Multiple sclerosis remains a cruel medical mystery. It strikes in the prime of life and runs an unpredictable course that can end in total disability. Scientists are a long way from halting the disease entirely, but several promising drugs are in late-phase clinical trials and experts anticipate better lives for patients in the near future.
"We will see many new drugs on the market and many new options for patients," says Dr. Diego Centonze, a neurologist at Tor Vergata University in Rome, who is running clinical trials for three new experimental compounds, including one called fingolimod that is the first oral MS drug to move to Phase 3 clinical trials.
In the early 1990s, there were no Food and Drug Administration-approved therapies for MS on the market. Today, there are at least half a dozen, and Centonze expects as many as eight or nine by 2010.
But there are still many challenges, says Dr. Ari Green, assistant director of the multiple sclerosis center at UC San Francisco, which also is running drug company-sponsored trials. None of the approved drugs is ideal, and each of the new experimental drugs has significant adverse side effects.
MS is an autoimmune disease: The body's immune system attacks some of its own tissues. The common form, known as relapsing-remitting, begins when disease-fighting lymphocytes launch an attack on the brain and spinal cord. These relapses cause short-term inflammation and symptoms such as numbness, but eventually lead to a progressive decline of the nervous system.
The less common form of MS -- primary progressive -- doesn't manifest itself with acute attacks, although patients still exhibit neurodegeneration, leading to fatigue, pain, problems with walking and balance, dizziness and bladder and bowel dysfunction.
Currently approved drugs primarily work by reducing the activity of lymphocytes or reducing their ability to travel from the blood into the nervous system. Some of the new ones do that too -- while others function in different ways.
The first drugs to gain approval in the mid-1990s were interferon beta-1b (Betaseron), interferon beta-1a (Avonex or Rebif) and glatiramer acetate (Copaxone). Because they have minimal side effects (such as flu-like symptoms) they are used as a first line of defense. But they are only moderately effective, says Dr. Rhonda Voskuhl, director of the UCLA multiple sclerosis program. Patients "fail them, and then move on" to more powerful drugs such as natalizumab (Tysabri) and mitroxantrone.
