Monoclonal antibodies, a type of multiple sclerosis (MS) therapy now being studied by medical researchers around the world, are therapies that have very specific effects on the body. Although findings so far are considered preliminary, international conferences are now increasingly focusing on this promising area.

To develop this MS therapy, a specific biochemical process related to a disease is identified. Antibodies, which are proteins typically made by the body to fight infections, are then made in laboratories to affect that disease-related process. If these antibodies are found to have beneficial effects, they may be made in large quantities and given intravenously.

Monoclonal Antibodies: Potential MS Drug Solutions?
In multiple sclerosis (MS), as well as in many other diseases, monoclonal antibodies are an exciting and rapidly expanding area of drug development. The first monoclonal antibody that was approved for use in MS is natalizumab (Tysabri). (Drugs that are monoclonal antibodies usually end in “-mab,” which is an abbreviated version of monoclonal antibody).

Other monoclonal antibodies with MS drug potential in development:

Alemtuzumab
Alemtuzumab, which is also known as CAMPATH, is an antibody that attacks a specific protein on immune cells.Through this process, it profoundly decreases the levels of multiple immune cells.

At a recent MS conference, investigators reported the results of a large study that compared two different doses of CAMPATH with a current MS drug, Rebif (interferon beta-1a). It was found that CAMPATH provided multiple beneficial effects. Compared to Rebif, both doses of CAMPATH had beneficial effects on MS attacks and disability.

It was noted, however, that CAMPATH increases the risk of viral infections, thyroid disease, and a serious blood-clotting disorder (idiopathic thrombocytopenic purpura, ITP)—people treated with CAMPATH must be monitored closely for these conditions.

Daclizumab
Daclizumab, also known as Zenapax, is another monoclonal antibody that is in development. By attacking an important protein called the IL-2 receptor, Zenapax decreases the levels of some immune cells (T cells) and increases the levels of other immune cells (natural killer cells).

At a recent conference, one study evaluated nearly 200 people with MS who were all treated with interferon—in addition to the interferon, people were also treated with either low-dose Zenapax, high-dose Zenapax, or a placebo. It was reported that those who received high-dose Zenapax had a 72% decrease in new MRI lesions compared to those on the placebo.

Zenapax is generally well tolerated, but there have been concerns that it, like other monoclonal antibodies, may increase the risk of people developing other immune diseases. Further studies of Zenapax as an MS therapy are underway.

Rituximab
Rituximab, also known as Rituxan, profoundly decreases the levels of an immune cell, the B cell.

At a recent MS conference, studies reported on the effects of Rituxan on people with the most common form of MS, relapsing-remitting MS, and also on people with an uncommon form of MS, primary progressive MS.

In a relatively small study of 26 people with relapsing-remitting MS, Rituxan treatment produced a decrease in attacks and also MRI activity. Although these findings are considered positive, larger and more rigorous studies of Rituxan are needed in people with relapsing-remitting MS.

People treated with Rituxan may have “infusion reactions,” which are generally mild side effects that occur when the drug is administered. In other diseases, Rituxan has very rarely been associated with PML (progressive multifocal leukoencephalopathy), which is the serious and usually fatal brain infection that has been associated with natalizumab (Tysabri).

Future of MS Therapy Approaches
As noted in the descriptions of the various monoclonal antibodies, these therapies may be very effective for MS, but they also may have serious side effects. The current commonly used MS drug spectrum, glatiramer acetate (Copaxone) and interferons (Avonex, Betaseron, Rebif), have relatively mild side effects—however, these drugs are also only partially effective.

To increase the effectiveness of whichever MS therapy is chosen, it may be necessary to use potent therapies, such as monoclonal antibodies, that have more serious side effects. In other words, to get more benefit, it may be necessary to take more risk. This certainly appears to be the case with the most recently approved MS treatment, Tysabri.

If this is indeed a growing trend in MS drug development, then it will be important for people with MS to determine for themselves, and discuss with their physicians, how much risk they are willing to take to get an increased beneficial effect.

For further information, see the MS drug research studies reported at the ECTRIMS meeting.