Multiple Sclerosis Treatments That Show Promise Breakthroughs Include 2 Oral Medications

Multiple sclerosis, an autoimmune disease that attacks the brain and spinal cord, is insidious, causing symptoms ranging from limited movement to profound fatigue. But medical treatments that slow the progression of the disease have become available during the last 20 years, and more are in the pipeline. Below is news of the most promising emerging treatments... Multiple sclerosis (MS) affects people in the prime of their life — between ages 20 and 50 -- possibly affecting their balance, muscle coordination and their speech. “For women, this is when they are making decisions about career paths, marriage and childbearing,” says Tim Coetzee, Ph.D., chief research officer of the National Multiple Sclerosis Society. A progressive inflammatory disease, MS destroys a fatty membrane called myelin, which protects nerve fibers in the central nervous system, or brain and spinal cord. Once the myelin sheath is destroyed, the nerves’ messages are interrupted, resulting in symptoms ranging from numbness to loss of vision to paralysis. “The unpredictability of MS -- its hallmark -- can present many challenges to moving forward with their lives, not the least of which is the possibility of increasing limitations,” he says. Some, for instance, may have to reconsider their ability to care for a child or hold a job. The illness affects two to three times as many women as men, and 400,000 people in the United States, according to the National Multiple Sclerosis Society. Researchers aren’t certain why women are more prone to MS. Some speculate that genetics and female hormones may play a role, says neurologist Robert Glanzman, M.D., global development leader for ocrelizumab for Pharma Development, Hoffmann-La Roche in Nutley, N.J. Still, advancing research is putting control back in the hands of patients. “Research has enabled earlier and faster diagnosis,” Coetzee says. “This opens up opportunities for earlier treatment with disease-modifying therapies, the best way to ward off future disease activity.” “It also has led to treatments for specific symptoms, such as the ability to fight fatigue or improve walking,” he says. “Before the [FDA} approval of the first of the disease-modifying therapies – Betaseron [interferon beta- 1b] in 1993 – [doctors had] no options to modify and slow the disease from progressing,” Coetzee says. “Now we’re able to develop [disease-modifying] therapies that target particular parts of the immune system,” he says. “We’re seeing across-the-board expansion of treatment strategies, which is really good news.” Below, neurologists and researchers developing new treatments explain the most exciting MS drugs on the horizon. Multiple sclerosis treatment #1: Stem Cell Therapy The treatment helps the myelin sheath regenerate with synthetic chemicals that “turn on” a molecule called retinoid acid receptor (RXR) gamma within adult brainstem cells, says Jeffrey K. Huang, Ph.D., a lead researcher of the drug at the MS Society Cambridge Centre for Myelin Repair, University of Cambridge, England. RXR molecules help the adult stem cells transform into myelin-producing cells called “oligodendrocytes.” “For myelin to be regenerated in MS, sufficient oligodendrocytes must be available at the [damaged] area,” Huang says. Why the excitement? In MS, both the nerve fibers and cells that make myelin are damaged, but there are always immature oligodendrocyte cells that could theoretically mature and help repair myelin. That’s what happened when rodents were injected with the drug. “This was particularly exciting because it demonstrates a possible drug target for regenerative therapy in MS and a potentially novel application for known drugs [the RXR drugs] in myelin repair,” Huang says. Potential pitfalls: “RXR drugs haven’t been tested on MS patients, so it’s unclear what the side effects might be or at which stage of the disease RXR drugs would be most effective,” he says. Availability: RXR drugs, such as bexarotene (Targretin), are in clinical trials for other illnesses, such as certain cancers, Huang says. Bexarotene, for example, was approved by the Food and Drug Administration (FDA) in 1999 for treatment of T-cell lymphoma. More studies are needed before they can be considered for MS. Multiple sclerosis treatment #2: Ocrelizumab Ocrelizumab is a genetically engineered antibody that destroys B cells, a type of immune cell that drives the immune system to attack the brain and spinal cord, Glanzman says. “Many immune diseases are driven by B cells,” he explains. Why the excitement? In a 2009 Phase 2 study, MS patients saw an 80% reduction in the onslaught of immune cells attacking the myelin sheath. “Inflammatory lesions in the brain were reduced by more than 80%, and there was a significant reduction in relapses,” Glanzman says. Potential pitfalls: “We worry about any drug that [changes] the immune system, which protects the body from infection and cancer,” he says. In Ocrelizumab’s first clinical trial, one MS patient on the highest dose died, although researchers have been unable to determine why. “Her dose was three times higher than what we are using in the Phase 3 trials,” Glanzman says. “The lower dose is as effective as the highest dose in most patients. And it has resulted in no significant issues so far, although relatively few MS patients have taken the drug up to now.” Availability: Glanzman expects to file for FDA approval by the end of 2014 and launch the drug by 2015 or 2016. Multiple sclerosis treatment #3: Teriflunomide An oral