longer have to give up the quality of life because we have MS," she said. "We've always expected to deteriorate with time, but I realize that this is not acceptable anymore."