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Epilepsy drug shows promise in slowing joint degeneration in osteoarthritis

Date:
January 3, 2024
Source:
Yale University
Summary:
Researchers have identified a drug target that may alleviate joint degeneration associated with osteoarthritis, a debilitating condition that afflicts as many as 30 million people in the United States alone. Pain relievers and lifestyle changes, such as exercise and reduced excess weight, have long been the therapies most commonly used to treat the joint stiffness and pain caused by degenerative disease, but there is a pressing need for therapies that can prevent joint breakdown that occurs in osteoarthritis.
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Yale researchers have identified a drug target that may alleviate joint degeneration associated with osteoarthritis, a debilitating condition that afflicts as many as 30 million people in the United States alone, which they report on Jan. 3 in the journal Nature.

Pain relievers and lifestyle changes, such as exercise and reduced excess weight, have long been the therapies most commonly used to treat the joint stiffness and pain caused by degenerative disease, but there is a pressing need for therapies that can prevent joint breakdown that occurs in osteoarthritis.

It is known that specialized proteins known as sodium channels found in cell membranes produce electrical impulses in "excitable" cells within muscles, the nervous system, and the heart. And in previous research, Yale's Stephen G. Waxmanidentified the key role of one particular sodium channel, called Nav1.7, in the transmission of pain signals.

Now, the labs of Chuan-Ju Liu, the Charles W. Ohse Professor of Orthopedics, and Waxman, the Bridget M. Flaherty Professor of Neurology and professor of neuroscience and pharmacology, both at Yale School of Medicine, have found that the same Nav1.7 channels are also present in non-excitable cells that produce collagen and help maintain the joints in the body.

Osteoarthritis, the most common form of arthritis, is a degenerative disease caused by the breakdown of cartilage that eases friction between the joints. It occurs most commonly in the hands, hips, and knees.

In the new study, the researchers deleted Nav1.7 genes from these collagen-producing cells and significantly reduced joint damage in two osteoarthritis models in mice.

They also demonstrated that drugs used to block Nav1.7 -- including carbamazepine, a sodium channel blocker currently used to treat epilepsy and trigeminal neuralgia -- also provided substantial protection from joint damage in the mice.

"The function of sodium channels in non-excitable cells has been a mystery," Waxman said. "This new study provides a window on how small numbers of sodium channels can powerfully regulate the behavior of non-excitable cells."

"The findings open new avenues for disease-modifying treatments," added Wenyu Fu, a research scientist in the Liu laboratory and first author of the study.


Story Source:

Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.


Journal Reference:

  1. Wenyu Fu, Dmytro Vasylyev, Yufei Bi, Mingshuang Zhang, Guodong Sun, Asya Khleborodova, Guiwu Huang, Libo Zhao, Renpeng Zhou, Yonggang Li, Shujun Liu, Xianyi Cai, Wenjun He, Min Cui, Xiangli Zhao, Aubryanna Hettinghouse, Julia Good, Ellen Kim, Eric Strauss, Philipp Leucht, Ran Schwarzkopf, Edward X. Guo, Jonathan Samuels, Wenhuo Hu, Mukundan Attur, Stephen G. Waxman, Chuan-ju Liu. Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis. Nature, 2024; DOI: 10.1038/s41586-023-06888-7

Cite This Page:

Yale University. "Epilepsy drug shows promise in slowing joint degeneration in osteoarthritis." ScienceDaily. ScienceDaily, 3 January 2024. <www.sciencedaily.com/releases/2024/01/240103130830.htm>.
Yale University. (2024, January 3). Epilepsy drug shows promise in slowing joint degeneration in osteoarthritis. ScienceDaily. Retrieved February 23, 2024 from www.sciencedaily.com/releases/2024/01/240103130830.htm
Yale University. "Epilepsy drug shows promise in slowing joint degeneration in osteoarthritis." ScienceDaily. www.sciencedaily.com/releases/2024/01/240103130830.htm (accessed February 23, 2024).

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