medication, Teriflunomide alters the responses of immune T cells, which damage the brain and spinal cord in MS. The drug reduces inflammation and the cells’ attacks on the brain, Coetzee says. Why the excitement? In the first Phase 3 trial, Teriflunomide reduced relapse rates by as much as 31.5% and decreased the number of lesions, or scars, where immune cells have attacked the myelin sheath in the brain. It also cuts MS patients’ progression to disability by almost 30%. “Those are impressive results,” Coetzee says. “It’s different because it’s an oral medication and targets a different part of the immune pathway than other current drugs.” He foresees a time when doctors can use a combination of medications, each targeting a different part of the immune system. Potential pitfalls: It may cause liver damage, Coetzee says. The medication appears to elevate liver enzymes, which can be the result of damaged cells or inflammation, according to the Mayo Clinic. According to National Institutes of Health, the liver problems were most pronounced in patients who already had liver disease or were taking other drugs harmful to the organ. Also, “if you have to switch to another drug, you have to wait a fair amount of time before teriflunomide washes out of your system.” Researchers don’t yet know exactly how much time. Availability: “It’s still in Phase 3 clinical trials, so it will probably be a year or two before it might get FDA approval,” Coetzee says. Multiple sclerosis treatment #4: Laquinimod Laquinimod, a once-a-day oral medication, is a small, synthetic molecule that decreases cytokines, molecules secreted by immune cells that stir up inflammation and attract other immune cells to attack the brain, Coetzee explains. Why the excitement? “It turns down the production of cytokines and reduces inflammatory activity,” he says. In one of two Phase 3 trials, researchers found that it reduced relapse rates by 23%, disability by 36%, and brain atrophy, or the loss of nerve cells, by 33.8%. Also, popping a pill is more convenient and comfortable for MS patients than injecting or infusing medications. “Although patients can give themselves injections or have a loved one give them, most would prefer not to deal with the discomfort and inconvenience,” Coetzee says. “Monthly infusions require traveling to an infusion site or doctor’s office, spending a few hours out of the work day.” Oral options are important because they’re convenient and may improve compliance, he says. Potential pitfalls: Some patients had temporary, elevated liver enzyme levels, which can signal inflammation in or damage to liver cells. But Laquinimod did not lead to liver problems in the clinical trials, Coetzee says. “[It] also didn’t show as much benefit compared to a placebo as some of the other drugs did,” Coetzee says. “More data is needed to show its benefits.” Availability: The manufacturer, Teva Pharmaceutical, expects FDA approval in 2012 or 2013. Multiple sclerosis treatment #5: Alemtuzumab Alemtuzumab, a powerful antibody, destroys T and B lymphocytes immune cells, which damage the brain and spinal cord in MS patients, says Aaron Miller, M.D., medical director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at the Mount Sinai School of Medicine in New York City. Why the excitement? In a 2008 Phase 2 study, people with MS had a 74% reduction in the risk of relapse and 71% decrease in risk for disability compared with interferon beta 1-a (Rebif), an FDA-approved medication. “It’s also the only drug for MS that is annual,” Miller says. “It’s administered intravenously daily for five days, and then the patient has no more treatment for a year.” The second year the patient has only three days of treatment. Potential pitfalls: About 3% of MS patients in the Phase 3 trial developed immune thrombocytopenic purpura (ITP), a potentially serious disease that lowers the number of blood platelets necessary for clotting. About 20% of patients developed thyroid problems, such as an underactive or overactive thyroid. “Those side effects are manageable with close supervision by a physician,” Coetzee says. Also, some MS patients had an allergic-like reaction to the infusion, he says. Researchers are trying to determine who might be vulnerable. Also, because alemtuzumab alters the immune system, it opens patients to infection. Availability: The FDA has named alemtuzumab a “Fast Track Product,” meaning the FDA will try to speed its approval process. The manufacturer plans to ask for approval in 2012. Multiple sclerosis treatment #6: Daclizumab “Daclizumab antibody seems to work by expanding the number of immune cells, called natural killer cells,” Miller says. Their expansion tamps down T cells, which cause an inflammatory response in MS patients. Why the excitement? In the Phase 2 trial, daclizumab cut the relapse rate by 54%, the number of lesions detected through magnetic resonance imaging (MRI) by 69 % and the risk of disability by 57% on the lowest dose. It’s also convenient: “It’s given by injections that patients can do [themselves], one injection a month,” Miller says. That’s quite an improvement: Most injectable MS medications now have to be given three or more times a week. Potential pitfalls: As with any medication that alters the immune system, researchers are concerned about the risk of infections, Coetzee says. Availability: “Phase 3 trials are in progress,” Miller says. “So, it will probably be two to three years before it goes to the FDA for approval.” Women's Health: How Much Do You Know? There's no substitute for good health, and when it's gone, it's often gone for good.