For the treatment of multiple sclerosis (MS), there are two main classes of medications—those that directly treat the underlying disease process and those that treat the symptoms, such as fatigue or muscle stiffness, that are caused by the disease. The FDA-approved medications for directly treating the disease, known as disease-modifying medications, are now only available in forms that must be given with a needle.
The four most commonly used medications, glatiramer acetate (Copaxone) and interferons (Avonex, Betaseron, Rebif), are administered under the skin (subcutaneous) or into the muscle (intramuscular).
The other two medications, natalizumab (Tysabri) and mitoxantrone (Novantrone), are given intravenously. There have been multiple attempts to develop non-needle ways to administer Copaxone or interferons, such as pills, inhalation, and skin patches—to date, these attempts have, unfortunately, been unsuccessful.
Oral Drugs in Development
Pills - There is now hope that some type of disease-modifying medication may be available in pill form in the future. It is notable that, in a disease where many of the newer drugs are given intravenously, there is now a wave of oral drugs that are in development. This is welcome information for all in the MS community, especially those with MS who have a difficult time tolerating injection-based medications. The oral medications in development include:
-Fingolimod (FTY 720) - In the 1990’s, Asian scientists conducted studies on mushrooms used in traditional Chinese medicine to determine whether these mushrooms contained any chemical compounds that had effects on the immune system. Through these studies, they identified a compound which has now been developed into a promising oral drug for MS.
This drug prevents immune cells from leaving lymph nodes—this mechanism, which is different from that of any existing MS drug, traps disease-causing immune cells in the lymph nodes, thereby protecting the nervous system from these cells. In clinical studies, Fingolimod has significantly decreased the frequency of MS attacks and the development of new MRI lesions. The drug is now in a large, 2,000-patient, worldwide clinical trial, known as the FREEDOMS Trial—positive results in this trial could lead to FDA approval.
-Teriflunomide - Teriflunomide is a drug that inhibits the synthesis of a chemical known as pyrimidine. Through this process, the drug regulates the activity of the immune system. It produces therapeutic effects in the animal model of MS and in rheumatoid arthritis, another immune system disease. In people with MS, teriflunomide produced beneficial effects on MRI lesions and on disability. Further studies of this drug are currently underway.
-Cladribine - Cladribine was initially developed in the 1980’s as a cancer chemotherapy drug. It may be an effective therapy for several forms of leukemia and lymphoma. It is actually FDA approved for a form of leukemia known as hairy-cell leukemia. In several early and small clinical studies of people with relapsing and progressive MS, cladribine produced clinical and MRI benefits. Due to these promising results and probable flaws in the interpretation of some previous studies, a larger trial of cladribine in people with relapsing MS is now being conducted.
-Laquinomod - Laquinomod is another promising oral drug. In the animal model of MS, this drug decreases the amount of inflammation and the severity of the disease. In a moderate-sized clinical trial of more than 200 people with MS, a high dose of the drug was shown to produce beneficial MRI effects and to be generally well-tolerated. A larger and more rigorous study is currently underway.
-Fumarate - Fumarate is a compound that is used by cells to produce energy. Through novel mechanisms, it appears to regulate immune system activity and decrease injury to nerve cells. A recent study in Europe demonstrated that fumarate decreased the development of new MRI lesions. This drug appears to be well tolerated. There are now two large worldwide clinical trials of fumarate, known as the DEFINE and CONFIRM trials.
Barroom Brawls
What does all of this have to do with barroom brawls? The nervous system injury that is caused by MS has been compared to the damage caused by a barroom brawl (see Kalb R, Holland N, Giesser B. Multiple Sclerosis for Dummies. Hoboken, NJ: Wiley, 2007).
In order for a brawl to occur, a defined sequence of events must happen (for my purposes, I will be sexist and assume that this brawl is caused by men)—angry men leave their homes, get angrier at work, go to a bar, and then get into a fight. In this sequence, the men are like immune cells that start out in lymph nodes (homes), get activated (work), and then travel to the central nervous system (the bar), where they produce injury (fight).
Among our current MS drugs, interferons and Novantrone act by decreasing the activation of the men and keeping them from entering the bar, Tysabri acts by firmly keeping the bar door closed, and Copaxone is like a bouncer who removes the men after they have entered the bar. Among the new oral drugs in development, Fingolimod acts like wives who will not let their angry husbands leave home and the other new oral drugs decrease the activation of the men and may also keep them from entering the bar.
For treating MS, and also for preventing barroom brawls, multiple points of intervention may be most effective. This new wave of oral drugs may provide novel treatment approaches that may be used alone or, perhaps more potently, in combination with our existing medications. Further studies will help guide us in using these new medications.
See Related Articles
Discover how doctors may prescribe customized treatments for MS patients individually, in MS Treatment of the Future Will Be Determined by Genes.
See New Treatment for Multiple Sclerosis? for more information about a study using beta-1a (Avonex, Rebif) or alemtuzumab (Campath, Campath-1H, MabCampath) as treatments in patients during the early stages of MS.
