Researchers at Oregon Health & Science University (OHSU) have developed a compound that stimulates repair of the protective sheath that covers nerve cells in the brain and spinal cord. They suggest that the discovery could be a “game changer” that provides new hope for people living with multiple sclerosis.
Their study, involving mice genetically engineered to mimic multiple sclerosis, was published recently in the journal JCI Insight.
“There are no drugs available today that will re-myelinate the de-myelinated axons and nerve fibers, and ours does that,” says Tom Scanlan, PhD, professor of physiology and pharmacology in the OHSU School of Medicine, and senior author of the study.
Co-author Dennis Bourdette, MD, chair of neurology in the OHSU School of Medicine and director of the OHSU Multiple Sclerosis Center, states that he expects it will be a few years before the compound advances to the stage of a clinical trial involving people. Yet the study provides fresh hope for patients in Oregon and beyond.
“It could have a significant impact on patients debilitated by MS,” Bourdette shares, in a media release from Oregon Health & Science University.
The discovery, if ultimately proven in clinical trials involving people, appears to accomplish two important goals, they suggest in the release:
- Myelin repair with minimal side effects: The study demonstrated that the compound – known as sobetirome – promotes remylenation without the severe side effects of thyroid hormone therapy. Thyroid hormone therapy has not been tried in people because chronic elevated exposure known as hyperthyroidism harms the heart, bone, and skeletal muscle.
- Efficient delivery: Researchers developed a new derivative of sobetirome (Sob-AM2) that penetrates the blood brain barrier, enabling a tenfold increase in infiltration to the central nervous system.
“We’re taking advantage of the endogenous ability of thyroid hormone to repair myelin without the side effects,” comments lead author Meredith Hartley, PhD, an OHSU postdoctoral researcher in physiology and pharmacology.
Scanlan originally developed sobetirome as a synthetic molecule more than 2 decades ago, initially with an eye toward using it to lower cholesterol. Six years ago, Bourdette suggested trying the compound to repair myelin in MS.
The team then turned to Ben Emery, PhD, an associate professor of neurology in the OHSU School of Medicine, who genetically engineered a mouse model to test the treatment.
Via a chemistry process called prodrug strategy, the team then increased the amount of sobetirome that penetrated into the central nervous system.
Scientists added a chemical tag to the original sobetirome molecule, creating an inert compound called Sob-AM2. The tag’s main purpose is to eliminate a negative charge that prevents sobetirome from efficiently penetrating the blood-brain barrier. Once Sob-AM2 slips past the barrier and reaches the brain, it encounters a particular type of brain enzyme that cleaves the tag and converts Sob-AM2 back into sobetirome, the release explains.
Researchers found that the treatment in mice not only triggered myelin repair, but they also measured substantial motor improvements in mice treated with the compound.
“The mouse showed close to a full recovery,” Scanlan comments.
Scientists suggest that the compound could translate from mice to people. To that end, OHSU has licensed the technology to Llama Therapeutics Inc, a biotechnology company in San Carlos, California. Llama is working to advance these molecules toward human clinical trials in MS and other diseases.
Bourdette notes even though it may not help his patients today, he’s optimistic the discovery eventually will move from the lab into the clinic.
“Right now, what it means is hope,” he concludes.
[Source(s): Oregon Health & Science University, EurekAlert]