Ruan Multiple Sclerosis Center Projects
The Ruan Multiple Sclerosis Center was the recipient of our 2003 research funding campaign. Drs. Bruce Hughes, Michael Jacoby and Michael Kirby are using the funds donated by the MARS Foundation to begin a safety study of a promising new class of MS drugs. A very early, Phase I clinical trial of a non-antibiotic tetracycline that acts as a specific enzyme inhibitor of members of the class of enzyme known matrix metalloproteinases (MMP's) will begin in early 2005. Phase I trials are essentially the first human clinical studies conducted following evaluation of extensive animal research studies. The study of this new tetracycline drug represents the first time this drug has been examined in multiple sclerosis patients and will be one of the first few studies of the drug in human subjects. The potency of this drug as an inhibitor of MMP-9 and MMP-2 (two types of MMP), combined with the lack of non-antibiotic activity and long half-life in the bloodstream (19 hours), denote this drug as a unique candidate among potential therapeutics of this category.
What MMP's do in MS
Inhibiting or blocking MMP's during an exacerbation or relapse in patients with relapsing-remitting MS is an important new area of therapeutic potential. MMP's are used in a variety of ways by cells in the body for both beneficial and destructive purposes and usually exist in an inactive form (called a proenzyme or zymogen). A small initial signal to the immune system can trigger a cascade of MMP activity, which in turn activates more MMP activity. One of the prime culprits in amplifying the MMP cascade is MMP-2. In an MS relapse or exacerbation, MMP-9 is used by immune cells (mostly T-lymphocytes) in the blood to cut through the blood vessels and allow immune cells to enter the brain. MMP-9 is one of the main end enzymes in the MMP cascade and contributes substantially to nervous system damage in MS.
Immune cells allowed into the brain by MMP-9 activity damage neurons and myelin-producing cells, and overactivate other cells in the brain which produce cell toxins (microglial cells and astrocytes). MMP-9 also is active in damaging myelin-producing cells, the myelin fragments of which serve to further activate the immune system to attack the brain. Therefore, blocking MMP's at the beginning of a relapse is of obvious great importance in restricting T-lymphocytes and other immune cells from causing nervous system damage.
When approval from the Food and Drug Administration is awarded, the project will enroll 40 volunteer patients and will be conducted over a 56-day period in a double-blind, placebo-controlled manner. A variety of safety measures will be assessed, including EKG, blood cell counts and blood chemistry, thyroid function, and skin reactions monitoring. It is hoped that this early trial will demonstrate the safety of this class of tetracyclines and lead to subsequent efficacy trials toward labeling and approval for prescription use.