Sobetirome: Multiple Sclerosis may have met its match

Dylan Stoll | Health Editor

Featured Image: Sobetirome, a synthetic compound, has remyelinated exposed axons in mice. | Pixabay

Multiple sclerosis (MS) is a neurodegenerative disease that affects over 2.3 million people worldwide. MS was first described as a disease by Jean-Martin Charcot, a professor at the University of Paris, in 1868, though written descriptions place MS back as far as the middle ages.

Often referred to as the father of neurology, Charcot described MS in a woman who was having tremors, slurred speech, and abnormal eye movements. After she died, he examined her brain, and found it contained the defining scars—or plaques—associated with MS.

Today, the disease has yet to be cured, but advancements have certainly been made in mitigating the effects so that those with MS can still live fulfilling and productive lives.

Dr. Christine Till, a professor at York who researches MS, explained the procedure MS patients go through when first diagnosed: “First-line treatments focus on firstly, speeding recovery following an attack; secondly, slowing or modifying progression of the disease (there are a number of medication options; selection is based on a number of factors, like severity of disease, age, cost, etc); and thirdly, managing symptoms (e.g. spasticity).”

But what causes MS? “That’s a million dollar question!” says Till,  “I don’t think anyone knows for sure, but it is presumed to involve an interplay between susceptibility genes and environmental factors, such as infectious triggers (e.g. Ebstein Barr virus) and Vitamin D. Uncovering the cause of this disease is an area of ongoing research.”

Although the exact cause is still unknown, a team of researchers from the Oregon Health & Science University (OHSU) have made a significant leap forward in the development of a cure. What they discovered was that a compound known as sobetirome—originally developed over two decades ago as a means to lower cholesterol—when modified, can repair myelin. Myelin is a fatty substance that coats and insulates nerve fibers and is one of the main focuses of MS research, as its degradation by the immune system is the reason for the characteristic MS symptoms.

When first approaching the synthetic compound sobetirome, the research team genetically modified mice to exhibit the symptoms of MS. They then used the mice to test the drug’s efficacy as a form of treatment. With promising results, they went even further, attempting to increase the amount of sobetirome that could penetrate the blood-brain barrier and enter the central nervous system.

To do this, they utilized what is known as a pro-drug strategy. What prevents sobetirome from passing the blood-brain barrier is its negative charge. By adding a chemical tag, they developed an inert version of sobetirome called Sob-AM2 that could effectively penetrate the barrier.

The genetically modified mice that were exposed to Sob-AM2 saw a significant improvement in their symptoms, achieving a nearly full recovery.

Senior author of the study Dr. Tom Scanlan, a professor of physiology and pharmacology in the OHSU School of Medicine, explained the significance of the discovery: “There are no drugs available today that will re-myelinate the de-myelinated axons and nerve fibers, and ours does that.”

Laura Wieden, the daughter of Portland advertising executive Dan Wieden, is the namesake and board member of the Laura Fund for Innovation in Multiple Sclerosis. The Laura Fund financed a good portion of Dr Scanlan and his team’s research. “I am really optimistic,” Wieden said, “I hope that this will literally be a missing link that could just change the lives of people with MS.”