A unique compound that may help give the immune system a boost during its abnormal attack at the heart of multiple sclerosis has become a new target in research aimed at finding other treatments for the disease.
New Treatment Target?
At a recent medical conference in Boston,1 doctors from the Montreal Neurological Institute examined a compound that they claim plays a role in preventing a form of pre-programmed cell death known as apoptosis (ap-ahp-TOE-sis). Causing apoptosis in the immune system would kill off its abnormally attacking cells. Thus, preventing the action of this compound, known as XIAP, would mediate the process of immune system apoptosis, and block its destructive action at the outset of MS, in theory.
It's believed that MS may be an autoimmune disease—that it occurs because the immune system, for an unknown reason, directs its cells to go after a fatty substance in the brain and spinal cord known as myelin (MYE-uh-lin). When this substance is damaged or destroyed, the nerve cells it protects become vulnerable, and they too, get destroyed in the process. The result is manifested in the symptoms seen in MS. Some of the theories behind this aberrant process include the possibility that the immune system goes haywire due to genetics, gender (more women than men are diagnosed with the disease), and certain triggers, such as the environment, viruses, trauma or heavy metals.2
In a study using mice, Trevor Owens, PhD, and Simone Zehntner, PhD, used an intervention to block the action of XIAP, in hopes of lowering levels of the compound in immune system cells. When mice with a disease similar to MS were given the intervention once a day, eventually, their disease began to subside. In another 84% of the animals, disease progression completely stopped, the two researchers reported. In a separate group of mice not given the intervention, XIAP levels were maintained, and their disease progression increased severely, Owens and Zehntner noted. These findings were seen just 5 days after the intervention was begun, they said.
Underlying Mechanisms
How does XIAP help prevent apoptosis? At the molecular level, it inhibits an enzyme known as caspase (KAS-paze) that plays a role in immune system apoptosis. There are several classes of caspases, all of which play a role in the destruction of cells.3 In a healthy person, caspases play a beneficial role, by helping cells that serve no function or are diseased to die off. For instance, caspase destroys cancer cells before the cancer can spread.3
Thus in this case, preventing XIAP paradoxically boosts the activity of caspase and immune cells die, theoretically preventing their attack on myelin.
Human Trials Underway
Based on the positive findings from these animal studies, Aegera Therapeutics, a Canadian pharmaceutical company, is sponsoring an early phase clinical trial to test a drug designed to block the action of XIAP. The drug, using the code name AEG35156, was manufactured as a cancer therapy. By inhibiting XIAP, cancer apoptosis can theoretically continue. The drug might inhibit this compound alone or in combination with certain chemotherapeutic medications, the company has stated. Phase 1 trials involving patients were launched last year in the UK, and additional trials are currently being planned in the United States and Canada, Aegera said.
1. 5th Annual Meeting of the Federation of Clinical Immunology Societies. FOCIS 2005. 2005 May 12-16. Boston, MA.
2. National Multiple Sclerosis Society. What Causes MS? Available at: http://www.nationalmssociety.org/What%20causes%20MS.asp. Accessed June 10, 2005.
3. The Huntington's Disease Association. What is a Caspase? Available at: http://www.hda.org.uk/research/rs006.html.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
