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RandomFactor writes:

Research published in the journal Protein and Cell shows a combination of two experimental drugs reversing the effects of osteoarthritus in rats (as well as in human cartilage cell cultures).

"What's really exciting is that this is potentially a therapy that can be translated to the clinic quite easily," says Juan Carlos Izpisua Belmonte, lead author and a professor in Salk's Gene Expression Laboratory. "We are excited to continue refining this promising combination therapy for human use."

Affecting 30 million adults, osteoarthritis is the most common joint disorder in the United States and its prevalence is expected to rise in coming years due to the aging population and increasing rate of obesity. The disease is caused by gradual changes to cartilage that cushions bones and joints. During aging and repetitive stress, molecules and genes in the cells of this articular cartilage change, eventually leading to the breakdown of the cartilage and the overgrowth of underlying bone, causing chronic pain and stiffness.

This could be welcome news indeed for the 630 Million people worldwide (15% of the population) that suffer from the condition, and whose only options now are pain relievers or joint replacement surgery.

Previous research had pinpointed two molecules, alpha-KLOTHO and TGF beta receptor 2 (TGFβR2), as potential drugs to treat osteoarthritis. αKLOTHO acts on the mesh of molecules surrounding articular cartilage cells, keeping this extra-cellular matrix from degrading. TGFβR2 acts more directly on cartilage cells, stimulating their proliferation and preventing their breakdown.

Individually, the two molecules only moderately curb osteoarthritis. However…

The researchers treated young, otherwise healthy rats with osteoarthritis with viral particles containing the DNA instructions for making [both] αKLOTHO and TGFβR2.

Six weeks after the treatment, rats that had received control particles had more severe osteoarthritis in their knees, with the disease progressing from stage 2 to stage 4. However, rats that had received particles containing αKLOTHO and TGFβR2 DNA showed recovery of their cartilage: the cartilage was thicker, fewer cells were dying, and actively proliferating cells were present. These animals' disease improved from stage 2 to stage 1, a mild form of osteoarthritis, and no negative side effects were observed.

"From the very first time we tested this drug combination on just a few animals, we saw a huge improvement," says Isabel Guillen-Guillen, the paper's co-first author. "We kept checking more animals and seeing the same encouraging results."

Research into different approaches to administering the molecules and also into whether they can be used preventatively is ongoing.

Journal Reference

Paloma Martinez-Redondo, Isabel Guillen-Guillen, Noah Davidsohn, Chao Wang, Javier Prieto, Masakazu Kurita, Fumiyuki Hatanaka, Cuiqing Zhong, Reyna Hernandez-Benitez, Tomoaki Hishida, Takashi Lezaki, Akihisa Sakamoto, Amy N. Nemeth, Yuriko Hishida, Concepcion Rodriguez Esteban, Kensaku Shojima, Ling Huang, Maxim Shokhirev, Estrella Nuñez-Delicado, Josep M. Campistol, Isabel Guillen-Vicente, Elena Rodriguez-Iñigo, Juan Manuel Lopez-Alcorocho, Marta Guillen-Vicente, George Church, Pradeep Reddy, Pedro Guillen-Garcia, Guang-Hui Liu, Juan Carlos Izpisua Belmonte. αKLOTHO and sTGFβR2 treatment counteract the osteoarthritic phenotype developed in a rat model. Protein & Cell, 2020; DOI: 10.1007/s13238-019-00685-7

Original Submission