Yale study a potential ‘game changer’ in treating osteoarthritis
Researchers found common epilepsy drugs could protect against osteoarthritis pain and cartilage loss
A Yale University research team has made a discovery that opens an entirely new path on the treatment for osteoarthritis — commonly used epilepsy drugs could also work in reducing osteoarthritis pain and loss of cartilage.
“We call this a groundbreaking discovery,” said Chuan-Ju Liu, study author and professor of orthopedics in the Yale School of Medicine.
“This could be a new target for treating osteoarthritis.”
Osteoarthritis is the most common joint disease on earth. The U.S. Centers for Disease Control and Prevention estimates that roughly 32.5 million people have osteoarthritis. Worldwide, it is the fourth leading cause of disability.
“Osteoarthritis is a huge problem worldwide,” said Richard Miller, emeritus professor of pharmacology at Northwestern University School of Medicine in Chicago. “There are two main things, one is joint degeneration and the other is pain.”
It causes pain, swelling, joint locking and stiffness. Over time these symptoms can degenerate to disability.
The disease is caused by the slow breakdown of cartilage and joint tissues. Mechanical stress, genetic factors, insufficient cellular repair, age and body weight all contribute to the development of the disease.
People who work physically demanding jobs also have an increased risk of developing osteoarthritis.
There is no cure, but symptoms can be managed with pain relief, exercise and supportive therapy.
Miller explained that scientists around the world have been searching for a non-opioid drug that could help people with osteoarthritis.
Liu’s team discovered a promising target, one that already has drugs that work on it. It’s long been known that nerve cells rely on proteins called “sodium channels.” These proteins prime nerve cells, muscle cells and heart tissue to fire electrical pulses.
These pulses are what make muscles twitch and nerves pass signals.
Miller said the Yale research team has shown a series of experiments that suggests sodium channels are important to the biology of cartilage.
“If you inhibit (the sodium channel’s) function you will stop the degeneration of the cartilage,” he said.
Epilepsy patients frequently have sodium channels with mutations that make nerve cells over-active and more susceptible
“They’re making an enormous claim. If you have a drug that blocks Nav1.7 it will not only stop the pain in osteoarthritis, but it will also stop cartilage degeneration. … In terms of the implications for osteoarthritis, they couldn’t be bigger.” Richard Miller, Northwestern University School of Medicine
to seizures.
Drugs that target these sodium channels are used to prevent seizures in epilepsy.
Liu’s team discovered that a specific sodium channel, Nav1.7, which plays a role in epilepsy and pain-insensitivity disorders, is also expressed in human cells that produce and maintain cartilage.
They found that mice lacking Nav1.7 in either the cartilage or nerves or both, without the sodium channel in their joints, experienced less inflammation, bone spurs, and cartilage loss.
Mice that had Nav1.7, but were given blockers currently used for epilepsy, also experienced a protective effect.
“They’re making an enormous claim,” said Miller.
“If you have a drug that blocks Nav1.7 it will not only stop the pain in osteoarthritis, but it will also stop cartilage degeneration … In terms of the implications for osteoarthritis, they couldn’t be bigger.”
Liu said drugs for epilepsy could potentially be repurposed to treat osteoarthritis.
Since there are Federal Drug Administration approved drugs that already target Nav1.7, this creates a much quicker path to finding a treatment for osteoarthritis.
“What we know now is stopping the Nav1.7 channel can stop or slow down the degeneration of cartilage,” said Liu. “What we don’t know is whether blocking this will regrow cartilage.”
Miller urged caution, saying the study did not demonstrate that blocking Nav1.7 has the same effect in humans as it did in mice.
Still, he said that Liu’s paper would have scientists who study osteoarthritis “all over it.”
“It’s a bold idea. It’s clear what people would do to investigate this,” said Miller. “But there’s a huge gap that has to be filled before we know whether it actually has an effect in humans.”
Because there are already approved drugs that work on Nav1.7, Miller expects to see rapid movement into human testing.
“I think lots of people will try experiments of this now based on their claims,” said Miller.
“If it works, it’s a total game changer.”