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Study shows promise in repairing damaged myelin
April 19, 2019
Researchers at Oregon Health and Science University have developed a compound that stimulates repair of the protective sheath that covers nerve cells in the brain and spinal cord. The study’s authors said they expect it will be a few years before the compound advances to the stage of a clinical trial involving people.
The discovery involved mice genetically engineered to mimic multiple sclerosis. If ultimately proven in clinical trials involving people, it appears to accomplish two important goals:
* 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.
The authors credited the breakthrough to a collaboration that involved scientists and physicians with expertise ranging across neurology, genetics, advanced imaging, physiology and pharmacology. They did so through a trick of chemistry known as a prodrug strategy.
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.
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.
Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the study’s authors are confident that the compound will translate from mice to people.
The discovery was published in the journal
JCI Insight
.
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