Investigational MS Medicine Targets Immune Regulators
by John C. Martin
Article Date: 07-22-05
A drug that targets compounds that direct the movement of damage-causing immune cells in the central nervous system is about to be scrutinized in a new clinical trial. The study will test the drug, known by its code name, MLN1102, manufactured by Millennium Pharmaceuticals, as a possible treatment for multiple sclerosis.
"MS remains a significant area of unmet medical need, and we are hopeful that the novel mechanism of action of MLN1102 could provide patients with a new treatment option," said Nancy Simonian, MD, senior vice-president of Clinical, Regulatory, and Medical Affairs at Millennium.
Chemokine Receptors: Holding Them Back
The drug specifically targets certain chemokine receptors on the surfaces of a group of white blood cells known as macrophages and monocytes, blocking their action. Several preclinical studies have suggested that chemokine receptors, which are normally designed to direct certain cells of the immune system toward a disease-causing organism or infectious agents in the body, may play a key role in the inflammatory response.1,2
During the acute phase of multiple sclerosis, the activity of chemokine receptors moves into high gear, as seen in both studies of humans and animals.3,4 Apparently, these compounds direct T-cells and other white blood cells into the central nervous system, where damage to neurons and myelin occur. As such, chemokine receptors have been the target of research investigating new medicines for multiple sclerosis.
How MS Begins
MS is a disease characterized by areas of inflammation and scarring in the central nervous system. Damage occurs mostly to nerve fibers and myelin, a fatty sheath that covers and protects these nerve fibers. As a result, nerve "communication" is disrupted, and neurological impairment results.
Medical experts theorize that MS is an autoimmune disease in which, for an unknown reason, the body's immune system goes haywire, attacking normal body tissue rather than disease-causing invaders like bacteria or viruses. While MS is not an inherited disease, research has shown that it may strike people who have an increased susceptibility to autoimmune disease. It's estimated that between 350,000 and a half million people in the United States have been diagnosed with MS. The illness is more common in women and Caucasians. The large majority of patients are diagnosed between the ages of 16 and 60, though it's not uncommon for the disease to strike in early childhood or after age 60.5
Can a Drug Block Chemokine Receptor Activity?
In the phase 2, proof-of-concept study of MLN1202, about 40 patients are being enrolled. Both safety and tolerability of the drug will be scrutinized, as well as its effect on MS activity. Researchers will be conducting magnetic resonance imaging (MRI) exams to determine that. "MLN1202 is designed to specifically target the [chemokine] receptors found primarily on monocytes and macrophages, versus all leukocytes, which may be beneficial in lowering the risk of systemic immune suppression," Simonian explained.
This is potentially beneficial because a drug that would suppress the entire immune system would leave a person with MS susceptible to infections from viruses, bacteria, and the like. MLN1202, by contrast, suppresses only a small group of immune cells.
The drug is currently being evaluated in two unrelated clinical trials—one, involving patients with another autoimmune disease, rheumatoid arthritis. Additional studies to test the effectiveness of the drug in atherosclerosis and a tissue disease known as scleroderma are also being planned, Millennium stated.
1. Glabinsk AR, Ransohoff RM. Targeting the chemokine system for multiple sclerosis treatment. Curr Opin Investig Drugs 2001 Dec;2(12):1712-9.
2. Zhang GX, Baker CM, Kolson DL, Rostami AM. Chemokines and chemokine receptors in the pathogenesis of multiple sclerosis. Mult Scler 2000 Feb;6(1):3-13.
3. Muller DM, Pender MP, Greer JM. Chemokines and chemokine receptors: potential therapeutic targets in multiple sclerosis. Curr Drug Targets Inflamm Allergy 2004 Sep;3(3):279-90.
4. Kivisakk P, Mahad DJ, Callahan MK et al. Expression of CCR7 in multiple sclerosis: implications for CNS immunity. Ann Neurol 2004 May;55(5):627-38.
5. Multiple Sclerosis Foundation. MS Info. Available at: msfacts.org. Accessed July 14, 2005.
msneighborhood.com |
