A molecule that inhibits the formation of critical myelin in the central nervous system may be a new therapeutic target in multiple sclerosis (MS), speculate researchers who published a study recently on their findings.1
Protecting Myelin from a Damaging Molecule
The molecule is known as LINGO-1, which researchers in Cambridge, Massachusetts discovered early last year.2 The scientists, who published both studies, say LINGO-1 is part of a host of molecules within myelin, the fatty sheath that insulates nerve fibers in the brain and spinal cord and is the main target of destruction in the pathology of MS. The molecules primarily prevent myelin and nerve fibers from being repaired after they've been damaged.
In this study, blocking the molecule in cell cultures resulted in boosted myelin formation, the research team reported.
Multiple sclerosis is a chronic, potentially debilitating disease that primarily involves the brain and spinal cord. Medical experts suspect it is an autoimmune disease; for some reason, the immune system attacks parts of the body as if they were foreign disease-causing organisms. In MS, the body incorrectly directs antibodies and white blood cells against proteins in myelin, resulting in inflammation and its eventual destruction. Eventually, the damage slows or blocks the nerve signals that control muscle coordination, strength, sensation, and vision.3
Does Blocking LINGO-1 Protect Myelin?
In their study, Sha Mi, PhD, in the department of Discovery Biology at Biogen Idec, a biotechnology company in Cambridge, and her colleagues disabled the complex of molecules in which LINGO-1 is located and found that myelin and nerve fiber regrowth resumed. They observed the molecules' activity in myelin-making cells known as oligodendrocytes taken from the brains of rats.
The scientists also compared mice that had the molecule to mice bred so that the gene for the molecule was deleted, meaning LINGO-1 itself was also absent in this second group. They found that the mice without LINGO-1 experienced more myelin production surrounding nerve fibers compared to those animals with the molecule.
These findings "indicate that LINGO-1 signaling may be critical for central nervous system myelination," Mi and her team concluded.
Another Potential Treatment Target
Earlier this year, Mi and her colleagues published the findings of a similar in-vitro study.4 They showed that another molecule can serve as a substitute, if needed, in this molecule complex that prevents myelin repair. Mi's group found that mice that lacked this substitute molecule, known as TAJ, fought off the other molecules' attempts to inhibit myelin regeneration.
The Move Toward Human Trials
So far, these findings haven't been tested in clinical trials involving humans. But the National Multiple Sclerosis Society reports it has recently established an initiative to expedite the process of developing clinical trials based on in vitro studies such as these.
A task force has been formed to study the best options to move basic research into clinical trials. The committee determined recently that one of the best ways to accomplish this is to bring together clinical specialists and basic laboratory scientists to form collaborations with that goal.
"Leading researchers now believe that treatments aimed at protecting nerves and rebuilding myelin and damaged nerve fibers are on the horizon," the society states.
1. Mi S, Miller RH, Lee X et al. LINGO-1 negatively regulates myelination by oligodendrocytes. Nat Neurosci 2005 Jun;8(6):745-51. Epub 2005 May 15.
2. Mi S, Lee X, Shao Z et al. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci 2004 Mar;7(3):221-8. Epub 2004 Feb 15.
3. Mayo Foundation for Medical Education and Research. Multiple Sclerosis. Available at: http://www.mayoclinic.com/invoke.cfm?id=DS00188. Accessed June 24, 2005.
4. Shao Z, Browning JL, Lee X et al. TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration. Neuron 2005 Feb 3;45(3):353-9.
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.
