This story reveals a very important research development that could shed light on the critical question of how and why multiple sclerosis develops (or at least one version of it), and more importantly, how to effectively treat it.

Biogen's Daclizumab has recently surprised researchers with its method of action. Daclizumab, known in the market as Zenapax, is a drug currently used to prevent the rejection of organ transplants, particularly the kidney. It is now being put through Phase II (dosing) trials for multiple sclerosis. When they started the trials, researchers proposed the following hypothesis as to why it might be effective as an MS therapy:

"Interleukin-2 is a natural substance in the body that is necessary for the growth of T-lymphocytes. Zenapax is a genetically engineered antibody that blocks the activity of interleukin-2 and thus interferes with the growth of lymphocytes. Therefore, Zenapax may prevent some of the damage to myelin that occurs in multiple sclerosis."

Remember, in the auto-immune theory of multiple sclerosis, T-lymphocytes are the class of cells often supposed to be the immune system component that has "gone awry" to inadvertently attack myelin.

However, preliminary results in MS patients showed that the drug did not suppress T-cell activity as expected.

"We monitored T-cell function in patients who were injected with the drug, expecting to see that the drug inhibited T-cell function," says Dr. Bielekova.

"We didn't see that at all. To our surprise the T-cells were functioning normally."

The surprise was the fact that daclizumab therapy actually increased the activity of another component of the immune system's natural "killer" cells that are generally targeted at viruses and cancers, and generally only arise in rare circumstances, such as pregnancy (which is another period of quiescent MS activity...). Additionally, the greater the enhancement to this portion of the immune system, the better outcome the patient experienced!

"Not only did the number of regulatory natural killer cells increase in patients treated with daclizumab," says Dr. Bielekova, "but that expansion correlated with the treatment outcome--the more these cells expanded, the better the MS patients did during the trial. And the longer the patients were on the therapy, the more regulatory natural killer cells they had and the better they responded to treatment."

"The best news is that natural killer cells are actually very efficient immune cells that fight viruses or cancers," says Dr. Bielekova (director of University of Cincinnati's Waddell Center for Multiple Sclerosis), "so it appears that daclizumab doesn't damage the immune system. It only shifts the emphasis of the immune reaction from T-cells to natural killer cells.

For referene, an earlier and very small, (10 person), open-label trial indeed suggested some promise: "Daclizumab was very well tolerated and led to a 78% reduction in new contrast-enhancing lesions and to a significant improvement in several clinical outcome measures."

MS is a mystery, involving a complex interplay of immune factors, and even potentially multiple distinct diseases lumped under one name (as cancer was viewed a decade ago). Different treatment modalities may work for different people-- each one of these trials, confounding as they may be in the short-term, will help unravel the overall tapestry.

One step closer.

Please click "read more" for more references, including a link to the complete Daclizumab trial result referenced and the Phase II Daclizumab clinical trial announcement.