Posted on 02/01/2022 5:35:25 AM PST by Red Badger
The left image shows a knee joint in a healthy rat. (White indicates cartilage.) The second image from the left shows a joint with grade 2 untreated osteoarthritis. The third image shows a joint with osteoarthritis that has worsened from grade 2 to grade 4 after six weeks of placebo therapy. The right image shows a joint with osteoarthritis that improved from grade 2 to grade 1 (mild) after six weeks of combination therapy with alphaKlotho and sTGFbR2. Credit: Salk Institute
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A combination of two previously studied osteoarthritis drugs works better than either drug alone.
People with osteoarthritis, or “wear and tear” arthritis, have limited treatment options: pain relievers or joint replacement surgery. Now, Salk researchers have discovered that a powerful combination of two experimental drugs reverses the cellular and molecular signs of osteoarthritis in rats as well as in isolated human cartilage cells. Their results were published in the journal Protein & Cell on January 16, 2020.
“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.”
“From the very first time we tested this drug combination on just a few animals, we saw a huge improvement.” — Isabel Guillen-Guillen
Affecting 30 million adults, osteoarthritis is the most common joint disorder in the United States and its prevalence is expected to rise in the 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.
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.
While each drug alone had only moderately curbed osteoarthritis in animal models of the disease, Izpisua Belmonte and his colleagues wondered if the two drugs would act more effectively in concert.
“We thought that by mixing these two molecules that work in different ways, maybe we could make something better,” says Paloma Martinez-Redondo, a Salk postdoctoral fellow and co-first author of the new study.
The researchers treated young, otherwise healthy rats with osteoarthritis with viral particles containing the DNA instructions for making 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, also a Salk postdoctoral fellow and the paper’s co-first author. “We kept checking more animals and seeing the same encouraging results.”
“We think that this could be a viable treatment for osteoarthritis in humans.” — Pedro Guillen
Further experiments revealed 136 genes that were more active and 18 genes that were less active in the cartilage cells of treated rats compared to control rats. Among those were genes involved in inflammation and immune responses, suggesting some pathways by which the combination treatment works.
To test the applicability of the drug combination to humans, the team treated isolated human articular cartilage cells with αKLOTHO and TGFβR2. Levels of molecules involved in cell proliferation, extra-cellular matrix formation, and cartilage cell identity all increased.
“That’s not the same as showing how these drugs affect the knee joint in humans, but we think it’s a good sign that this could potentially work for patients,” says Martinez-Redondo.
The research team plans to develop the treatment further, including investigating whether soluble molecules of the αKLOTHO and TGFβR2 proteins can be taken directly, rather than administered through viral particles. They also will study whether the combination of drugs can prevent the development of osteoarthritis before symptoms develop.
“We think that this could be a viable treatment for osteoarthritis in humans,” says Pedro Guillen, director of the Clinica CEMTRO and co-corresponding author.
Or you can just take turmeric everyday. 🤔
For those of us just starting to get the 'aches and pains', 'masking the problem' is just fine....
Try the carnivore diet. It’s been shown to reduce inflammation. I’m 74 and have been on it four years. I was starting to get arthritis in one of my little fingers. It has not progressed, and the sharp pains are gone.
My wife would benefit. She’s had one knee replaced already. I’ve been bugging her to get the other one done.
My fingers could use it.
Agreed! Makes me wanna go, “hmmmmm”.
Me too. Where’s the downside though, kills the liver with prolonged use or shuts other systems down?
AS with so many things in life, it turns out that grandma knew what she was talking about, as she took a tablespoon every day. Grandma and Grandpa lived to 99 years.
Cod liver oil plus coQ10 will help and show improvement in about six weeks.
Best cod liver oil found to date...
Nordic Naturals
...no fish burps two hours later =o)
difficult to find lately. Amazon sold out.
Recently found, ordered and received from here;
https://www.vitacost.com/nordic-naturals-arctic-cod-liver-oil-750-mg-180-softgels
...that is all
I hate when that happens, worse when you slip through the tracks of a snow groomer and kneecap yourself.
Hold the presses, Tom Brady might not retire after all.
Get boosted multiple times.
LOL!...............
Both of my shoulder are shot after a career as an electrician, my rheumatologist said that compared to hip or knee replacement the technology for shoulder replacements are stuck in 1960 / 70s technology, this would be helpful if developed.
Me too, but if this is going to restrict joint replacement and other remedies (and the gravy train they provide sectors of the medical community) watch this be filed under “yea, so?”
“Man this would be great. I have it in hips and knees”
Hands for me.
Per the article this appears to be some sort of gene therapy.😳
“Please consider taking boron until then”
Costco has a version with Boron 5mg, 110 pills for $24. In store or on-line with free shipping (at least that is what I’m seeing for So Cal.) They use Boron glycinate, no idea if that makes a difference pro or con. I went ahead and bought some today, will give two pills a day a shot for 7 weeks and see where my achy shoulder is at after that.
Swanson Triple Boron Complex (2 cents a 3 mg boron capsule):
https://smile.amazon.com/gp/aw/d/B077HYBYLK
There's a similar one from TwinLabs called Tri-Boron, but it's fairly more expensive.
Swanson Boron from Albion Boroganic Glycine is another option I've taken (8 cents per 6mg boron capsule):
https://smile.amazon.com/gp/aw/d/B07RDYNJC5
However, the calcium fructoborate is the one most OA studies used. I do believe these ones mentioned above provide a similar benefit, but if not, you could always get the calcium fructoborate (the expensive form).
One more thing: Eggshell Membrane may be a better choice than normal glucosamine/chondroitin supplements. It has those in it, but other factors that appear to help, too.
It appears the CU-ll collagen in the Boron combo supplements is what really drives the price up. No money savings buying CU-ll and Boron separately. Wondering if the CU-ll actually is effective?
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