About 400,000 people in the United States are affected by multiple sclerosis (often referred to by the acronym MS), an autoimmune disorder in which rogue immune cells attack the insulating layer surrounding many nerve cells in the central nervous system. Some 200 new cases are diagnosed every week in the U.S.
I wrote a while back about a study by Paul Bollyky, MD, PhD, showing that blocking production of a naturally made substance in the body could potentially protect against type 1 diabetes, another autoimmune disorder in which the body’s immune system attacks the pancreas’s insulin-producing cells (the only place where insulin is made). It now appears possible that the same drug Bollyky’s team used to achieve that benefit may also be beneficial in MS.
The substance in question — hyaluronan, a hefty, complex carbohydrate substance — is usually present at trace concentrations in the extracellular matrix that pervades all tissues and, among other things, helps glue those tissues’ constituent cells together. Intriguingly, hyaluronan levels spike markedly at the site of an injury. If you twist your ankle or stub your toe, the swelling you see afterwards is mainly due to hyaluronan, which is prone to soaking up water. That causes fluid buildup, aka swelling, in the injured region — a cardinal feature of inflammation, along with heat, redness and pain.
In a new study published in Proceedings of the National Academy of Sciences, Bollyky and his colleagues show that hyaluronan also abounds in sites of autoimmune attack in MS patients’ brains after they induced a mousie version of MS in laboratory mice. They confirmed that hyaluronan likewise accumulates near the mice’s MS lesions. And they showed that blocking new hyaluronan synthesis in the mice before symptoms developed prevented many of the mice from succumbing to MS and delayed disease onset and severity in those who did get it, while — importantly — blocking hyaluronan synthesis after symptoms developed alleviated those symptoms.
Perhaps most interesting of all: The drug they used to do that is already on the market for other indications.
In my news release on the first study, about type 1 diabetes, I wrote:
[H]ymecromone, or 4-methylumbelliferone (4-MU for short) … prescribed in many European and Asian countries for painful, gallstone-associated spasms and sold by about 60 companies worldwide for research purposes … inhibits hyaluronan synthesis. It is inexpensive, can be given orally and, over four decades of use, has what Bollyky has described as an “extremely boring safety profile”: a very low rate of associated adverse events. “It’s even approved in Europe for kids,” he said. (The Food and Drug Administration has not licensed 4-MU for any indication in the United States.)
“Considering that 4-MU is currently an approved therapeutic throughout Europe and Asia, we … propose that 4-MU treatment has great promise for the treatment of MS,” Bolloky and his colleagues write in the study. They go on to suggest that the drug may also work in “other autoimmune diseases where [hyaluronan] has been implicated in disease progression,” a list that includes not only type 1 diabetes but rheumatoid arthritis.
There’s clearly a lot of new life kicking around inside those old drugs.
Previously: Can a safe, cheap pill prevent type 1 diabetes?, Bad actors: Viruses, pathogenic bacteria star in health-horrific biofilms, Found: Potential new way to predict some multiple-sclerosis patients’ disease course, drug response and Two different types of MS, one big step toward personalized medicine
Photo by paul bica