Synthetic molecule shows promise as multiple sclerosis treatment
In multiple sclerosis, the body's immune system attacks and damages myelin, which is the insulating layer on nerves in the spinal cord, brain and optic nerve. This causes the nerves to short-circuit and cease functioning properly. In "a potential game-changer," scientists have now demonstrated that a synthetic molecule can restore compromised myelin.
Oregon Health and Science University's Prof. Tom Scanlan first created the sobetirome molecule over 20 years ago, as a possible means of lowering cholesterol. In 2013, his colleague Dr. Dennis Bourdette suggested that it might also be useful in the treatment of multiple sclerosis (MS).
In early lab tests performed on mice that were genetically engineered to have MS-like symptoms, sobetirome was indeed found to repair their damaged myelin. Importantly, it did so without any noteworthy side effects. By contrast, research suggests that experimental thyroid hormone therapy would harm peoples' heart, bones and skeletal muscle.
At the time of those first sobetirome trials, however, the effectiveness of the molecule as an MS treatment was restricted by its limited ability to cross the blood-brain barrier.
With that in mind, the scientists recently added a chemical tag to the molecule, creating a compound known as Sob-AM2. It eliminates a negative electrical charge that ordinarily keeps sobetirome from efficiently penetrating the barrier. Once the compound has thus passed through that barrier, a brain enzyme cleaves off the chemical tag, causing the Sob-AM2 to revert back to regular myelin-restoring sobetirome.
This strategy resulted in a tenfold increase in the amount of sobetirome that can infiltrate the central nervous system. In subsequent mouse tests, the animals showed substantial motor improvements, reportedly showing close to a full recovery.
Scanlan and Bourdette are confident that the treatment should have a similar effect on people. The university has licensed the technology to Llama Therapeutics Inc., which is now working toward human trials.
"There are no drugs available today that will re-myelinate the de-myelinated axons and nerve fibers, and ours does that," says Scanlan. It should be noted, however, that teams at Melbourne University, the University of Utah and the University of California-Riverside are all also developing medications that do so.
A paper on the research was recently published in the journal JCI Insight.